Overall Survival In High-risk Patients Research Articles

Rituximab-combined anthracycline-free chemotherapy in newly diagnosed paediatric and adolescent patients with non-high-risk aggressive mature B cell lymphoma: protocol for a single-arm, open-label, multicentre, phase II study (the Japan Children’s Cancer Group Multicentre Trial, JPLSG B-NHL-20)

IntroductionChildren and adolescents with mature B cell non-Hodgkin lymphoma (B-NHL) are treated with short-intensive chemotherapy. The burden of short-term and long-term toxicity is highly relative to its high cure rate...

Factors Associated with Receipt of Adjuvant Chemotherapy in Stage II Colon Cancer.

The benefits of chemotherapy in stage II colon cancer remain unclear, but it is recommended for high-risk stage II disease. Which patients receive chemotherapy and its impact on survival remains undetermined. The National Cancer Database was surveyed between 2004 and 2016 for stage II colon cancer patients. Patients were categorized as high- or average-risk as defined by the National Comprehensive Cancer Network. The demographic characteristics of high- and average-risk patients who did and did not receive chemotherapy were compared using univariate and multivariable analyses. The survival of high- and average-risk patients was compared based on receipt of chemotherapy with Cox hazard ratios and Kaplan-Meier curves. Overall, 84,424 patients met the inclusion criteria. A total of 34,868 patients were high-risk and 49,556 were average-risk. In high-risk patients, the risk factors for not receiving chemotherapy included increasing age, distance from the treatment facility, Charlson-Deyo score, and lack of insurance. In average-risk patients, factors associated with receipt of chemotherapy were decreasing age, distance from the treatment facility, Charlson-Deyo score, and non-academic association of the treatment facility. In both, chemotherapy was significantly associated with increased survival on the Kaplan-Meier curve. In the Cox hazard ratio, only high-risk patients benefited from chemotherapy (hazard ratio 1.183, confidence interval 1.116-1.254). Factors associated with not receiving chemotherapy in high-risk stage II colon cancers included increasing age, medical comorbidities, increasing distance from the treatment facility, and lack of insurance. Chemotherapy is associated with improved overall survival in high-risk patients.

MP11-12 DEVELOPMENT OF A RISK MODEL FOR TIME TO SECOND PROGRESSION IN PATIENTS WITH HIGH-RISK METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER TREATED WITH ABIRATERONE ACETATE AND ANDROGEN DEPRIVATION THERAPY

You have accessJournal of UrologyCME1 Apr 2023MP11-12 DEVELOPMENT OF A RISK MODEL FOR TIME TO SECOND PROGRESSION IN PATIENTS WITH HIGH-RISK METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER TREATED WITH ABIRATERONE ACETATE AND ANDROGEN DEPRIVATION THERAPY Shintaro Narita, Takafumi Yanagisawa, Shingo Hatakeyama, Kenichi Hata, Hiromi Sato, Ryuichiro Sagehashi, Yuya Sekine, Mizuki Kobayashi, Taketoshi Nara, Kazuyuki Numakura, Mitsuru Saito, Chikara Ohyama, Takahiro Kimura, and Tomonori Habuchi Shintaro NaritaShintaro Narita More articles by this author , Takafumi YanagisawaTakafumi Yanagisawa More articles by this author , Shingo HatakeyamaShingo Hatakeyama More articles by this author , Kenichi HataKenichi Hata More articles by this author , Hiromi SatoHiromi Sato More articles by this author , Ryuichiro SagehashiRyuichiro Sagehashi More articles by this author , Yuya SekineYuya Sekine More articles by this author , Mizuki KobayashiMizuki Kobayashi More articles by this author , Taketoshi NaraTaketoshi Nara More articles by this author , Kazuyuki NumakuraKazuyuki Numakura More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Chikara OhyamaChikara Ohyama More articles by this author , Takahiro KimuraTakahiro Kimura More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003226.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Evidence on risk stratification in patients treated with doublet therapy with abiraterone acetate is limited. In this study, we developed a risk stratification model in patients with de novo high-risk mCSPC who received abiraterone acetate plus androgen deprivation therapy based on clinical risk factors. METHODS: Medical records of 224 high-risk patients with de novo mCSPC treated with abiraterone acetate plus androgen deprivation therapy at 11 centers between 2015 and 2022 were retrospectively reviewed. Castration-resistant prostate cancer (CRPC)-free, progression-free survival 2 (PFS2), and overall survival (OS) were estimated using the Kaplan–Meier method. The association of pretreatment clinical risk factors with PFS2 was evaluated by Cox proportional hazard models and survival outcomes were classified according to the number of risk factors. RESULTS: Median PFS2 was 43 months; second-progression occurred in 76 (34.2%) patients. On multivariable analysis, the following four risk factors were identified as independent predictors of PFS2: primary Gleason pattern 5 (HR 1.97, 95% CI 1.20–3.22), presence of liver metastasis (HR 2.05, 95% CI 1.02–4.13), extent of disease score ≥3 (HR 2.25, 95% CI 1.16–4.34), and abnormal hemoglobin (HR 1.73, 95% CI 1.02–2.92). Significant differences in PFS2 were observed among the three risk groups (low vs. intermediate; p=0.006, intermediate vs. high; p<0.001). Median PFS2 and OS of high-risk patients were significantly worse in the low- and intermediate-risk groups. The median PFS2 of low-risk patients with no or one factor was not reached, whereas that of intermediate-risk patients with two or three factors and high-risk patients with four factors were 42 months and 16 months, respectively. Median OS was 24 months in high-risk patients, whereas it was not reached in low- and intermediate-risk patients. CONCLUSIONS: We successfully classified patients with high-risk mCSPC treated with abiraterone acetate based on four clinical risk factors. Risk-adapted treatment may be beneficial for selected patients with mCSPC in this triplet therapy era. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e128 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shintaro Narita More articles by this author Takafumi Yanagisawa More articles by this author Shingo Hatakeyama More articles by this author Kenichi Hata More articles by this author Hiromi Sato More articles by this author Ryuichiro Sagehashi More articles by this author Yuya Sekine More articles by this author Mizuki Kobayashi More articles by this author Taketoshi Nara More articles by this author Kazuyuki Numakura More articles by this author Mitsuru Saito More articles by this author Chikara Ohyama More articles by this author Takahiro Kimura More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement PDF downloadLoading ...

