Individual Overall Survival Research Articles

MiR-559 rs58450758 polymorphism is associated with colorectal cancer risk and prognosis in Chinese Han population.

Aim: This research examined the correlation between miR-559 rs58450758 and the clinical pathological characteristics and prognosis of CRC.Materials & methods: RT-qPCR was utilized to assess the miR-559 expression levels. Chi-square test was used to investigate the relationship between miR-559 and clinical features. The association between rs58450758 different genotypes and CRC risk, as well as clinical pathological parameters, was explored, utilizing logistic regression analysis and chi-square tests. The Cox regression model and Kaplan-Meier analysis evaluated overall survival in individuals with CRC.Results: The miR-559 was down-regulated in CRC patients' serum. The expressions of miR-559 were significantly associated with tumor size, differentiation, TNM stage and lymph node metastasis. The rs58450758 TT genotype and T allele carriers were more prevalent among CRC patients. The rs58450758 polymorphism was notably linked to tumor size, differentiation, TNM stage and lymph node metastasis in CRC patients. Furthermore, CC genotype carriers exhibited a longer survival period than CT/TT genotypes within the CRC population.Conclusion: The miR-559 rs58450758 polymorphism exhibits promise as a potential biomarker for prognosticating the outcomes of CRC.

Changes in the overall survival of patients with metastatic renal cell carcinoma in the era of immune-checkpoint inhibitors

BackgroundThe advent of immune checkpoint inhibitors (ICI) has brought about a significant transformation in the treatment of immunogenic tumors. On November 23, 2015, the United States Food and Drug Administration approved Nivolumab to treat metastatic renal cell carcinoma (RCC). We aimed to assess potential changes in the survival rates of patients with metastatic RCC at a population level after the approval of Nivolumab. MethodsWe used data from the latest version of the Surveillance, Epidemiology, and End Results (SEER) database which encompasses data up to the year 2020. We included patients with age ≥ 20 years who were diagnosed with ‘distant’ RCC from 2011 through 2020. Based on the approval of Nivolumab, the period from 2011 to 2020 was further grouped into 2011–2015 (pre-ICI era) and 2016–2020 (ICI era). ResultsThe median overall survival (OS) was 8 months in the pre-ICI era compared to 11 months in the ICI era (log-rank test, χ2 = 102.53, p < 0.001). Patients diagnosed with metastatic RCC in the ICI era had a significantly lower risk of dying [Cox proportional Hazard Ratio of 0.77, 95 % CI (0.74–0.80)] compared to patients diagnosed in the pre-ICI era. Additionally, patients under the age of 75 had a lower risk of death compared to those aged 75 years or older. Patients who received chemotherapy (systemic therapy), radiotherapy, or surgery faced a significantly lower risk of mortality. Individuals with metastasis to the brain, bone, liver, or lung had a significantly higher risk of death than those without metastasis to these locations. Marital status also played a role, as married individuals had a significantly lower risk of death compared to those who were divorced, separated, or widowed at the time of diagnosis. Furthermore, income level influenced survival, with patients earning a median annual household income of more than USD 75,000 exhibiting a significantly lower risk of mortality compared to those earning between USD 50,000 and USD 74,000. There was no significant difference in survival observed between non-Hispanic blacks and non-Hispanic whites. ConclusionThe advent of immune checkpoint inhibitors has led to a substantial improvement in the median overall survival of individuals diagnosed with metastatic renal cell carcinoma.

Screening high-risk individuals for primary gastric carcinoma: evaluating overall survival probability score in the presence and absence of lymphatic metastasis post-gastrectomy

