scholarly journals Risk-Adapted Postmastectomy Radiotherapy Decision Based on Prognostic Nomogram for pT1-2N1M0 Breast Cancer: A Multicenter Study

2020 ◽  
Vol 10 ◽  
Author(s):  
Ming Li ◽  
Jinbo Yue ◽  
Xiangbo Wan ◽  
Bin Hua ◽  
Qiuan Yang ◽  
...  

PurposeThe aim of this study was to develop a widely accepted prognostic nomogram and establish a risk-adapted PMRT strategy based on locoregional recurrence for pT1-2N1M0 breast cancer.Methods and MaterialsA total of 3,033 patients with pT1-2N1M0 breast cancer treated at 6 participating institutions between 2000 and 2016 were retrospectively reviewed. A nomogram was developed to predicted locoregional recurrence-free survival (LRFS). A propensity score-matched (PSM) analyses was performed in risk-adapted model.ResultsWith the median follow-up of 65.0 months, the 5-year overall survival (OS), disease free survival (DFS) and LRFS were 93.0, 84.8, and 93.6%, respectively. There was no significant difference between patients who received PMRT or not for the entire group. A nomogram was developed and validated to estimate the probability of 5-year LRFS based on five independent factors including age, primary tumor site, positive lymph nodes number, pathological T stage, and molecular subtype that were selected by a multivariate analysis of patients who did not receive PMRT in the primary cohort. According to the total nomogram risk scores, the entire patients were classified into low- (40.0%), moderate- (42.4%), and high-risk group (17.6%). The 5-year outcomes were significantly different among these three groups (P<0.001). In low-risk group, patients who received PMRT or not both achieved a favorable OS, DFS, and LRFS. In moderate-risk group, no differences in OS, DFS, and LRFS were observed between PMRT and no PMRT patients. In high-risk group, compared with no PMRT, PMRT resulted in significantly different OS (86.8 vs 83.9%, P = 0.050), DFS (77.2 vs 70.9%, P = 0.049), and LRFS (90.8 vs. 81.6%, P = 0.003). After PSM adjustment, there were no significant differences in OS, DFS, and LRFS in low-risk and moderate-risk groups. However, in the high-risk group, PMRT still resulted in significantly better OS, DFS and improved LRFS.ConclusionsThe proposed nomogram provides an individualized risk estimate of LRFS in patients with pT1-2N1M0 breast cancer. Risk-adapted PMRT for high-risk patients is a viable effective strategy.

2021 ◽  
Author(s):  
juanjuan Qiu ◽  
Li Xu ◽  
Yu Wang ◽  
Jia Zhang ◽  
Jiqiao Yang ◽  
...  

Abstract Background Although the results of gene testing can guide early breast cancer patients with HR+, HER2- to decide whether they need chemotherapy, there are still many patients worldwide whose problems cannot be solved well by genetic testing. Methods 144 735 patients with HR+, HER2-, pT1-3N0-1 breast cancer from the Surveillance, Epidemiology, and End Results database were included from 2010 to 2015. They were divided into chemotherapy (n = 38 392) and no chemotherapy (n = 106 343) group, and after propensity score matching, 23 297 pairs of patients were left. Overall survival (OS) and breast cancer-specific survival (BCSS) were tested by Kaplan–Meier plot and log-rank test and Cox proportional hazards regression model was used to identify independent prognostic factors. A nomogram was constructed and validated by C-index and calibrate curves. Patients were divided into high- or low-risk group according to their nomogram score using X-tile. Results Patients receiving chemotherapy had better OS before and after matching (p < 0.05) but BCSS was not significantly different between patients with and without chemotherapy after matching: hazard ratio (HR) 1.005 (95%CI 0.897, 1.126). Independent prognostic factors were included to construct the nomogram to predict BCSS of patients without chemotherapy. Patients in the high-risk group (score > 238) can get better OS HR 0.583 (0.507, 0.671) and BCSS HR 0.791 (0.663, 0.944) from chemotherapy but the low-risk group (score ≤ 238) cannot. Conclusion The well-validated nomogram and a risk stratification model was built. Patients in the high-risk group should receive chemotherapy while patients in low-risk group may be exempt from chemotherapy.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Yasuhiro Kumai ◽  
Takuya Kiyohara ◽  
Masahiro Kamouchi ◽  
Sohei Yoshimura ◽  
Hiroshi Sugimori ◽  
...  