Prognostic and immunological role of sulfatide-related lncRNAs in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Long non-coding RNAs (lncRNAs) play important roles in the occurrence and development of HCC through multiple pathways. Our previous study reported the specific molecular mechanism for sulfatide regulation of integrin αV expression and cell adhesion in HCC cells through lncRNA AY927503. Next, it is necessary to identify more sulfatide-related lncRNAs, explore their clinical signifcance, and determine new targeted treatment strategies. Microarrays were used to screen a complete set of lncRNAs with different expression profiles in sulfatide-treated cells. Sulfatide-related lncRNAs expression data and corresponding HCC patient survival information were obtained from the The Cancer Genome Atlas (TCGA) database, and the prognosis prediction model was constructed based on Cox regression analysis. Methylated RNA immunoprecipitation with next generation sequencing (MeRIP-seq) was used to detemine the effect of sulfatide on lncRNAs m6A modification. Tumor Immune Estimation Resource (TIMER) and Gene set nnrichment analysis (GSEA) were utilized to enrich the immune and functional pathways of sulfatide-related lncRNAs. A total of 85 differentially expressed lncRNAs (|Fold Change (FC)|>2, P<0.05) were screened in sulfatide-treated HCC cells. As a result, 24 sulfatide-related lncRNAs were highly expressed in HCC tissues, six of which were associated with poor prognosis in HCC patients. Based on thses data, a sulfatide-related lncRNAs prognosis assessment model for HCC was constructed. According to this risk score analysis, the overall survival (OS) curve showed that the OS of high-risk patients was significantly lower than that of low-risk patients (P<0.05). Notably, the expression difference in sulfatide-related lncRNA NRSN2-AS1 may be related to sulfatide-induced RNA m6A methylation. In addition, the expression level of NRSN2-AS1 was significantly positively correlated with immune cell infiltration in HCC and participated in the peroxisome and Peroxisome proliferator-activated receptor (PPAR) signaling pathways. In conclusion, sulfatide-related lncRNAs might be promising prognostic and therapeutic targets for HCC.

Prognostic Assessment and Risk Stratification in Patients With Postoperative Major Salivary Acinar Cell Carcinoma.

To investigate the clinicopathological features and prognosis of postoperative major salivary acinar cell carcinoma (MSACC) and develop a prognostic model. Retrospective cohort analysis of a public database. Patients with MSACC were identified from the Surveillance, Epidemiology, and End Results database (1975-2019). Overall survival (OS) was evaluated using Kaplan-Meier curves and a log-rank test. Univariate and multivariate Cox analyses were performed to explore independent prognostic factors. The prognostic model was constructed using screened variables and further visualized with a nomogram and web calculator, and assessed by concordance index, the area under the curve, calibration curve, and decision-making curve analysis. An upward trend in the incidence of MSACC was observed throughout the study period. A total of 1398 patients were enrolled (training cohort: 978; validation cohort: 420), and the 5- and 10-year OS rates were 97.7% and 81.6%, respectively. Age, marital status, sex, histological grade, T stage, and lymph node status were identified as prognostic factors for OS. A novel nomogram was developed and showed excellent discrimination and clinical applicability. Additionally, a web calculator was designed to dynamically predict patient survival. Based on the nomogram-based score, a risk stratification system was constructed to distinguish patients with different risks. The OS of high-risk patients was significantly lower than that of the low-risk subgroup. Long-term survival in postoperative MSACC was influenced by 6 prognostic factors. The proposed model enables individualized survival prediction and risk stratification, prompting us to be vigilant in high-risk subgroups and consider timely adjustment of subsequent treatment.