ObjectiveThe aim of this study was to develop and validate prognostic models for predicting overall survival in individuals with gastric carcinoma, specifically focusing on both negative and positive lymphatic metastasis.MethodsA total of 1650 patients who underwent radical gastric surgery at Shanxi Cancer Hospital between May 2002 and December 2020 were included in the analysis. Multiple Cox Proportional Hazards analysis was performed to identify key variables associated with overall survival in both negative and positive lymphatic metastasis cases. Internal validation was conducted using bootstrapping to assess the prediction accuracy of the models. Calibration curves were used to demonstrate the accuracy and consistency of the predictions. The discriminative abilities of the prognostic models were evaluated and compared with the 8th edition of AJCC-TNM staging using Harrell’s Concordance index, decision curve analysis, and time-dependent receiver operating characteristic curves.ResultsThe nomogram for node-negative lymphatic metastasis included variables such as age, pT stage, and maximum tumor diameter. The C-index for this model in internal validation was 0.719, indicating better performance compared to the AJCC 8th edition TNM staging. The nomogram for node-positive lymphatic metastasis included variables such as gender, age, maximum tumor diameter, neural invasion, Lauren classification, and expression of Her-2, CK7, and CD56. The C-index for this model was 0.674, also outperforming the AJCC 8th edition TNM staging. Calibration curves, time-dependent receiver operating characteristic curves, and decision curve analysis for both nomograms demonstrated excellent prediction ability. Furthermore, significant differences in prognosis between low- and high-risk groups supported the models’ strong risk stratification performance.ConclusionThis study provides valuable risk stratification models for lymphatic metastasis in gastric carcinoma, encompassing both node-positive and negative cases. These models can help identify low-risk individuals who may not require further intervention, while high-risk individuals can benefit from targeted therapies aimed at addressing lymphatic metastasis.

Comparison of overall and patterns of care in patients with a malignant ovarian germ cell tumor by age in the United States: a National Cancer Database (2004–2016) analysis

BackgroundWomen aged ≥40 years diagnosed with a malignant ovarian germ cell tumor are more likely to have poor outcomes than their younger counterparts (aged 15–39 years).ObjectiveWe used the National Cancer...

Demographic and survival data of patients with primary diffuse large B-cell lymphoma of the head and neck: A single center experience.

e19069 Background: Head and neck malignancies account for around 10% of lymphomas, with diffuse large B-cell lymphoma (DLBCL) being the most prevalent histologic subtype. Head and neck lymphoma is as the second most pervasive location for extra-nodal lymphoma, following the gastrointestinal system. This study focused on examining the demographic characteristics, main localization distribution, and survival rate of patients with head and neck lymphoma at the Çukurova University Medical Oncology Clinic. Methods: We conducted a retrospective analysis of 97 individuals diagnosed with single-center, head, and neck diffuse large B-cell lymphoma (DLBCL) from 2011 to 2020. Data pertaining to patients was acquired from electronic medical records. The patients were categorized based on anatomical localization, and survival rates and survival data were computed for each primary localization. Results: Out of the total number of patients, 48 (49.5%) were female, and 49 (50.5%) were male. The patients had a median age of 59.5 years. Waldeyer's ring was the most frequent site of primary head and neck tumor localization in patients with DLBCL, accounting for 42.4% of cases. The distribution of anatomical sites was as follows: nasopharynx accounted for 30.8%, nasal cavity accounted for 10.3%, thyroid accounted for 6.2%, parotid accounted for 5.2%, oral cavity accounted for 3.9%, and other anatomical sites accounted for 1.2%. Based on the Ann Arbor staging approach, 65% of the patients were classified as stage I-II. The 3-year survival rate was 71%, while the 5-year survival rate was 61%. The overall survival of individuals with nasopharyngeal lymphoma was considerably shorter when compared to those with non-nasopharyngeal lymphomas (p=0.0372). Conclusions: We conducted a thorough analysis of the data pertaining to lymphomas characterized by diffuse large B-cell lymphoma (DLBCL) occurring in the head and neck region. The study found that when the nasopharynx is affected, it is linked to a worse prognosis and may necessitate more intensive treatment. Our work is a retrospective study conducted at a single center. However, future investigations with a more significant number of participants and a prospective design is necessary.

Is sarcopenia effective on survival in patients with metastatic gastric cancer?

