Indicator Of Overall Survival Research Articles

Analysis of relapse-free and overall survival in oncoplastic and organ-preserving surgeries in patients with breast cancer

Purpose of the study. To study the results of relapse-free and overall survival during organ- preserving and oncoplastic surgeries in patients with breast cancer.Materials and methods. A prospective clinical study of 84 patients was carried out in the mammology department on the basis of GBUZ NSO "GKB № 1". The first group of patients (40 patients) underwent OPR with ALAE - oncoplastic resection of the mammary gland with axillary lymphadenectomy. The second group (44 patients) WSR with ALAE - wide sector resection of the mammary gland with axillary lymphadenectomy.During the study, the patients were comparable in age, stage (TNM), histological type, and morphogenetic data. The survival rate was studied by the number of local relapses and distant metastases, using laboratory and instrumental studies. The quality of life was assessed on the basis of anamnestic data (Karnofsky index, ECOG scale).Results. In the first group of patients, disease-free and overall survival rate was 97.5 %. At the same time, a local recurrence was found in a patient with a triple negative tumor type, distant metastases to the lungs in a patient with a HER2/neu-positive type. In the second group, relapse-free survival was 95.4 %, overall - 97.7 %. Relapses in two patients with HER2/neu-positive type, metastases to the lungs in a patient with triple negative type.Conclusion. Relapse-free survival rates are 2.1 % higher in group I patients who underwent oncoplastic resection with axillary lymphadenectomy. And the indicators of overall survival in patients of both groups do not differ relatively.

The Systematic Landscape of Nectin Family and Nectin-Like Molecules: Functions and Prognostic Value in Low Grade Glioma.

Objective: Nectin and nectin-like molecules (Necls) are molecules that are involved in cell–cell adhesion and other vital cellular processes. This study aimed to determine the expression and prognostic value of nectin and Necls in low grade glioma (LGG). Materials and Methods: Differentially expressed nectin and Necls in LGG samples and the relationship of nectin family and Necls expression with prognosis, clinicopathological parameters, and survival were explored using The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and Repository of Molecular Brain Neoplasia Data (REMBRANDT) databases. Univariate and multivariate Cox analysis models were performed to construct the prognosis-related gene signature. Kaplan-Meier curves and time-dependent receiver operating characteristic (ROC) curves and multivariate Cox regression analysis, were utilized to evaluate the prognostic capacity of the four-gene signature. Gene ontology (GO)enrichment analysis and Gene Set Enrichment Analyses (GSEA) were performed to further understand the underlying molecular mechanisms. The Tumor Immune Estimation Resource (TIMER) was used to explore the relationship between the four-gene signature and tumor immune infiltration. Results: Several nectin and Necls were differentially expressed in LGG. Kaplan–Meier survival analyses and Univariate Cox regression showed patients with high expression of NECTIN2 and PVR and low expression of CADM2 and NECTIN1 had worse prognosis among TCGA, CGGA, and REMBRANDT database. Then, a novel four-gene signature was built for LGG prognosis prediction. ROC curves, KM survival analyses, and multivariate COX regression indicated the new signature was an independent prognostic indicator for overall survival. Finally, GSEA and GO enrichment analyses revealed that immune-related pathways participate in the molecular mechanisms. The risk score had a strong negative correlation with tumor purity and data of TIMER showed different immune cell proportions (macrophage and myeloid dendritic cell) between high- and low-risk groups. Additionally, signature scores were positively related to multiple immune-related biomarkers (IL 2, IL8 and IFNγ). Conclusion: Our results offer an extensive analysis of nectin and Necls levels and a four-gene model for prognostic prediction in LGG, providing insights for further investigation of CADM2, NECTIN1/2, and PVR as potential clinical and immune targets in LGG.

CircCHST15 is a novel prognostic biomarker that promotes clear cell renal cell carcinoma cell proliferation and metastasis through the miR-125a-5p/EIF4EBP1 axis

BackgroundCircular RNAs (circRNAs) have been indicated as potentially critical mediators in various types of tumor progression, generally acting as microRNA (miRNA) sponges to regulate downstream gene expression. However, the aberrant expression profile and dysfunction of circRNAs in human clear cell renal cell carcinoma (ccRCC) need to be further investigated. This study mined key prognostic circRNAs and elucidates the potential role and molecular mechanism of circRNAs in regulating the proliferation and metastasis of ccRCC.MethodscircCHST15 (hsa_circ_0020303) was identified by mining two circRNA microarrays from the Gene Expression Omnibus database and comparing matched tumor versus adjacent normal epithelial tissue pairs or matched primary versus metastatic tumor tissue pairs. These results were validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. We demonstrated the biological effect of circCHST15 in ccRCC both in vitro and in vivo. To test the interaction between circCHST15 and miRNAs, we conducted a number of experiments, including RNA pull down assay, dual-luciferase reporter assay and fluorescence in situ hybridization.ResultsThe expression of circCHST15 was higher in ccRCC tissues compared to healthy adjacent kidney tissue and higher in RCC cell lines compared to normal kidney cell lines. The level of circCHST15 was positively correlated with aggressive clinicopathological characteristics, and circCHST15 served as an independent prognostic indicator for overall survival and progression-free survival in patients with ccRCC after surgical resection. Our in vivo and in vitro data indicate that circCHST15 promotes the proliferation, migration, and invasion of ccRCC cells. Mechanistically, we found that circCHST15 directly interacts with miR-125a-5p and acts as a microRNA sponge to regulate EIF4EBP1 expression.ConclusionsWe found that sponging of miR-125a-5p to promote EIF4EBP1 expression is the underlying mechanism of hsa_circ_0020303-induced ccRCC progression. This prompts further investigation of circCHST15 as a potential prognostic biomarker and therapeutic target for ccRCC.