Integrated profiling uncovers prognostic, immunological, and pharmacogenomic features of ferroptosis in triple-negative breast cancer.

Ferroptosis is an iron-dependent type of regulated cell death triggered by the toxic buildup of lipid peroxides on cell membranes. Nonetheless, the implication of ferroptosis in triple-negative breast cancer (TNBC), which is the most aggressive subtype of breast carcinoma, remains unexplored. Three TNBC cohorts-TCGA-TNBC, GSE58812, and METABRIC-were adopted. Consensus molecular subtyping on prognostic ferroptosis-related genes was implemented across TNBC. Ferroptosis classification-relevant genes were selected through weighted co-expression network analysis (WGCNA), and a ferroptosis-relevant scoring system was proposed through the LASSO approach. Prognostic and immunological traits, transcriptional and post-transcriptional modulation, therapeutic response, and prediction of potential small-molecule agents were conducted. Three disparate ferroptosis patterns were identified across TNBC, with prognostic and immunological traits in each pattern. The ferroptosis-relevant scoring system was proposed, with poorer overall survival in high-risk patients. This risk score was strongly linked to transcriptional and post-transcriptional mechanisms. The high-risk group had a higher response to anti-PD-1 blockade or sunitinib, and the low-risk group had higher sensitivity to cisplatin. High relationships of risk score with immunological features were observed across pan-cancer. Two Cancer Therapeutics Response Portal (CTRP)-derived agents (SNX-2112 and brefeldin A) and PRISM-derived agents (MEK162, PD-0325901, PD-318088, Ro-4987655, and SAR131675) were predicted, which were intended for high-risk patients. Altogether, our findings unveil prognostic, immunological, and pharmacogenomic features of ferroptosis in TNBC, highlighting the potential clinical utility of ferroptosis in TNBC therapy.

Outcomes of Allogeneic Stem Cell Transplant for Multiple Myeloma

Background Allogeneic stem cell transplant (allo-SCT) for treatment of multiple myeloma (MM) is controversial. For some, allo-SCT may drive treatment-resistant disease into remission through a graft vs myeloma effect. For others, it incurs considerable morbidity from opportunistic infections and graft vs host effects. Allo-SCT usage for MM has increased over the past 25 years despite mixed efficacy and the absence of clear treatment guidelines. We aimed to determine the natural history of patients who underwent an allo-SCT following an autologous stem cell transplant (ASCT) and identify characteristics associated with outcome. Methods We retrospectively analyzed 89 patients diagnosed with multiple myeloma who had received an allo-SCT following an ASCT between 2000 and 2022 at Mayo Clinic Rochester. Patient data were obtained from the Mayo Clinic Transplant Center Database and our institution's electronic medical records. Overall survival (OS) and progression free survival (PFS) were calculated as time from allo-SCT to death from any cause and first observation of relapse or death, respectively. OS and PFS rates were estimated using the Kaplan-Meier method. P < 0.05 was considered statistically significant. Results The cohort is characterized as follows: median patient age of 51.3 years, 71% male, 90% white/Caucasian. Indication for allo-SCT were 91.0% (N=81) relapsed/progressive disease, 9.0% (N=8) high risk in remission. Cytogenetic risk stratification at diagnosis was available for 94% of patients (N=84) with 63% (N=56) standard risk, 32% (N=28) high risk according to International Myeloma Working Group criteria. By conditioning regimen, 55% (N=49) underwent full myeloablative allo, 45% (N=40) non-myeloablative (mini)-allo. Median follow-up, OS, and PFS was 11.5, 1.7, and 0.8 years, respectively (Table 1). OS was 46% (N=41) at 2 years, 26% (N=21) at 4 years, and 16% (N=14) at 8 years (Figure 1). Outcome was not significantly impacted by age, sex, race, indication for allo-SCT, or myeloablative regimen. Patient cytogenetic risk at diagnosis approached, but did not reach, statistical significance (p=0.22) with overall survival of high-risk patients being 32% (N=9), 18% (N=5), and 7.1% (N=2) at 2, 4, and 8 years, respectively, compared to 52% (N=29), 27% (N=15), and 20% (N=11) over the same times in standard risk. PFS was 27% (N=24) at 2 years follow-up, 16% (N=14) at 4 years, and 7.9% (N=7) at 8 years (Figure 1). This did not vary significantly by age, race, indication for allo-SCT, cytogenetic risk, or conditioning regimen. Sex approached, but did not reach, statistical significance (p=0.16) with progression-free survival of females being 19% (N=5), 15% (N=4), and 7.7% (N=1) at 2, 4, and 8 years follow-up, respectively, compared to males at 30% (N=19), 16% (N=10), and 9.5% (N=6) over the same times. Discussion Long-term survival was achieved in less than 20% of patients who underwent allo-SCT following an ASCT. Nearly 75% of patients experienced disease progression or death by 2 years. This suggests minimal benefit to the use of allo-SCT as treatment for multiple myeloma outside of select patients. Novel therapeutics such as chimeric antigen receptor T cells (CAR-T) or bispecific T-cell engager (BiTE) should be considered as an alternative. Subsequent studies will further examine patient characteristics and associated outcomes to determine the population best suited for allo-SCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Development of a prognostic prediction model based on a combined multi-omics analysis of head and neck squamous cell carcinoma cell pyroptosis-related genes.