Sarcopenia is a progressively diminishing state characterized by the reduction of muscle mass and density, which is frequently observed in malignancies of solid organs. To assess how sarcopenia affects the overall survival of individuals who have been diagnosed with metastatic gastric cancer. The study retrospectively included individuals who had been diagnosed with metastatic gastric cancer between January 2008 and December 2020. Sarcopenia was identified through the calculation of the average Hounsfield units (HUAC) using computed tomography (CT) images taken at the time of diagnosis in patients. A total of 118 patients with metastatic gastric cancer were evaluated. Sarcopenia was detected in 29 patients (24.6%). The median survival of all patients was 8 (1-43) mo. The median survival of patients with sarcopenia was 2 mo, while it was 10 mo for those without sarcopenia (P < 0.001). A significant relationship was found between sarcopenia and survival. Sarcopenia has been observed to impact survival outcomes in various types of solid tumor cancers. Sarcopenic patients can be identified in a short time, easily and inexpensively, by HUAC measurements from CT images used for diagnosis, and survival could be promoted with nutritional support.

Development and external validation of a nomogram for predicting overall survival of patients with non-endometrioid endometrial cancer: A population-based analysis

ObjectivesThe main objective of this study was to identify the key predictors and construct a nomogram that can be used to predict the overall survival of individuals with non-endometrioid endometrial cancer. MethodsA total of 2686 non-endometrioid endometrial cancer patients confirmed between 1988 and 2018 were selected from the Surveillance, Epidemiology, and End Results database. They were divided into a training cohort and an internal validation cohort. Independent risk factors were chosen by Cox regression analyses. A predictive nomogram model for overall survival was constructed based on above factors. A Chinese cohort of 41 patients was collected to be an external validation cohort. ResultsEight variables were estimated as independent predictors for overall survival. A nomogram was established using these factors. The C-index for predicting the overall survival of patients with non-endometrioid endometrial cancer from the nomogram was 0.734, 0.700, and 0.767 in training, internal, and external validation cohort, respectively. Calibration plots and decision curve analysis showed that the nomogram was valuable for further clinical application. ConclusionWe constructed a nomogram which can be used as an effective tool to predict the 3- and 5-year overall survival of Non-endometrioid endometrial cancer patients.

Abstract 4793: Effects of treatment delays on lung cancer survival

Abstract Background: Previous studies have established a link between treatment initiation delays and reduced overall survival in individuals diagnosed with lung cancer. These delays are often influenced by diagnostic complexities, logistical hurdles, and patient-related factors. However, the association between treatment delays and survival outcomes has yet to be extensively investigated using data from a large national cohort. This study aims to fill this research gap and provide unique insights into the relationship between treatment delays and lung cancer survival by utilizing data from a substantial national cohort. Methods: The study population consisted of 3,723 lung cancer patients participating in the NCI PLCO Cancer Screening Trial. Cox Proportional Hazards (PH) Regression analyses examined the time between cancer diagnosis and treatment initiation using several measures including intervals from tumor doubling/stage progression time models by Spratt et al. (1964) and Detterbeck et al. (2008). Analyses controlled for patient and clinical characteristics including age, sex, race/ethnicity, smoking status, histopathologic type, cancer stage, and treatment modality. Data analysis was conducted using Microsoft Excel, STATA, and IBM SPSS software. Results: PH Regression analyses demonstrated a clear association between longer time intervals from diagnosis to treatment initiation and increased risk of mortality. Patients with time intervals exceeding 20 days exhibited a hazard ratio (HR) for mortality of 1.21 (p &amp;lt; 0.001, 95% confidence interval [CI] 1.1158-1.3176). The Spratt tumor progression model, considering intervals exceeding 88 days, revealed a HR of 1.22 (p = 0.03, 95% CI 1.0146-1.4885). On the other hand, the Detterbeck model, which considered intervals exceeding 118 days, did not show a statistically significant association with increased mortality risk. Furthermore, PH analysis identified cigarette smoking status, marital status, and tumor grade as significant predictors of mortality risk. Conclusions: Data from a large national cohort study indicate that delays in lung cancer treatment initiation have detrimental impacts on survival. Treatment initiation shortly after diagnosis had the most significant differential impact on mortality risk. Timely initiation of treatment is of utmost importance and should be prioritized in lung cancer care. By addressing factors contributing to treatment delays, it is likely possible to improve the survival rates of patients with lung cancer. Citation Format: Percy Guzman Montero, Sharon Segura Cordero. Effects of treatment delays on lung cancer survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4793.

Impact of TP53, RB1, and PTEN mutations on overall survival in metastatic prostate cancer: A multi-center study via the Guardian Research Network.