Background and Purpose— ABCD 2 score has been developed to predict the early risk of stroke after transient ischemic attack (TIA). The aim of this study was to clarify whether ABCD 2 score predicts the occurrence of stroke in the long term after TIA. Methods— Fukuoka Stroke Registry (FSR) is a multicenter epidemiological study database on acute stoke. From June 2007 to June 2011, 496 (305 males, 70 ± 13 years of age) patients who had suffered from TIA and were hospitalized in the 7 stroke centers within 7 days after the onset of TIA were enrolled in this study. The patients were divided into three groups according to the risk: low-risk (ABCD 2 score 0-3; n=72), moderate-risk (4-5; n=229) and high-risk group (6-7; n=195). They were followed up prospectively for up to 3 years. Cox proportional hazard regression model was used to elucidate whether ABCD 2 score was a predictor for stroke after TIA after adjusting for confounding factors. Results— Among three groups, there were significant differences in age, hypertension, diabetes mellitus and the decrease in estimated glomerular filtration rate (P<0.01, significantly). During a mean follow-up of 1.3 years, Kaplan-Meier analysis demonstrated that the stroke rate in TIA patients was significantly lower in low-risk group than in moderate-risk or high-risk group (log rank test, p<0.001). The adjusted hazard ratios for stroke in patients with TIA increased with moderate-risk group (Hazard ratio [HR]: 3.47, 95% CI: 1.03-21.66, P<0.05) and high-risk group (HR: 4.46, 95% CI: 1.31-27.85, P<0.05), compared to low-risk group. Conclusions— The ABCD 2 score is able to predict the long-term risk of stroke after TIA.


2020 ◽  
Author(s):  
Ye Chen ◽  
Lei Dong ◽  
Minjing Li ◽  
Fei He ◽  
ChenHui Qiu ◽  
...  

Abstract Objective: This study aimed at establishing a novel nomogram predicting overall survival and investigating the survival benefit of various postoperative adjuvant treatments (POAT) in IIIA-N2 Non-small cell lung cancer (NSCLC) patients after surgery.Methods: Data of IIIA-N2 NSCLC patients between 2004 and 2016 were collected from the Surveillance, Epidemiology, and End Results (SEER). Patients were excluded if the information regarding follow-up time and clinicopathological features were incomplete. Through Univariate and multivariate analyses, independent prognostic factors were identified and integrated into the construction of nomogram. The survival benefit of POAT was evaluated in model-defined low-risk, intermediate-risk, and high-risk subgroups, respectively.Results: In total, 4389 patients were finally included for analysis. Patients’ age, sex, T stage, differentiation grade, examined lymph nodes number (ELN), metastatic lymph nodes number (MLN), and metastatic lymph nodes ratio (LNR) were identified as independent prognostic factors and were integrated into the construction of nomogram. The C-index and calibration curves indicated that the predictive performance of the nomogram was satisfactory. Patients were then categorized into three prognostic groups with the increasing risk of all-cause of death. The prognosis of patients receiving POAT (POCT or PORT plus POCT) and patients receiving surgery alone was comparable in low-risk group, while POCT could significantly prolong survival for IIIA-N2 NSCLC patients after surgery in moderate-risk and high-risk groups. Only patients in high-risk group could benefit from the combination of postoperative radiotherapy (PORT) and postoperative chemotherapy (POCT).Conclusion: In this large-cohort retrospective study, A survival-predicting nomogram and risk stratification model were established to estimate prognosis in IIIA-N2 NSCLC patients. Surgery alone was recommended as the first choice of treatment to patients in low-risk group. POCT was recommended for patients in moderate-risk group, and the combination of PORT and POCT was recommended for patients in high-risk group. This study may provide additional integration, introspection, and improvement for therapeutic decision-making.


Author(s):  
Xinshuang Yu ◽  
Peng Dong ◽  
Yu Yan ◽  
Fengjun Liu ◽  
Hui Wang ◽  
...  

Pancreatic cancer is a highly aggressive disease with poor prognosis. N6-methyladenosine (m6A) is critical for post-transcriptional modification of messenger RNA (mRNA) and long non-coding RNA (lncRNA). However, the m6A-associated lncRNAs (m6A-lncRNA) and their values in predicting clinical outcomes and immune microenvironmental status in pancreatic cancer patients remain largely unexplored. This study aimed to evaluate the importance of m6A-lncRNA and established a m6A-lncRNA signature for predicting immunotherapeutic response and prognosis of pancreatic cancer. The m6A-lncRNA co-expression networks were constructed using data from the TCGA and GTEx database. Based on the least absolute shrinkage and selection operator (LASSO) analysis, we constructed an 8 m6A-lncRNA signature risk model, and selection operator (LASSO) analysis, and stratified patients into the high- and low-risk groups with significant difference in overall survival (OS) (HR = 2.68, 95% CI = 1.74–4.14, P &lt; 0.0001). Patients in the high-risk group showed significantly reduced OS compared to patients in the low-risk group (P &lt; 0.001). The clinical characteristics and m6A-lncRNA risk scores were used to construct a nomogram which accurately predicted the OS in pancreatic cancer. TIMER 2.0 were used to investigate tumor immune infiltrating cells and its relationship with pancreatic cancer. CIBERSORT analysis revealed increased higher infiltration proportions of M0 and M2 macrophages, and lower infiltration of naive B cell, CD8+ T cell and Treg cells in the high-risk group. Compared to the low-risk group, functional annotation using ssGSEA showed that T cell infiltration and the differential immune-related check-point genes are expressed at low level in the high-risk group (P &lt; 0.05). In summary, our study constructed a novel m6A-associated lncRNAs signature to predict immunotherapeutic responses and provided a novel nomogram for the prognosis prediction of pancreatic cancer.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qian Zhang ◽  
Liping Lv ◽  
Ping Ma ◽  
Yangyang Zhang ◽  
Jiang Deng ◽  
...  