This study aimed to understand the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) and to develop and validate a prognostic model for HNSCC based on pyroptosis-associated genes (PAGs) in nasopharyngeal carcinoma. The Cancer Genome Atlas database was used to identify differentially expressed PAGs. These genes were analyzed using the Kyoto Encyclopedia of Genes and Genomes functional annotation analyses and Gene Ontology analyses. The NLR family pyrin domain containing 1 (NLRP1) gene, charged multivesicular body protein 7 (CHMP7) gene, and cytochrome C (CYCS) gene were used to create a prognostic model for HNSCC. The results of the Kaplan-Meier (K-M) and Cox regression analyses indicated that the developed model served as an independent risk factor for HNSCC. According to the K-M analysis, the overall survival of high-risk patients was lower than that of low-risk patients. The hazard ratios corresponding to the risk scores determined using the multivariate and univariate Cox regression analyses were 1.646 (95% confidence interval (CI): 1.189–2.278) and 1.724 (95% CI: 1.294–2.298), respectively, and the area under the receiver operator characteristic curve was 0.621. The potential mechanisms associated with the functions of the identified genes were then identified, and the tumor microenvironment and levels of immune cell infiltration achieved were analyzed. The immune infiltration analysis revealed differences in the distribution of Th cells, tumor-infiltrating lymphocytes, regulatory T cells, follicular helper T cells, adipose-derived cells, interdigitating dendritic cells, CD8+ T cells, and B cells. However, validating bioinformatics analyses through biological experiments is still recommended. This study developed a prognostic model for HNSCC that included NLRP1, CHMP7, and CYCS.

Effect of more versus less frequent abdominopelvic computed tomography follow-up testing on overall survival in patients with stage II or III colon cancer.

3604 Background: Patients with colon cancer undergo an abdominopelvic computed tomography (AP-CT) scan surveillance every 6-12 months for five years after surgery. However, evidence of survival benefit from more intensive AP-CT patients in stage II and III colon cancer is still elusive. Methods: A total of 2,137 patients with stage II-III colon cancer who received curative aim surgery were analyzed in the Yonsei Cancer Registry Database between Jan 1, 2005, to Dec 31, 2015. The surveillance start date was defined as 90 days after curative resection or one day after adjuvant chemotherapy. All patients had at least one AP-CT for two years after the surveillance period. The average interval of AP-CT per patient was calculated as the postoperative surveillance duration divided by the number of AP-CT examinations. Patients who underwent AP-CT with an average interval of 6 months and 12 months were assigned to the high-frequent and low-frequent surveillance groups. Association of AP-CT frequency and demographic factors with overall survival (OS) were evaluated. Univariate and multivariate analyses were conducted. Results: Among 2,137 patients who underwent curative aim surgery, the median intervals of AP-CT scan were 6.1 months in high-frequent surveillance and 10.8 months in the less-frequent surveillance group, respectively. The 5-year overall survival (OS) was not significantly different in both groups; however, OS was significantly longer in the high-frequent surveillance group of patients who harvested lymph nodes less than 12 in curative resection ( P = 0.015) or measured postoperative serum carcinoembryonic antigen (CEA) level higher than 5 ng/ml ( P = 0.023). Of note, high-frequent surveillance group detected liver metastasis earlier (6.7 months) than the low-frequent group, leading to more curative aim metastasectomy (28.0% vs 4.3%, P = 0.020), and significantly longer 5-year OS (62.2% vs 34.8%, P = 0.017). Multivariate analysis showed that harvesting lymph nodes less than 12 (HR = 4.37, P = 0.004) and postoperative CEA level higher than 5 ng/ml (HR = 7.39, P &lt; 0.001) were prognostic factors for overall survival. Conclusions: The average interval of AP-CT in patients with stage II-III colon cancer is not associated with improved OS. However, a high-frequent AP-CT enabled early detection of liver metastases, leading to the improved OS in high-risk patients, including the number of harvested lymph nodes less than 12 or postoperative CEA level is higher than 5 ng/ml. The risk-stratified approach is warranted to guide postoperative colon cancer surveillance.

Establishment of a Prognostic Model of Lung Adenocarcinoma Based on Tumor Heterogeneity.