82 Background: The treatment paradigm for metastatic prostate cancer has significantly improved in the past decade. Nevertheless, there remains an unmet need for novel biomarker-driven risk stratification. Studies have shown that genetic alterations in any of the PTEN, RB1, and TP53 genes influence the prognosis, potential for androgen independence and overall survival of individuals diagnosed with advanced prostate cancer. Based on these findings, we compared survival rates by contrasting patients with any of these mutations to those lacking them, using an extensive real-world sample from community oncology centers across the Guardian Research network (GRN). Methods: All patients diagnosed with metastatic prostate cancer who had undergone Next-Generation Sequencing (NGS) were included across an oncology-focused hospital consortium network database (GRN). Study participants were classified into two cohorts based on the presence or absence of biomarkers. Patients harboring at least one of the following genomic alterations— TP53, Rb, or PTEN—were categorized as "biomarker-positive." Those without these mutations were designated as "biomarker negative." Overall survival (OS) was compared between the two cohorts by Kaplan-Meier Curve analysis. Results: We identified 350 patients with metastatic prostate cancer, of which 140 were biomarker positive and 210 were biomarker negative. The biomarker-positive cohort had a lower overall survival (p=0.002) when compared to the biomarker-negative cohort. For the sub-group with a minimum follow up of four years, median survival was 35.8 months vs 67.2 months for biomarker marker positive and negative cohorts, respectively. Furthermore, the biomarker-positive cohort was associated with significantly higher number of patients with bone and liver metastases. Conclusions: Our study indicates poor overall survival in patients with TP53, RB1, and PTEN mutated prostate cancer, underscoring the need for novel treatment strategies for this aggressive disease genotype. Future studies based on genomic risk stratification are needed to customize therapies through appropriate intensification or de-intensification based on individual genomic profiles. [Table: see text]

Long-term clinical outcomes of combined modality therapy for advanced-stage Hodgkin lymphoma in the PET era: A retrospective study.

The role of consolidation radiation therapy (CRT) after complete metabolic response to chemotherapy in advanced-stage (stage III and IV) Hodgkin lymphoma (HL) is controversial. This study was undertaken to assess the clinical outcomes in terms of event free survival, local failure free survival and overall survival in individuals with advanced HL treated with chemotherapy and CRT. A retrospective review was conducted to study the long-term clinical outcomes in individuals diagnosed with HL and treated with chemotherapy and CRT from 2012 to 2016 at a tertiary cancer care hospital in India. Data from 203 study participants with advanced-stage HL were analyzed. Positron emission tomography-computed tomography (PET-CT) was done at baseline and after 2 cycles for response assessment. The median age at presentation was 32 yr [interquartile range (IQR): 26-46]. Early metabolic response (after 2 cycles) and delayed metabolic response (after 4 or 6 cycles) were observed in 74.4 and 25.6 per cent of individuals, respectively. With a median follow up of 52 months (IQR: 40-67), the five-year event-free survival (EFS), local failure-free survival (LFFS) and overall survival (OS) were 83.2, 95.1 and 94.6 per cent, respectively. On univariate analysis, extranodal disease was associated with inferior EFS (P=0.043). Haemoglobin <10.5 g/dl (P=0.002) and Hasenclever index >3 (P=0.00047) were associated with poorer OS. Relapses were observed in 28/203 (13.8%) study participants with predominance at central nodal stations. The median time to relapse was 19.4 months (IQR: 13-33). Local relapse alone (at the irradiated site) was observed in 5/28 study participants, systemic (distant) relapse in 14/28 individuals, while both systemic and local relapse was observed in 9/28 participants. Extranodal disease (P=0.05), bulky disease (P=0.005) and haemoglobin concentration ≤10.5 g/dl (P=0.036) were significant predictors for disease relapse. Individuals with advanced-stage HL treated with anthracycline-based chemotherapy (anthracycline-based chemotherapy with doxorubicin, bleomycin, vinblastine and dacarbazine regimen) and CRT had excellent long-term outcomes. As isolated infield failures are uncommon, selective consolidation with conformal RT to high-risk sites improves final disease outcomes.