182P Comprehensive assessment of the immunophenotype of peripheral blood lymphocytes, inflammatory factors, the immunophenotype of lymphocytes infiltrating the tumor and clinical indicators for overall survival and progression-free survival in patients with gastric cancer

182P Comprehensive assessment of the immunophenotype of peripheral blood lymphocytes, inflammatory factors, the immunophenotype of lymphocytes infiltrating the tumor and clinical indicators for overall survival and progression-free survival in patients with gastric cancer

Three-year outcomes of sandwich therapy in patients with locally advanced cancer of the middle and lower rectum

Background. The most important criteria for the effectiveness of the treatment of locally advanced rectal cancer are indicators of overall survival (OS) and disease-free survival (DSF). Conducting systemic chemotherapy in addition to chemoradiotherapy at the preoperative stage can increase these indicators.Objective: to study analyze the indicators of 3-year OS and DFS, as well as the frequency of local relapses and distant metastases.Materials and methods. From 2013 to 2020, 72 patients with T≥3(CRM+)N0–2M0 lower and middle ampullar rectal cancer were included in the study using sandwich therapy. At the first stage, 2 courses of induction polychemotherapy were carried out according to the CapOx scheme (capecitabine 2000 mg/m2 orally for 14 days and oxaliplatin 130 mg/m2 intravenously once every 3 weeks). Further, chemoradiation therapy was carried out with a total focal dose of 50–56 Gy while taking capecitabine 1650 mg/m2 per day orally on the days of irradiation. After the end of chemotherapy, the patients underwent 2 courses of consolidating polychemotherapy according to the CapOx scheme (capecitabine 2000 mg/m2 orally for 14 days and oxaliplatin 130 mg/m2 intravenously once every 3 weeks). The control group consisted of 72 patients who underwent neoadjuvant treatment in accordance with current clinical guidelines (chemotherapy course with a total focal dose of 50–56 Gy while taking capecitabine 1650 mg/m2 per day orally on the days of irradiation).Results. In 19 (26.4 %) patients from the study group and in 6 (8.3 %) patients from the control group, the achievement of pCR was recorded (p = 0.006). The overall complication rate was 48 (66.7 %) in the study group and 37 (51.4 %) in the control group (p = 0.072), the frequency of grade III–IV toxicity was 8 (11.1 %) and 7 (9.7 %), respectively (p = 0.072). Sphincter-sparing surgical interventions were performed in 52 (72.2 %) and 40 (55.6 %) patients in the sandwich-therapy group and the control group of chemoradiation therapy, respectively (p = 0.037). Resection in the R0 volume was achieved in 71 (98.6 %) and 72 (100 %) patients, respectively (p = 0.316).Conclusion. The use of sandwich therapy is a promising trend in the treatment of patients with locally advanced rectal cancer. There were no significant differences in the frequency of 3-year OS (96.1 % versus 91.5 %, p = 0.247), DFS (89.8 % versus 84.0 %, p = 0.117) and local relapses (0 % versus 4.2 %, p = 0.997). In our study, statistically significant differences were obtained in the incidence of distant metastases (6.9 % versus 18.1 %, p = 0.05), which may indicate a positive trend towards an increase in OS and DFS rates.

A Novel Lipid Prognostic Signature of ADCY2, LIPE, and OLR1 in Head and Neck Squamous Cell Carcinoma.