Lung cancer is one of the main cancer types due to its persistently high incidence and mortality, yet a simple and effective prognostic model is still lacking. This study aimed to identify independent prognostic genes related to the heterogeneity of lung adenocarcinoma (LUAD), generate a prognostic risk score model, and construct a nomogram in combination with other pathological characteristics to predict patients’ overall survival (OS). A significant amount of data pertaining to single-cell RNA sequencing (scRNA-seq), RNA sequencing (RNA-seq), and somatic mutation were used for data mining. After statistical analyses, a risk scoring model was established based on eight independent prognostic genes, and the OS of high-risk patients was significantly lower than that of low-risk patients. Interestingly, high-risk patients were more sensitive and effective to immune checkpoint blocking therapy. In addition, it was noteworthy that CCL20 not only affected prognosis and differentiation of LUAD but also led to poor histologic grade of tumor cells. Ultimately, combining risk score, clinicopathological information, and CCL20 mutation status, a nomogram with good predictive performance and high accuracy was established. In short, our research established a prognostic model that could be used to guide clinical practice based on the constantly updated big multi-omics data. Finally, this analysis revealed that CCL20 may become a potential therapeutic target for LUAD.

A Signature of N6-methyladenosine Regulator-Related Genes Predicts Prognoses and Immune Responses for Head and Neck Squamous Cell Carcinoma.

This study aimed to construct a signature of N6-methyladenosine (m6A) regulator-related genes that could be used for the prognosis of head and neck squamous cell carcinoma (HNSCC) and to clarify the molecular and immune characteristics and benefits of immune checkpoint inhibitor (ICI) therapy using the prognostic signature to define the subgroups of HNSCC. This study showed that eighteen m6A regulators were abnormally expressed in the Cancer Genome Atlas (TCGA) HNSCC tissues compared with those in normal tissues. We constructed a signature of 12 m6A regulator-related genes using the Cox risk model, combined with the least absolute shrinkage and selection operator (Lasso) variable screening algorithm. Based on the median of the signature risk score, the patients were divided into high- and low-risk groups. The Kaplan–Meier survival analyses showed that patients with high-risk scores demonstrated poorer overall survival (OS) than those with low-risk scores based on TCGA-HNSCC data (p <0.001). The OS of high-risk patients was significantly worse than that of low-risk patients in the GSE65858 (p <0.001) and International Cancer Genome Consortium (ICGC) oral cancer cohorts (p = 0.0089). Furthermore, immune infiltration analyses showed that 8 types of immune cell infiltration showed highly significant differences between the two risk groups (p <0.001). In the Imvigor210CoreBiologies dataset of patients who received ICIs, the objective response rate (ORR) of the low-risk group (32%) was significantly higher than that of the high-risk group (13%). Additionally, patients in the high-risk group presented with a more significant adverse OS than that of the low-risk group (p = 0.00032). GSE78220 also showed that the ORR of the low-risk group (64%) was higher than that of the high-risk group (43%) and the OS of low-risk patients was better than that of high-risk patients (p = 0.0064). The constructed prognostic signature, based on m6A regulator-related genes, could be used to effectively distinguish between prognoses for HNSCC patients. The prognostic signature was found to be related to the immune cell infiltration of HNSCC; it might help predict the responses and prognoses of ICIs during treatment.

Atorvastan, Apsirin and Hydorxyurea for an Effective and Low-Cost Treatment in High-Risk Polycythemia Vera

Introduction: Polycythemia vera (PV) treatment focuses on preventing thrombotic events and delaying transformation to myelofibrosis or leukaemia. According to risk stratification, low-risk patients require therapeutic phlebotomy combined with acetylsalicylic acid, whilst the treatment of high-risk patients with PV relies on cytoreductive therapies, employing hydroxyurea (HU), ruxolitinib, or interferons. However, in low- and middle-income countries, the availability and cost of these drugs poses a challenge in treating high-risk patients, so optimising existing resources is required. Method: A prospective longitudinal study aimed to investigate the combination of atorvastatin (ATV), aspirin, and low-dose HU as a therapeutic strategy to treat PV in high-risk patients. The study evaluated the effect of statins on erythroid colony proliferation in vitro, as well as the applicability of ATV (20 mg/day), acetylsalicylic acid (100 mg/day), and hydroxiurea (500 mg/day) in high-risk patients with PV from La Paz, Bolivia, residing at 3,600 metres above sea level. Results: Simvastatin (3.5 μm) inhibited UKE-1 cell (JAK2V617F mutated) proliferation at 33%, and burstforming unit-erythroid colonies from patients with PV at 61%. Patients receiving ATV, aspirin, and low-dose HU displayed a good response and adequate tolerance to treatment (13-years follow-up). No patients experienced myelofibrosis or transformation to leukaemia, and no severe adverse events were observed. Conclusions: This accessible, effective, and low-cost therapeutic strategy could improve adherence to treatment and the overall survival of high-risk patients with PV in resource-limited countries.