LncFASA promotes cancer ferroptosis via modulating PRDX1 phase separation.

Ferroptosis, a unique type of non-apoptotic cell death resulting from iron-dependent lipid peroxidation, has a potential physiological function in tumor suppression, but its underlying mechanisms have not been fully elucidated. Here, we report that the long non-coding RNA (lncRNA) LncFASA increases the susceptibility of triple-negative breast cancer (TNBC) to ferroptosis. As a tumor suppressor, LncFASA drives the formation of droplets containing peroxiredoxin1 (PRDX1), a member of the peroxidase family, resulting in the accumulation of lipid peroxidation via the SLC7A11-GPX4 axis. Mechanistically, LncFASA directly binds to the Ahpc-TSA domain of PRDX1, inhibiting its peroxidase activity by driving liquid-liquid phase separation, which disrupts intracellular ROS homeostasis. Notably, high LncFASA expression indicates favorable overall survival in individuals with breast cancer, and LncFASA impairs the growth of breast xenograft tumors by modulating ferroptosis. Together, our findings illustrate the crucial role of this lncRNA in ferroptosis-mediated cancer development and provide new insights into therapeutic strategies for breast cancer.

Effects of treatment delays on lung cancer survival.

478 Background: Previous studies have established a link between treatment initiation delays and reduced overall survival in individuals diagnosed with lung cancer. These delays are often influenced by diagnostic complexities, logistical hurdles, and patient-related factors. However, the association between treatment delays and survival outcomes has yet to be extensively investigated using data from a large national cohort. This study aims to fill this research gap and provide unique insights into the relationship between treatment delays and lung cancer survival by utilizing data from a substantial national cohort. Methods: The study population consisted of 3,723 lung cancer patients participating in the NCI PLCO Cancer Screening Trial. Cox Proportional Hazards (PH) Regression analyses examined the time between cancer diagnosis and treatment initiation using several measures including intervals from tumor doubling/stage progression time models by Spratt et al. (1964) and Detterbeck et al. (2008). Analyses controlled for patient and clinical characteristics including age, sex, race/ethnicity, smoking status, histopathologic type, cancer stage, and treatment modality. Data analysis was conducted using Microsoft Excel, STATA, and IBM SPSS software. Results: PH Regression analyses demonstrated a clear association between longer time intervals from diagnosis to treatment initiation and increased risk of mortality. Patients with time intervals exceeding 20 days exhibited a hazard ratio (HR) for mortality of 1.21 (p &lt; 0.001, 95% confidence interval [CI] 1.1158-1.3176).The Spratt tumor progression model, considering intervals exceeding 88 days, revealed a HR of 1.22 (p = 0.03, 95% CI 1.0146-1.4885). On the other hand, the Detterbeck model, which considered intervals exceeding 118 days, did not show a statistically significant association with increased mortality risk. Furthermore, PH analysis identified cigarette smoking status, marital status, and tumor grade as significant predictors of mortality risk. Conclusions: Data from a large national cohort study indicate that delays in lung cancer treatment initiation have detrimental impacts on survival. Treatment initiation shortly after diagnosis had the most significant differential impact on mortality risk. Timely initiation of treatment is of utmost importance and should be prioritized in lung cancer care. By addressing factors contributing to treatment delays, it is likely possible to improve the survival rates of patients with lung cancer.

Malignant glomus tumor of the head and neck: A National Cancer Database analysis.