Simple SummaryClinically, aberrant lipid metabolism is responsible for overweight and/or obesity. Overweight is considered as an independent factor of cancer risk in 2019. Therefore, lipid metabolic reprogramming is an emerging hallmark of malignancy. It is an urgent need to comprehensively understand the relationship among lipid metabolism and HNSCC and identify a valuable biomarker for predicting prognosis of HNSCC patients. Three new findings were found in this study. Firstly, we identified the lipid-related differentially expressed genes (DEGs) by using the GEO microarrays and TCGA dataset. A novel lipid-related mRNA prognostic signature (LRPS, consisting of ADCY2, LIPE and OLR1) was developed, which could predict the survival and prognosis of HNSCC patients as an independent effective prognostic factor. Secondly, we found that the LRPS could indicate the type of infiltrated immune cells in HNSCC tumor microenvironment. Thirdly, we verified that the LPPS score could interpret the TP53 status of HNSCC. Our new findings indicated that LRPS has a potential to be a promising indicator of overall survival, TP53 status, and immune characteristics in HNSCC, and perhaps can monitor and guide the treatment efficacy and prognosis of HNSCC in the future.BackgroundHead and neck squamous cell carcinoma (HNSCC) is characterized by a high frequency of lymph node metastasis and a high mortality. Lipid metabolic reprogramming is an emerging carcinogen as its role in fulfilling cancer growth and spread. However, little is known about the correlation between lipid metabolism and HNSCC.Materials and MethodsExpressions of lipid-related genes were obtained from the Cancer Genome Atlas (TCGA) and Gene expression Omnibus (GEO) databases for differential and functional analyses. A total number of 498 patients from TCGA with complete information were included to identify a lipid-related prognostic signature (LRPS), based on ADCY2, LIPE, and OLR1, by using univariate and multivariate Cox regression analyses. LRPS-high and LRPS-low groups were accordingly divided to pathway and cell enrichment analyses.ResultsLRS-low patients had a better overall survival and relapse - free survival than LRS-high ones in HNSCC. The LRPS-high group was significantly related to perineural invasion of cancer, cancer-related pathways, high TP53 mutation rate, high proportion of natural killer T cells (NKT), dendritic cells, monocytes, Treg, and M1 and M2 macrophage infiltration in HNSCC tumor tissues. Conversely, the LRPS-low group correlated with DNA damage-related and T-cell-regulated pathways, low frequency of mutated TP53, and high infiltration of B cells and CD4+ effector cells including Th1 and Th2.ConclusionLRPS has a potential to be a promising indicator of overall survival, prognosis, TP53 status, and immune characteristics in HNSCC.

Long non-coding RNA profile study identifies an immune-related lncRNA prognostic signature for prostate adenocarcinoma

Prostate adenocarcinoma (PRAD) is the highest incidence rate of male urogenital morbidity worldwide. Long non-coding RNAs (lncRNAs), as a significant class of gene expression regulators, play a critical role in immune regulation. The purpose of this study is to explore a new immune related lncRNA signature to exactly predict the prognosis of PRAD patients. In this study, we conducted a genome-wide comparative analysis of lncRNA expression profiles in 532 patients with PRAD from the Cancer Genome Atlas (TCGA) database. The immune-related lncRNAs were identified by Cox regression model, and then a new five immune-related lncRNAs signature (FRMD6-AS2, AC008770.3, AC109460.3, AC011899.2, and AC008063.1) were constructed, which could predict the prognosis of PRAD patients. Univariate and multivariate Cox regression analysis showed that the signature could be an independent prognostic indicator of overall survival (OS). Through further study of different clinic-pathological parameters, we found that PRAD samples can be divided into high-risk groups with shorter OS and low-risk groups with longer OS by the signature. Principal component analysis showed that five immune-related lncRNA signature could distinguish the high-risk group from low-risk group in view of the immune-related lncRNAs. The difference of immune status between the two groups was observed by gene set enrichment analysis and the ESTIMATE algorithm. Except FRMD6-AS2, the expression of the other 4 lncRNAs were remarkably up-regulated in tumor tissues. In conclusion, the identified five immune-related lncRNAs signature had important clinical significance in prognosis prediction, and can be used as potential immunotherapy targets for PRAD patients.

Head and Neck Cancer Patients Under (Chemo-) Radiotherapy Undergoing NUTritional Intervention: Results From the Prospective Randomized HEADNUT-Trial

<h3>Purpose/Objective(s)</h3> Patients with squamous cell carcinoma of the head and neck (HNSCC) under (chemo-)radiotherapy are at high risk of malnutrition. There are no studies investigating the influence of nutritional status on an altered side effect spectrum and only very few studies examining bioelectric impedance analysis (BIA) and its impact as a prognostic indicator in patients with HNSCC undergoing (chemo-)radiotherapy. Our prospective, randomized, and controlled HEADNUT-trial presented here aimed at preventing increasing malnutrition under radiotherapy or concurrent chemoradiotherapy through specialized and individualized nutritional counseling. Additionally, we investigated whether parameters from BIA were suitable indicators for (threatening) malnutrition and inspected their prognostic effect on (clinical) outcome. <h3>Materials/Methods</h3> Between October 2018 and October 2020, 61 patients were randomized into an intervention and control group. Questionnaires (MUST, NRS-2002, and Nutriscore), clinical examinations, laboratory analyses, and BIA were used to assess nutritional status for all patients at the beginning and end of therapy as well as every 2 weeks during therapy. The intervention consisted of an individualized nutritional counseling every 2 weeks during therapy. <h3>Results</h3> Median baseline BMI for all participants was 23.8 (14.5-37.2) kg/m² and dropped to 22.9 (16.8-33) kg/m² after therapy (<i>P</i> < 0.001). In all patients, median baseline fat-free mass index (FFMI) was 18.1 (14-24.7) kg/m² and decreased to 17.8 (13.4-21.6) kg/m² till the end of therapy (<i>P</i> < 0.001). Compliant patients with a BMI < 22 kg/m² presented with less weight loss in the intervention group compared to the control (<i>P</i> = 0.015, CI: 0.33-2.95). At baseline, MUST was the only screening-test which showed both good sensitivity (86%) and specificity (88%) in detecting malnutrition. Median follow-up was 15 (1-26) months. 2-year overall survival rate was 70% in the control and 79% in the intervention group (log-rank <i>P</i> = 0.79). Pretherapeutic phase angle, posttherapeutic FFMI and albumin level were prognostic indicators for overall survival (log-rank <i>P</i> = 0.002, <i>P</i> = 0.008 and <i>P</i> = 0.016). <h3>Conclusion</h3> Malnutrition negatively impacts patients' outcome under (chemo-)radiotherapy. Baseline phase angle, posttherapeutic FFMI and albumin level are proposed as reliable indicators for overall survival.