Transcriptome-based identification of molecular markers related to the development and prognosis of Colon cancer

Colon cancer is one of the most common malignant tumors of the digestive system that seriously threaten human health and whose pathogenesis has not been completely elucidated. The purpose of this study was to investigate genes related to colon cancer and explore their potential values in colon cancer prognosis. Clinical information and transcriptome data of patients with colon cancer were obtained from UCSC Xena. The differentially expressed genes (DEGs) between colon cancer tissues and normal colon tissues were identified and analyzed by R packages. A total of 1414 DEGs were identified, including 593 upregulated and 821 downregulated genes in colon cancer tissues. These DEGs were enriched in multiple biological processes, such as cell junction organization, mitotic nuclear division and digestive tract development. The expression of 14 DEGs (such as PBK, C2CD4A and CXCL10) was correlated with tumor stages of colon cancer. Kaplan-Meier survival analysis showed that the expression of 139 DEGs (such as HSPA1A, CCDC136 and SEZ6L2) was related to the prognosis of patients with colon cancer. The prognosis prediction model constructed based on 35 DEGs could effectively estimate 3- and 5-year overall survival (OS) of patients with colon cancer (AUC of 3- and 5-year OS were 0.816 and 0.897, respectively). In addition, the OS of high-risk patients was significantly poorer than that of low-risk patients. In conclusion, the present study identified multiple genes related to the development and prognosis of colon cancer, which would provide novel molecular targets for the diagnosis and therapy of colon cancer.

Prognostic Role and Potential Mechanisms of the Ferroptosis-Related Metabolic Gene Signature in Hepatocellular Carcinoma.

PurposeFerroptosis, as a novel regulated cell death form, has a close interaction with metabolism, which is largely unknown in cancer. In the present study, we conducted a comprehensive analysis of ferroptosis-related metabolic genes to delineate the metabolic signatures induced by ferroptosis and evaluate its prognostic significance in hepatocellular carcinoma (HCC).MethodsThe ferroptosis-related metabolic genes (Fer-MRGs) were identified by correlation analyses with transcriptome data from The Cancer Genome Atlas and Gene Expression Omnibus. Then, univariate and the least absolute shrinkage and selection operator Cox regression analysis was used to establish a novel risk score model. Univariate and multivariate COX analyses were used to identify independent prognostic factors for overall survival (OS) of HCC, and a nomogram was developed. The Fer-MRGs’ expression was further evaluated by quantitative real-time polymerase chain reaction in HCC.ResultsA total of 77 metabolic genes were identified as Fer-MRGs, and 26 were found with prognostic values for OS of HCC. Then, a novel nine-gene (AKR1C3, ATIC, G6PD, GMPS, GNPDA1, IMPDH1, PRIM1, RRM2, and TXNRD1) risk score model was constructed. Survival analyses showed worse OS in high-risk patients both in the training and validation groups. The model was also identified as an independent prognostic factor for HCC, and a prognostic nomogram for OS was further established with superior discriminative capacity and prediction accuracy. Notably, close correlations were also identified between the risk score and the expression of immune checkpoint genes, immune subtypes of tumor, and susceptibility of HCC to chemotherapeutic agents. Finally, elevated expression of eight Fer-MRGs (except for IMPDH1) was further verified in 16 pairs of HCC tumor and adjacent tissues.ConclusionThese results indicated the intense interaction between ferroptosis and metabolism, the significant role of ferroptosis-related MRGs, and the great potential of the novel risk score model for prognosis prediction in HCC.

Predicting reintervention after thoracic endovascular aortic repair of Stanford type B aortic dissection using machine learning.

To construct models for predicting reintervention after thoracic endovascular aortic repair (TEVAR) of Stanford type B aortic dissection (TBAD). A total of 192 TBAD patients who underwent TEVAR were included; 68 (35.4%) had indications for reintervention. Clinical characteristics, aorta characteristics on pre- and postoperative computed tomography angiography, and aorta characteristics on immediate postoperative aortic digital subtraction angiography were collected. The least absolute shrinkage and selection operator (LASSO) regression was applied to identify the risk factors for reintervention. Eight classifiers were used for modeling. The models were trained on 100 train-validation random splits with a ratio of 2:1. The performance was evaluated by the receiver operating characteristic curve. Seven predictors of reintervention were identified, including maximum false lumen diameter, aortic diameter measured at the level of approximately 15 mm distal to the left subclavian artery, aortic diameter measured at the level of the diaphragm, false lumen diameter measured at the level of the celiac artery, number of bare-metal and covered stents, number of bare-metal stents, and residual perfusion of the false lumen. Logistic regression (LR) yielded the highest performance, with an area under the curve of 0.802. A nomogram built for clinical use showed good calibration. The cutoff value for dividing patients into low- and high-risk subgroups was 0.413. Kaplan-Meier curves showed that the overall survival of high-risk patients was significantly shorter than that of low-risk patients (both p < 0.05). Our nomogram could predict the reintervention after TEVAR in patients with TBAD, which may facilitate patient selection and surveillance strategies. • Seven risk factors of reintervention after TEVAR of TBAD were identified for modeling. • Logistic regression performed best in predicting reintervention with an AUC of 0.802. • Patients with a high risk of reintervention had shorter OS than those with a low risk.