e18078 Background: Malignant glomus tumors of the head and neck are rare malignancies originating from glomus bodies found within the skin, soft tissues, and mucosa of the head and neck. Malignant glomus tumors often arise from benign glomus tumors and rarely metastasize. In cases where metastasis had ocurred it was typically fatal. Another review of the malignant glomus tumor cases indicated that only a minority developed metastases. These findings, along with a general lack of knowledge regarding demographic and socioeconomic factors on glomus tumors warrants further investigation. The National Cancer Database (NCDB) was analyzed to identify demographic factors among patients and better understand the epidemiology of these tumors. Methods: A retrospective cohort analysis was performed using the 2004–2020 National Cancer Database including patients with a histologically confirmed malignant glomus tumor diagnosis (N = 42). Demographic factors such as race, age, sex, Hispanic status, insurance status, Charlson-Deyo score, facility type, and distance to facility were analyzed by descriptive statistics. Results: A total of 42 patients with a confirmed malignant glomus tumor diagnosis were identified in the National Cancer Database (NCDB) between 2004 – 2020. The average age of diagnosis was 60.9 years (SD = 13.7, range = 36 - 90 years). The aortic body and other paraganglia were the most common primary tumor sites (57.1%). Most patients were White (69.0%) or Black (28.6%). Most individuals (88.1%) had a Charlson-Deyo comorbidity score of 0. A higher percentage of patients were in the bottom quartile of income earners (31.4%). Fewer patients lived in metropolitan counties with populations less than 1 million compared to those that lived in counties with a population greater than 1 million (52.5%). More patients were privately insured (47.6%) relative to those who were insured by Medicare/Medicaid or uninsured. The most common treatment facility type was an academic/research program (57.5%) and patients lived an average of 40.1 miles (SD = 65.6, range = 0.6 – 265.4) from their treatment facility. Conclusions: Before this study, there had been no previous report on the socioeconomic profile of patients with malignant glomus tumors. However, our findings indicate that these patients are more prone to having a low income and that White patients are more likely to be affected. No obvious connection exists between metastases and racial minority status. Additional research is needed to grasp how socioeconomic factors, such as low income and minority status, affect the risk, diagnosis, treatment, and overall survival of individuals with malignant glomus tumors.

EPID-02. ANTIBODY REACTIVITY TO VARICELLA-ZOSTER VIRUS AND THREE OTHER HERPESVIRUSES AND SURVIVAL IN ADULTS WITH GLIOMA

Abstract Measures of Varicella-Zoster virus (VZV) have been consistently inversely associated with glioma risk, but the association with glioma survival has not been investigated. In this study we analyzed overall survival of individuals with glioma in relation to measured levels of antibodies to 4 common viral infections, measured post-diagnosis. METHODS We utilized immunoglobulin G (IgG) antibody measurements to VZV, Epstein-Barr virus (EBV), herpes simplex virus (HSV), and cytomegalovirus (CMV), collected from 1378 patients newly enrolled in the UCSF Adult Glioma Study between 1991-2010. Blood was obtained a median of 3 months post diagnostic surgery. Subject follow-up for survival is ongoing. The associations of IgG levels with overall survival were estimated using Cox models adjusted for age, sex, race, type of surgery, dexamethasone usage, and stratified by tumor grade. RESULTS The 1378 glioma patients studied had median survival of 2.1 years. VZV antibody seropositivity was associated with improved survival outcomes (Hazard ratio, HR = 0.70, 95% Confidence Interval 0.54-0.90, p = 0.0061), with a grade-IV specific association (HR=0.65, 0.48-0.87, p=0.0046). Amongst VZV seropositive cases, those in the bottom quartile of measured seroreactivity had significantly worse survival outcomes as compared to the upper three quartiles (HR = 1.31, 1.13-1.52, p = 0.0003). Antibody seropositivity to EBV was also associated with improved survival times (HR = 0.71, 0.53-0.96, p = 0.028). Antibody response to two other common viruses (CMV, HSV) were not associated with glioma survival (p = 0.213, p = 0.215, respectively). CONCLUSION This is the first study, to our knowledge, to associate virus-specific antibody levels with survival amongst glioma patients. These associations do not appear to be due to general tumor-induce immune suppression. Our results controlled for dexamethasone usage, a known immunosuppressor. IgG measurements were taken post-glioma diagnosis, therefore further study is needed to determine the direction of causation, and if anti-herpesvirus treatment, such as VZV vaccination, might be beneficial for glioma prognosis.

Establishment and Validation of a Predictive Nomogram for Postoperative Survival of Stage I Non-Small Cell Lung Cancer.