Renin-angiotensin system inhibitors can be a first choice drug for hypertension in patients treated with vascular endothelial growth factor inhibitors

Abstract Background Vascular endothelial growth factor Signaling Pathway (VSP) inhibitor suppresses tumor growth in solid cancers with disorganized tumor vasculature.1 However, VSP inhibitor often provokes hypertension as an adverse effect.2 The VSP inhibitor-induced hypertension may lead to a dose reduction or discontinuation of the treatment, which cause to poor prognosis. Therefore, it is important to investigate the appropriate anti-hypertensive treatment during cancer therapy. Although renin-angiotensin system (RAS) inhibitor or calcium channel blocker (CCB) is recommended to first-line anti-hypertensive drugs for cancer patients,3 it has not been well-elucidated whether RAS inhibitor or CCB is a beneficial impact for clinical outcome. Purpose The aim of this study is to clarify whether RAS inhibitor or CCB would be an effective drug as the first antihypertensive drug during VSP inhibitor therapy. Method From the LIFE Study database which consisted of 14 municipality-level information from claims data between 2016 and 2020, 1,263 cancer patients treated with VSP inhibitors were retrospectively reviewed. All patients were stratified into two groups according to hypertensive drugs: (1) RAS inhibitors alone (n=512) and (2) CCBs alone (n=751) (Figure 1). The time to treatment failure (TTF) was substituted as an alternative clinical indicator of overall survival. The Kaplan-Meier survival method with the log-rank test was conducted to compare the TTF between the two groups. In addition, Cox proportional hazard model adjusted with baseline clinical characteristics was performed to analyze determinant factors for TTF. Results There were no difference in baseline characteristics including age, sex, primary cancer site, the type of VSP inhibitors, and past medical histories between the two groups, excepted for renal failure. The rate of renal failure was significantly higher in the RAS inhibitor group than in the CCB group (p=0.013). TTF in the patients treated with RAS inhibitors were significantly longer than that with CCB (median TTF [25th–75th percentile]: 183 [61–455] vs. 153 [61–351] days, p=0.020) (Figure 2). In Cox proportional hazard analysis adjusted with age, sex, past medical history, primary cancer lesion, and type of VSP inhibitors, RAS inhibitor was a significantly independent favorable factor to TTF, compared to CCB (Hazard ratio 0.86, 95% confidence interval [0.77–0.97], p=0.011). Conclusion RAS inhibitor is associated with a favorable clinical outcome than CCB, and can be a first choice for treating hypertension during cancer therapy with VSP inhibitors. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI) Figure 1. Patient screening and enrollmentFigure 2. Antihypertensive drugs &amp; TTF

Impact of hypertension on clinical outcome in patients treated with vascular endothelial growth factor inhibitors