Multi-gene prognostic assays and age-related differences in prediction of pathologic complete response to neoadjuvant chemotherapy and survival in breast cancer.

591 Background: Multi-gene testing of primary breast tumors in early-stage breast cancer is used to classify the risk of developing distant metastases and predict the benefit of adjuvant chemotherapy. The association between the tumor genomic prognostic score (GPS) and response to neoadjuvant chemotherapy (NACT) and survival is not well characterized. Our objective was to describe the association between GPS and rates of pathologic complete response (PCR) and subsequent overall survival among women with or without PCR. Methods: We utilized the National Cancer Database to perform a hospital-based, retrospective cohort study of breast cancer patients ages 18 years and older. We included women diagnosed with first primary stages I-III hormone receptor positive (HR+), HER2 negative (HER2-) breast cancer who received NACT and surgery between 2010 and 2017. Women were categorized as having low (0-10 or 200), intermediate (11-25 or 300), or high-risk (25-199 or 400) GPS based on OncotypeDX or MammaPrint scores. Multivariable modified Poisson regression models with robust error variance were used to estimate the crude and adjusted relative risk and 95% confidence intervals (CI) for PCR associated with GPS groups. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) and 95% CI for associations between the GPS and overall survival (OS) in women who did and did not have PCR. Results: A cohort of 3,446 women (mean [SD] age, 56.7 [12.0] years; median [interquartile range] follow-up of 47 [31-68] months) who received genomic testing and neoadjuvant chemotherapy were included in our analysis, of which 935 (27%) were low risk, 1,357 (39%) intermediate risk, and 1,154 (34%) high risk GPS. The relative risk of PCR for all women with high GPS was 1.81 (95% CI, 1.47-2.22; p &lt; 0.001) in crude models and 1.49 (95% CI, 1.16-1.92; p = 0.002) after full adjustment compared to low GPS. Across all models, having a high GPS was significantly associated with achieving PCR in younger women ( &lt; 65 years). In women ages ≥65 years, the association between GPS and PCR was not predictive nor statistically significantly. Among women with no response or partial response to NACT, high GPS was associated with a significantly increased risk of overall mortality (HR 2.41; 95% CI, 1.61-3.60; p &lt; 0.001) compared to low GPS. Conversely, in women who did achieve PCR, GPS was not predictive of overall mortality across all age groups. Conclusions: In women with HR+/HER2- breast cancer, high risk GPS was predictive of PCR following NACT, primarily in younger women ( &lt; 65 years). Our findings also indicated GPS was associated with lower OS in high-risk patients who do not achieve PCR and unpredictive of OS in those without PCR. The utility of tumor genomic testing in the neoadjuvant setting needs further investigation.

The prognostic value of an autophagy-related lncRNA signature in hepatocellular carcinoma

BackgroundlncRNA may be involved in the occurrence, metastasis, and chemical reaction of hepatocellular carcinoma (HCC) through various pathways associated with autophagy. Therefore, it is urgent to reveal more autophagy-related lncRNAs, explore these lncRNAs’ clinical significance, and find new targeted treatment strategies.MethodsThe corresponding data of HCC patients and autophagy genes were obtained from the TCGA database, and the human autophagy database respectively. Based on the co-expression and Cox regression analysis to construct prognostic prediction signature.ResultsFinally, a signature containing seven autophagy-related lncRNAs (PRRT3-AS1, RP11-479G22.8, RP11-73M18.8, LINC01138, CTD-2510F5.4, CTC-297N7.9, RP11-324I22.4) was constructed. Based on the risk score of signature, Overall survival (OS) curves show that the OS of high-risk patients is significantly lower than that of low-risk patients (P = 2.292e−10), and the prognostic prediction accuracy of risk score (AUC = 0.786) is significantly higher than that of ALBI (0.532), child_pugh (0.573), AFP (0.5751), and AJCC_stage (0.631). Moreover, multivariate Cox analysis and Nomogram of risk score are indicated that the 1-year and 3-year survival rates of patients are obviously accuracy by the combined analysis of the risk score, child_pugh, age, M_stage, and Grade (The AUC of 1- and 3-years are 0.87, and 0.855). Remarkably, the 7 autophagy-related lncRNAs may participate in Spliceosome, Cell cycle, RNA transport, DNA replication, and mRNA surveillance pathway and be related to the biological process of RNA splicing and mRNA splicing.ConclusionIn conclusion, the 7 autophagy-related lncRNAs might be promising prognostic and therapeutic targets for HCC.

Laparoscopic transhiatal esophagectomy in esophageal cancer patients with high-risk post-operative complications.