BackgroundSurgical procedure is the preferred option for people with early-stage non-small cell lung cancer (NSCLC), while nearly 30% of patients experienced metastatic or recurrent tumor after operation. The primary intention of this context is to summarize high-risk prognostic factors and set up a novel nomogram to predict the overall survival of individuals with stage I NSCLC after resection.MethodsResearch objects, 10,218 patients with stage I NSCLC after operation from 2010 to 2015, were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Independent prognostic factors, confirmed by Cox regression analyses, were integrated into a nomogram, to predict the 3-and 5-year overall survival of these individuals. The model experienced internal validation of testing cohorts above and external validation crewed by 160 patients from China. Finally, the nomogram was evaluated through several verification methods such as concordance index (C-index), calibration plots and receiver operating characteristic curve (ROC).ResultsMultivariate analysis identified that age, gender, histologic type, differentiation class, type of operation, T stage and treatment were significant predictive factors for the survival of stage I NSCLC. Based on these factors, a nomogram was constructed to predict the 3- and 5-year overall survival of these individuals. Meanwhile, in the training set, this nomogram displayed excellent superiority over the TNM staging system with abroad application, especially in C-index (0.669 vs 0.580) and the AUC (the Area Under ROC Curve) for the 3- and 5-year survival (0.678 vs 0.582; 0.650 vs 0.576). In the calibration curve, the curve representing predicted survival tended to align with the line representing actual survival as well.ConclusionA nomogram was successfully created and verified to achieve the goal that made a rounded accurate prediction on the survival of postoperative I NSCLC patients in terms of the SEER database.

Bioinformatics analysis of prognostic value and immune cell infiltration of SERPINA1 gene in cutaneous melanoma.

BackgroundCutaneous melanoma (CM) has a poor overall prognosis. Immune checkpoint inhibitor (ICI) therapy effectively improves overall survival in individuals with advanced melanoma, but only some patients benefit. Serpin Family A Member 1 (SERPINA1), a type of proteinase inhibitor that is used for many targets, is abnormally expressed and plays a vital role in multiple cancers. However, little is known about the clinical significance of SERPINA1 in CM.MethodsThe Cancer Genome Atlas (TCGA) and the gene expression omnibus (GEO) datasets were used to compare SERPINA1 expression levels. The association between SERPINA1 and other clinical factors were examined with R software, and receiver operating characteristic (ROC) curves for identification was developed. The Tumor IMmune Estimation Resource (TIMER) was used to examine the invasion of immune cells, markers for immune cells, and immunological checkpoints. The predictive value of SERPINA1 DNA methylation levels for every CpG was analyzed with the MethSurv web tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to assess the roles of genes that interacted with SERPINA1. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to predict SERPINA1’s response to ICIs.ResultsSERPINA1 was substantially expressed in CM. Overexpression of SERPINA1 was significantly associated with CM severity. The outcome for individuals with elevated SERPINA1 expression was good (HR =0.54, P<0.001). Using SERPINA1 expression levels, tumors and normal tissues could be reliably differentiated [area under the curve (AUC) =0.889]. Positive associations were found between SERPINA1 in CM and the infiltration of immune cells and immunological checkpoints [programmed cell death-1 (PD-1) and CTLA-4]. The efficacy of immune checkpoint blockade (ICB) in patients with a low expression of SERPINA1 was good. The GO pathway enrichment analysis showed that activation of neutrophil granulocytes participated in enrichment in the immune response pathway. Patients with low SERPINA1 expression had low TIDE scores.ConclusionsSERPINA1 is involved not only in the development and progression of CM but also in the immunological control of CM. Thus, SERPINA1 may serve as a possible biomarker for CM diagnosis, as well as its therapeutic target.

Current Screening Strategies for Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a dreaded malignancy with a dismal 5-year survival rate despite maximal efforts on optimizing treatment strategies. Radical surgery is the only potential curative procedure. Unfortunately, the majority of patients are diagnosed with locally advanced or metastatic disease, which renders them ineligible for curative resection. Early detection of PDAC is thus considered to be the most effective way to improve survival. In this regard, pancreatic screening has been proposed to improve results by detecting asymptomatic stages of PDAC and its precursors. There is now evidence of benefits of systematic surveillance in high-risk individuals, and the current guidelines emphasize the potential of screening to affect overall survival in individuals with genetic susceptibility syndromes or familial occurrence of PDAC. Here we aim to summarize the current knowledge about screening strategies for PDAC, including the latest epidemiological data, risk factors, associated hereditary syndromes, available screening modalities, benefits, limitations, as well as management implications.