Abstract Background Vascular endothelial growth factor (VEGF) family is overexpressed in the tumor microenvironment and induces tumor angiogenesis.1 VEGF signaling pathway (VSP) inhibitors are essential therapeutic drugs for solid cancer patients.2 However, VSP inhibitors often provoke drug-specific anti-angiogenesis in normal tissues, which was referred to as on-target toxicity.2 Hypertension (HTN) is one of the most frequent adverse events caused by VSP inhibitors. A previous report demonstrated that VSP inhibitor-induced hypertension is a favorable prognostic factor, contrarily.3However, multiple VSP inhibitors are administered in various cancer types, and then the relation between VSP inhibitor-associated hypertension and clinical outcome is still controversial. Purpose The aim of this study is to elucidate the impacts of HTN and the timing of onset on clinical outcome during cancer therapy with VSP inhibitors. Method We reviewed 2,348 patients who were treated with VSP inhibitors from the LIFE Study database, consisting of 14 municipality-level information from claims data between 2016 and 2020. According to the timing of HTN onset mode, the patients were stratified into 3 groups; (1) new-onset HTN group (n=334): de novo development after VSP inhibitor administration, (2) pre-existing HTN group (n=1,363): existing HTN at baseline, including aggravation after VSP inhibitor initiation, and (3) no HTN group (n=651) (Figure 1). The time to treatment failure (TTF) was applied as a surrogate clinical indicator of overall survival. Event-free survival analysis with the log-rank test was conducted for time to first treatment failure amongst the 3 groups. In addition, Cox proportional hazard models adjusted with clinical characteristics were performed to investigate independent factors for TTF. Results In the event-free survival analysis, both the new-onset HTN and the pre-existing HTN were associated with prolongation of TTF, compared to the non-HTN (p&amp;lt;0.001 and p&amp;lt;0.001, respectively, by Bonferroni correction) (Figure 2). The New-onset HTN was significantly associated with longer TTF than pre-existing HTN (p&amp;lt;0.001). In Cox proportional hazard model adjusted with age, sex, past medical history, primary cancer lesion, and type of VSP inhibitors, the new-onset HTN and the pre-existing HTN were independent favorable factors, compared to the non-HTN [new-onset HTN: Hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.54 - 0.71, p&amp;lt;0.001; and pre-existing HTN: HR 0.85, 95% CI 0.77 - 0.94, p&amp;lt;0.005]. Moreover, the New-onset HTN was also a significant factor for longer TTF, compared to the pre-existing HTN [HR 0.72, 95% CI 0.64 - 0.82, p&amp;lt;0.001]. Conclusion In patients treated with VSP inhibitors, both new-onset and pre-existing HTN are independent factors for a favorable clinical outcome, especially new-onset HTN after VSP inhibitors administration. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI) Figure 1. Patient screening and enrollmentFigure 2. HTN &amp; TTF

Urothelial cancer: population-based analysis of the problem in Ukraine

The aim of this work was to conduct a population analysis on the basis of the National Cancer Registry with the primary goal: to determine the effectiveness of urothelial cancer treatment in Ukraine; and the secondary goal: to identify the main trends and approaches to therapy with an assessment of their impact on overall survival. Materials and methods. The design of the study was retrospective observational. The analysis was conducted based on the data of the National Cancer Registry from 2008 to 2020. A total of 12,698 patients with urothelial tumors of the upper urinary tract and bladder who underwent surgical treatment were analyzed. Statistical sampling was performed based on the creation of the most homogeneous groups of patients with bladder cancer (BC) and the upper urinary tract carcinoma (UUTc) who had the required number of notified parameters for further analysis. The primary objectives of the analysis were to determine: the average age of primary detection of the studied nosologies, level of detection depending on gender, frequency of diagnosis verification before surgery, extent of surgery, frequency of postoperative complications based on data on 30-day rehospitalization, the level of deviation of the principles for prophylactic medical patients’ examination from generally accepted recommendations. The secondary objective was to assess the cumulative survival of patients with urothelial tumors depending on the localization of the primary tumor and the type of surgery (organ-sparing or radical). Results. Organ-sparing treatment was more typical for BC, while radical treatment was performed in 15 % of patients with carcinomas. Organ-sparing treatment was more typical for UUTc (40%). It should be noted that in this nosology it is acceptable for invasive forms of urothelial cancer. The level of 30-day hospitalization was low in both pathologies, with a slightly greater advantage of UUTc. The level of complications is grade III according to the Clavien-Dindo classification, averaging 0.2 % for the entire pool of patients. For BC, the overall survival rates by stages were: I — 73%, II — 49 %, III — 18 % and IV — 11 % (chi-square=1,807.207; p= 0.000001). For UUTc, the levels of 5-year overall survival correspond to the literature data, but there is a significant negative tendency to decrease the latter after a 10-year period for all stages (chi-square = 146.298; p = 0.000003). In Ukraine, organ-sparing treatment for UUTc was not inferior to radical nephroureterectomy in the context of 5-year survival (51.3 vs. 51%; log-rank test). The obtained data testify in favor of the 15% advantage of the total survival of patients who underwent radical nephroureterectomy at the premises of the National Cancer Institute (high volume center), compared to other regions of Ukraine. Levels of 5- and 10-year survival in both nosologies were characterized by a statistically non-significant advantage of UUTc over BC of 7 %. Conclusions. Superficial and locally advanced tumors are the most complex ones in the treatment of urothelial cancer of the bladder and upper urinary tract in Ukraine. Superficial tumors require the most radical surgeries and subsequent effective local treatment. Locally advanced tumors require a comprehensive approach to treatment, adequate systemic therapy influences the final indicators of overall survival. In cases of surgical resectability and preservation of renal function, UUTc requires organ-sparing treatment; this approach aims to increase creatinine clearance in patients before systemic chemotherapy and to reduce the likelihood of progression of comorbidities and associated mortality.