Surgical treatment of esophageal cancer is challenging, due to considerable morbidity, especially in high surgical risk patients. While transhiatal esophagectomy leads to good oncological outcomes and reduced postoperative complications, less invasive techniques might further improve outcomes. Our goal was to compare results of laparoscopic transhiatal esophagectomy (LTE) with open transhiatal esophagectomy (OTE) in esophageal cancer patients at high surgical risk. From 2014 to 2020, 128 patients were identified. Seventy received OTE while 51 received LTE. After propensity score matching (1:1), postoperative complications, analysis of overall and disease-free survival, and survival-related prognostic factors were assessed in two groups of 48 patients. Ninety-one (77%) patients were men with a mean age of 65 ± 10.3 years. Those who underwent OTE experienced more clinical and surgical complications. In LTE patients, the number of mean resected lymph nodes was 25.9, and in patients who had OTE, it was 17.4 (P < 0.001). Overall survival was 56.0% in the LTE group and 33.6% (P = 0.023) in the OTE group. In multivariable analysis of overall survival, open surgery and incomplete pathological response were seen as worse negative factors. In multivariable analysis, metastatic lymph nodes, incomplete pathologic response, surgical complications, and a Charlson's index > 2 (P = 0.014) were associated with poor prognosis. Both surgical methods are safe with similar morbidity and mortality; however, LTE was associated with fewer complications, a higher number of resected lymph nodes, better overall survival, and more prognostic factors related to global and disease-free overall survival in high-risk patients.

Clinical characteristics and prognostic significance of extramedullary involvement in childhood acute myeloid leukemia

Background. Extramedullary infiltration (EI) is relatively common in children with acute myeloid leukemia (AML) (up to 20-25 %). However, its clinical and prognostic significance remains poorly understood.Objective: to describe clinical features and to define prognostic significance of EI in children with AML.Materials and methods. The subjects of retrospective observational study were 228 children with de novo AML. The median age was 6.6 years. All of them were treated according to the protocol AML-MM-2006 from April 2007 to June 2018.All patients with EI were divided into three cohorts according to the localization of the lesions: 1) central nervous system (CNS) involvement (CNS group), 2) other localizations apart from CNS (myelosarcomas (MS) group), 3) combined lesions (CNS + MS group).Results. EI was diagnosed in 84 patients (36.84 %) with de novo AML. Among them 47 (55.95 %) had CNS involvement, 20 (23.81 %) had MS, 15 (17.86 %) had both CNS involvement and MS. 5-year overall survival (OS) rate was slightly higher in patients with CNS involvement than in children without EI - 80 ± 12 % vs 71 ± 9 %, p = 0.26, however OS in patients with MS was significantly lower - 45 ± 16 % vs 71 ± 9 %, p &lt;0.001. In addition, OS in high-risk patients according to the protocol AML-MM-2006 who underwent allogenic hematopoietic stem cell transplantation (HSCT) without EI and with MS (± CNS involvement) was similar to OS in main groups - 81 ± 11 % and 42 ± 26 % respectively, p = 0.004. 5-year event-free survival in patients with MS was also lower than in children without EI - 38 ± 16 % vs 51 ± 8 %, p = 0.011.Conclusion. Patients with MS had worse 5-year OS and EFS than children without EI according to our study. Moreover allogenic HSCT conducted in first clinical remission did not improve the survival rate. Neuroleukemia as the only EI was not an unfavorable prognostic factor in our cohort of AML patients and was more often associated with inv(16).

M6A RNA methylation regulators were associated with the malignancy and prognosis of ovarian cancer

ABSTRACT N6-methyladenosine (m6A) RNA methylation regulators play a regulatory role in tumor pathogenesis and development. However, the role of m6A regulator genes in ovarian cancer (OC) has not been fully elucidated. This study aims to investigate the mRNA expressions, clinicopathological features, and prognostic values of m6A regulators in OC. Here, we demonstrate that the 17 m6A RNA methylation regulators are differentially expressed in ovarian cancer and normal tissues. By using consensus clustering, all ovarian cancer patients can be divided into two subgroups (cluster 1 and 2) based on the expression of 17 m6A RNA methylation regulators. Using Gene Set Enrichment Analysis, we identified that cluster 1 was most connected to oxidative phosphorylation pathways. Regression models identified that prognosis is associated with HNRNPA2B1, KIAA1429, and WTAP. qRT-PCR result show that the expression trends of HNRNPA2B1 and KIAA1429 are consistent with the predicted results. Multivariate Cox regression analysis results show that the risk score was an independent predictive factor in OV. The overall survival of high-risk patients was significantly shorter than that of low-risk patients. ROC curve analysis showed that the prognostic signature precisely predicted the 5-year survival of OV patients. A nomogram was developed to predict each patient’s survival probability and well calibrated and showed a satisfactory discrimination. Dendritic fraction, macrophage fraction, and neutrophil fraction showed higher fraction in high-risk patients. In conclusion, m6A RNA methylation regulators are vital participants in ovarian cancer pathology, and three-gene mRNA levels are valuable factors for prognosis predictions.