Optimizing Therapies in Heart Failure: The Role of Potassium Binders.

Heart failure (HF) is a worrisome cardiac pandemic with a negative prognostic impact on the overall survival of individuals. International guidelines recommend up-titration of standardized therapies in order to reduce symptoms, hospitalization rates, and cardiac death. Hyperkalemia (HK) has been identified in 3–18% of HF patients from randomized controlled trials and over 25% of HF patients in the “real world” setting. Pharmacological treatments and/or cardio-renal syndrome, as well as chronic kidney disease may be responsible for HK in HF patients. These conditions can prevent the upgrade of pharmacological treatments, thus, negatively impacting on the overall prognosis of patients. Potassium binders may be the best option in patients with HK in order to reduce serum concentrations of K+ and to promote correct upgrades of therapies. In addition to the well-established use of sodium polystyrene sulfonate (SPS), two novel drugs have been recently introduced: sodium zirconium cyclosilicate (SZC) and patiromer. SZC and patiromer are gaining a central role for the treatment of chronic HK. SZC has been shown to reduce K+ levels within 48 h, with guaranteed maintenance of normokalemia for up to12 months. Patiromer has resulted in a statistically significant decrease in serum potassium for up to 52 weeks. Therefore, long-term results seemed to positively promote the implementation of these compounds in clinical practice due to their low rate side effects. The aim of this narrative review is to delineate the impact of new potassium binders in the treatment of patients with HF by providing a critical reappraisal for daily application of novel therapies for hyperkalemia in the HF setting.

The 21-Gene Recurrence Score in Clinically High-Risk Lobular and Ductal Breast Cancer: A National Cancer Database Study

ObjectiveThe aim of this study was to evaluate whether patients with invasive lobular carcinoma (ILC) are more likely to have discordant clinical and genomic risk than those with invasive ductal carcinoma (IDC) when using the 21-gene recurrence score (RS), and to assess overall survival outcomes of patients with 1–3 positive nodes and RS ≤25 with and without chemotherapy, stratified by histology.MethodsWe performed a cohort study using the National Cancer Database and included patients with hormone receptor-positive, HER2-negative, stage I–III invasive breast cancer who underwent 21-gene RS testing. Our primary outcome was rate of discordant clinical and genomic risk status by histologic subtype. Propensity score matching was used to compare 60-month overall survival in individuals with 1–3 positive nodes and RS ≤25 who did and did not receive chemotherapy.ResultsOverall, 186,867 patients were included in our analysis, including 37,685 (20.2%) patients with ILC. There was a significantly higher rate of discordant clinical and genomic risk in patients with ILC compared with IDC. Among patients with 1–3 positive nodes and RS ≤25, there was no significant difference in survival between those who did and did not receive chemotherapy in the IDC or ILC cohorts. Unadjusted exploratory analyses of patients under age 50 years with 1–3 positive nodes and RS ≤25 showed improved overall survival in IDC patients who received chemotherapy, but not among those with ILC.ConclusionOur findings highlight the importance of lobular-specific tools for stratifying clinical and genomic risk, as well as the need for histologic subtype-specific analyses in randomized trials.

NCOA4: An Immunomodulation-Related Prognostic Biomarker in Colon Adenocarcinoma and Pan-Cancer.

Treatment of cancer in humans requires a thorough understanding of the multiple pathways by which it develops. Recent studies suggest that nuclear receptor coactivator 4 (NCOA4) may be a predictive biomarker for renal cancer. In the present work, TCGA, GEPIA, and several bioinformatics approaches were used to analyze the NCOA4 expression patterns, prognostic relevance, and association between NCOA4 and clinicopathological features and immune cell infiltration. We investigated NCOA4 expression in malignancies. Low NCOA4 expression was associated with poor overall survival in individuals with malignancies such as cholangiocarcinoma, colon adenocarcinoma, and clear cell renal carcinoma. We also analyzed NCOA4 DNA methylation in normal and primary tumor tissues and investigated possible functional pathways underlying NCOA4-mediated oncogenesis. In conclusion, downregulation of NCOA4 is associated with poor prognosis, and NCOA4 may be a predictive biomarker for COAD.