Effect of Tumor Microenvironment and Angiogenesis on Clinical Outcomes of Primary Central Nervous System Lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare lymphoma, and the disease course is often aggressive with poor prognosis outcomes. PCNSL undergoes germinal center reactions and impairs B-cell maturation. However, angiogenesis is also involved in the tumorigenesis and progression of PCNSL. This study investigated the effects of the tumor microenvironment and angiogenesis-associated genomic alterations on the outcomes of PCNSL. The analysis also evaluated the influence of treatment modality and timing on PCNSL survival using partial least squares variance-based path modeling (PLS-PM). PLS-PM can be used to evaluate the complex relationship between prognostic variables and disease outcomes with a small sample of measurements and structural models. A total of 19 immunocompetent PCNSL samples were analyzed by exome sequencing. Our results suggest that the timing of radiotherapy and mutations of ROBO1 and KAT2B are potential indicators of PCNSL outcomes and may be affected by baseline characteristics such as age and sex. Our results also showed that patients with no mutations of ROBO1 and KAT2B, SubRT subgroup showed favorable survival outcomes compared with no SubRT subgroup in short-term follow-up. All SubRT patients have received high-dose methotrexate induction chemotherapy in the initial treatment. Therefore, initial induction chemotherapy combined with subsequent radiotherapy might improve survival outcomes in PCNSL patients who have no ROBO1 and KAT2B somatic mutations in short-term follow-up. The overall findings suggest that the tumor microenvironment and angiogenesis-associated genomic alterations and treatment modalities are potential indicators of overall survival and may be affected by the baseline characteristics of PCNSL patients.

Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma: A single-arm, multicenter, prospective study

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.

Predicting the Survival and Immune Landscape of Colorectal Cancer Patients Using an Immune-Related lncRNA Pair Model.

BackgroundAccumulating evidence has demonstrated that immune-related long non-coding ribonucleic acids (irlncRNAs) can be used as prognostic indicators of overall survival (OS) in patients with colorectal cancer (CRC). Our aim in this research, therefore, was to construct a risk model using irlncRNA pairs with no requirement for a specific expression level, in hope of reliably predicting the prognosis and immune landscape of CRC patients.MethodsClinical and transcriptome profiling data of CRC patients downloaded from the Cancer Genome Atlas (TCGA) database were analyzed to identify differentially expressed (DE) irlncRNAs. The irlncRNA pairs significantly correlated with the prognosis of patients were screened out by univariable Cox regression analysis and a prognostic model was constructed by Lasso and multivariate Cox regression analyses. A receiver operating characteristic (ROC) curve was then plotted, with the area under the curve calculated to confirm the reliability of the model. Based on the optimal cutoff value, CRC patients in the high- or low-risk groups were distinguished, laying the ground for evaluating the risk model from the following perspectives: survival, clinicopathological traits, tumor-infiltrating immune cells (TIICs), antitumor drug efficacy, kinase inhibitor efficacy, and molecules related to immune checkpoints.ResultsA prognostic model consisting of 15 irlncRNA pairs was constructed, which was found to have a high correlation with patient prognosis in a cohort from the TCGA (p < 0.001, HR = 1.089, 95% CI [1.067–1.112]). According to both univariate and multivariate Cox analyses, this model could be used as an independent prognostic indicator in the TCGA cohort (p < 0.001). Effective differentiation between high- and low-risk patients was also accomplished, on the basis of aggressive clinicopathological characteristics, sensitivity to antitumor drugs, and kinase inhibitors, the tumor immune infiltration status, and the expression levels of specific molecules related to immune checkpoints.ConclusionThe prognostic model established with irlncRNA pairs is a promising indicator for prognosis prediction in CRC patients.

917P Head and neck cancer patients under (chemo-)radiotherapy undergoing nutritional intervention: Results from the prospective randomized HEADNUT-trial

Patients with head and neck squamous cell carcinoma (HNSCC) are often malnourished before starting the primary or adjuvant radiotherapy (RT) or chemoradiotherapy (CRT). Due to therapy related adversary effects of the RT or CRT the number of malnourished patients rises to 88% during ongoing therapy. Malnutrition can have a negative influence on therapycourse and clinical outcome. There are still not enough prospective, randomized studies on the influence of nutritional status on adversary effects of (C-)RT during therapy. From October 2018 to October 2020, the nutritional status of 61 patients with HSNCC, randomized into a control and intervention group (IG), was measured at the beginning, every 2 weeks during and at the end of therapy. The risk of malnutrition was evaluated with established malnutrition screening tools (NRS-2002, MUST, Nutriscore) and 3-day diet diaries, patients underwent clinical examinations, laboratory analyses and bioelectrical impedance analyses. In addition, the IG had individualized nutritional counseling every 2 weeks. Before therapy, the median BMI of all patients was 23.8 (14.5-37.2) kg/m2 and after therapy median BMI fell to 22.9 (16.8-33) kg/m2 (p<0.001). The baseline median fat-free mass index (FFMI) for all patients was 18.1 (14-24.7) kg/m2, which dropped to 17.8 (13.4-21.6) kg/m2 at the ending of therapy (p<0.001). Control group patients lost more weight compared to compliant intervention group participants with a BMI <22 kg/m2(p=0.0015, CI: 0.33-2.95). MUST was the only questionnaire, which showed high sensitivity (86%) and specificity (88%) at baseline in predicting malnutrition. The 2-year overall survival rate was 70% in the control group 79% in the intervention group (log-rank p=0.79). A clear impact on the overall survival rate was observed in pretherapeutic phase angle, posttherapeutic FFMI and albumin level in blood as indicators (log-rank p=0.002, p=0.008, p=0.016). Malnutrition has an adverse impact on patients’ outcome undergoing (chemo-) radiotherapy. Pretherapeutic phase angle, posttherapeutic FFMI and albumin level can be considered as indicators for overall survival.

Prognostic performance of different lymph node classification systems in young gastric cancer.

Accurate staging plays a pivotal role in cancer care. The lymph node (LN) ratio (LNR) and the log odds of positive LNs (LODDS) have been suggested as alternatives to the N staging since the TNM system has the risk of stage migration. The prognostic significance of LNR and LODDS in young patients with gastric cancer (GC) has not been reported. This study aims to investigate the correlations between LNR and LODDS and survival of young patients with GC, and compare the predictive performance of these LN staging methods. GC patients before the age of 40 from 2004 to 2016 in the Surveillance, Epidemiology and End Results database were enrolled. The prognostic evaluation of the N factor, LNR and LODDS was compared using the time-dependent receiver operating characteristic (ROC) analysis, area under the curve (AUC), C-index and Akaike information criterion (AIC). Multivariate survival analysis identified that the LNR and LODDS were significantly independent prognostic indicators for overall survival (OS) in young patients with GC and in the subgroups comprised of patients with ≤15 LNs examined. The time-dependent ROC curves of the LNR and LODDS were continuously superior to that of the N factor in predicting OS during the observation period. And the AUCs revealed that the predictive accuracy of the LNR and LODDS was remarkably superior to the N factor at 1 and 3 years (P<0.05). The model incorporating LNR or LODDS had higher C-index and lower AIC when comparing to the model incorporating the N factor. The LNR and LODDS improve accuracy of survival risk prediction in young patients with GC when comparing to the N factor. These two novel LN classification methods should be considered as alternatives to the N staging for the prognostic prediction of young patients with GC.

Development and validation of nomograms for predicting survival and recurrence in patients with parotid gland cancer.

To develop nomograms for predicting recurrence risk and long-term survival in patients with parotid gland cancer (PGC). A total of 301 consecutive patients with PGC who underwent surgery were enrolled and randomly divided into a training cohort (n=210) and a validation cohort (n=91). Predictive nomograms were constructed based on the independent indicators of overall survival (OS) and disease-free survival (DFS) as determined by multivariate Cox regression analysis. The discrimination and calibration of nomograms were evaluated using C-indices and calibration curves. Six independent predictors of OS were identified. Incorporating these factors, the nomogram showed good concordance statistics of 0.84 and 0.78 in predicting the 5-year OS in the training and validation cohorts. Five independent predictors of DFS were identified and integrated into the nomogram. The concordance statistics were 0.84 and 0.74 in predicting the 5-year DFS in the training and validation cohorts. The predictive performance of the nomograms outperformed the TNM model. Additionally, the patients were divided into two groups according to the nomogram score, and significant differences in OS and DFS were observed between the high risk and low risk groups. Finally, the role of postoperative treatments was evaluated based on the risk stratification; patients at high risk of disease recurrence showed an improvement in DFS after receiving postoperative treatments. The nomogram showed good performance in predicting both OS and DFS in patients with PGC. It might be useful for selecting patients for postoperative treatments.

Plasma extracellular vesicle microRNA-491-5p as diagnostic and prognostic marker for head and neck squamous cell carcinoma.

Poor survival of patients with locally advanced head and neck squamous cell carcinoma (LA‐HNSCC) is partly due to early diagnosis difficulties and the lack of reliable biomarkers for predicting treatment outcomes. In the discovery cohort, plasma‐derived extracellular vesicles (EVs) from LA‐HNSCC patients (n = 48) and healthy volunteers (n = 12) were used for profiling for microRNA (miRNA) expression by NanoString analysis. Ten EV‐associated miRNAs were differentially expressed between LA‐HNSCC patients and healthy volunteers. Subsequently, the results were validated in the individual discovery and additional cases (HNSCC, n = 73; control, n = 20) by quantitative RT‐PCR. Among 10 EV‐miRNAs, four (miR‐27b‐3p, miR‐491‐5p, miR‐1910‐5p, and miR‐630) were significantly dysregulated in LA‐HNSCC patients (n = 73) compared with healthy volunteers (n = 20). The miRNA prediction models were developed to discriminate HNSCC patients from healthy volunteers. The model using miR‐491‐5p was selected as a diagnostic biomarker for LA‐HNSCC with a sensitivity and specificity of 46.6% and 100%, respectively (P < .001). The dynamic changes of miRNA model score (ΔmiRNAs) were determined using scores pre‐ and postdefinitive treatment to further investigate the prognostic value of miRNA prediction models. The univariate and multivariate analyses indicated that ΔmiR‐491‐5p was the most powerful and independent prognostic indicator for overall survival (hazard ratio [HR] 5.66, 95% confidence interval, 1.77‐18.01; P = .003) and disease‐free survival (HR 2.82, 95% CI, 1.13‐7.05; P = .027) of HNSCC patients. In summary, the miR‐491‐5p prediction model could serve as a blood‐based diagnostic marker for LA‐HNSCC. Moreover, ΔmiR‐491‐5p could be a potential monitoring prognostic marker to reflect the survival of HNSCC patients.

Prognostic value of preoperative circulating tumor cells counts in patients with UICC stage I-IV colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. There is an urgent need to identify prognostic markers for patients undergoing curative resection of CRC. The detection of circulating tumor cells in peripheral blood is a promising approach to identify high-risk patients with disseminated disease in colorectal cancer. This study aims to evaluate the prognostic relevance of preoperative CTCs using the Cellsearch® system (CS) in patients, who underwent resection with curative intent of different stages (UICC I-IV) of colorectal cancer. Out of 91 Patients who underwent colorectal resection, 68 patients were included in this study. CTC analysis was performed in patients with CRC UICC stages I-IV immediately before surgery. Data were correlated with clinicopathological parameters and patient outcomes. One or more CTCs/7.5 mL were detected in 45.6% (31/68) of patients. CTCs were detected in all stages of the Union of International Cancer Control (UICC), in stage I (1/4, 25%), in stage II (4/12, 33.3%), in stage III (5/19, 26.3%) and in stage IV (21/33, 63.6%). The detection of ≥ 1 CTCs/ 7.5ml correlated to the presence of distant overt metastases (p = 0.014) as well as with shorter progression-free (p = 0.008) and overall survival (p = 0.008). Multivariate analyses showed that the detection of ≥ 1 CTCs/ 7.5ml is an independent prognostic indicator for overall survival (HR, 3.14; 95% CI, 1.18-8.32; p = 0.021). The detection of CTCs is an independent and strong prognostic factor in CRC, which might improve the identification of high-risk patients in future clinical trials.

P62 Overexpression Promotes Bone Metastasis of Lung Adenocarcinoma out of LC3-Dependent Autophagy.

p62 protein has been implicated in bone metastasis and is a multifunctional adaptor protein usually correlated with autophagy. Herein, we investigated p62 expression and its prognostic significance in bone metastasis of lung adenocarcinoma, and analyzed whether the mechanism involved depends on autophagy. mRNA and protein expression of p62, LC3B and Beclin 1 were detected by reverse transcription-quantitative PCR and western blotting, respectively, in fresh bone metastasis tissues (n=6 cases) and normal cancellous bone tissues (n=3 cases). The association between p62 and LC3B expression and patient prognosis was subsequently analyzed in 62 paraffin-embedded bone metastasis specimens by immunohistochemistry assay. Small interfering RNA (siRNA) was employed to downregulate p62 expression in SPC-A-1 and A549 cells. Cell proliferation and migration ability were tested by CCK8, CCF and Transwell assays respectively. Autophagy was induced by Rapamycin or inhibited by Atg 7 knockout/Chloroquine in A549 cells and p62 and LC3II/I expression were analyzed. After subcutaneous inoculation or intracardial injection of A549 cells into nude mice, the effect of p62 downregulation in vivo was analyzed by histopathological examination. The results showed that p62, LC3B and Beclin 1 mRNA and protein were all overexpressed in bone metastasis tissues (all P<0.01). Patient samples with high p62 expression levels were significantly associated with more bone lesions (>3), shorter overall survival rates and shorter progression free survival rates compared with patients having lower p62 expression (P=0.014, P=0.003, P=0.048, respectively). Cox regression analysis identified p62 expression as an independent prognostic indicator of overall survival of patients with bone metastasis (P=0.007). In vitro p62 downregulation inhibited SPC-A-1 and A549 cells migration but had no effect on cell proliferation. After autophagy induction or inhibition, p62 expression involved in autophagy flux and changed inconsistently according to the switch of LC3I to LC3II in different autophagy conditions. In vivo p62 downregulation had no effect on growth of subcutaneous tumor. Lung or bone metastasis lesion was not found in all mice model. These findings suggested that p62 overexpression promotes tumor cell invasion out of LC3-dependent autophagy, which could be used a potential prognostic biomarker and therapeutic target for bone metastasis of lung adenocarcinoma.