BackgroundPancreatic adenocarcinoma (PAAD) spreads quickly and has a poor prognosis. Autophagy research on PAAD could reveal new biomarkers and targets for diagnosis and treatment.MethodsAutophagy-related genes were translated into autophagy-related gene pairs, and univariate Cox regression was performed to obtain overall survival (OS)-related IRGPs (P&lt;0.001). LASSO Cox regression analyses were performed to construct an autophagy-related gene pair (ARGP) model for predicting OS. The Cancer Genome Atlas (TCGA)-PAAD cohort was set as the training group for model construction. The model predictive value was validated in multiple external datasets. Receiver operating characteristic (ROC) curves were used to evaluate model performance. Tumor microenvironments and immune infiltration were compared between low- and high-risk groups with ESTIMATE and CIBERSORT. Differentially expressed genes (DEGs) between the groups were further analyzed by Gene Ontology biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and used to identify potential small-molecule compounds in L1000FWD.ResultsRisk scores were calculated as follows: ATG4B|CHMP4C×(-0.31) + CHMP2B|MAP1LC3B×(0.30) + CHMP6|RIPK2 ×(-0.33) + LRSAM1|TRIM5×(-0.26) + MAP1LC3A|PAFAH1B2×(-0.15) + MAP1LC3A|TRIM21×(-0.08) + MET|MFN2×(0.38) + MET|MTDH×(0.47) + RASIP1|TRIM5×(-0.23) + RB1CC1|TPCN1×(0.22). OS was significantly shorter in the high-risk group than the low-risk group in each PAAD cohort. The ESTIMATE analysis showed no difference in stromal scores but a significant difference in immune scores (p=0.0045) and ESTIMATE scores (p=0.014) between the groups. CIBERSORT analysis showed higher naive B cell, Treg cell, CD8 T cell, and plasma cell levels in the low-risk group and higher M1 and M2 macrophage levels in the high-risk group. In addition, the results showed that naive B cells (r=-0.32, p&lt;0.001), Treg cells (r=-0.31, p&lt;0.001), CD8 T cells (r=-0.24, p=0.0092), and plasma cells (r=-0.2, p&lt;0.026) were statistically correlated with the ARGP risk score. The top 3 enriched GO-BPs were signal release, regulation of transsynaptic signaling, and modulation of chemical synaptic transmission, and the top 3 enriched KEGG pathways were the insulin secretion, dopaminergic synapse, and NF-kappa B signaling pathways. Several potential small-molecule compounds targeting ARGs were also identified.ConclusionOur results demonstrate that the ARGP-based model may be a promising prognostic indicator for identifying drug targets in patients with PAAD.


Author(s):  
Peng Gu ◽  
Lei Zhang ◽  
Ruitao Wang ◽  
Wentao Ding ◽  
Wei Wang ◽  
...  

Background: Female breast cancer is currently the most frequently diagnosed cancer in the world. This study aimed to develop and validate a novel hypoxia-related long noncoding RNA (HRL) prognostic model for predicting the overall survival (OS) of patients with breast cancer.Methods: The gene expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 200 hypoxia-related mRNAs were obtained from the Molecular Signatures Database. The co-expression analysis between differentially expressed hypoxia-related mRNAs and lncRNAs based on Spearman’s rank correlation was performed to screen out 166 HRLs. Based on univariate Cox regression and least absolute shrinkage and selection operator Cox regression analysis in the training set, we filtered out 12 optimal prognostic hypoxia-related lncRNAs (PHRLs) to develop a prognostic model. Kaplan–Meier survival analysis, receiver operating characteristic curves, area under the curve, and univariate and multivariate Cox regression analyses were used to test the predictive ability of the risk model in the training, testing, and total sets.Results: A 12-HRL prognostic model was developed to predict the survival outcome of patients with breast cancer. Patients in the high-risk group had significantly shorter median OS, DFS (disease-free survival), and predicted lower chemosensitivity (paclitaxel, docetaxel) compared with those in the low-risk group. Also, the risk score based on the expression of the 12 HRLs acted as an independent prognostic factor. The immune cell infiltration analysis revealed that the immune scores of patients in the high-risk group were lower than those of the patients in the low-risk group. RT-qPCR assays were conducted to verify the expression of the 12 PHRLs in breast cancer tissues and cell lines.Conclusion: Our study uncovered dozens of potential prognostic biomarkers and therapeutic targets related to the hypoxia signaling pathway in breast cancer.


2021 ◽  
Vol 8 (9) ◽  
pp. 2680
Author(s):  
Vaishali C. Shelgaonkar ◽  
Swatika P. Butey ◽  
Vishal R. Nandagawali

Background: Many scoring systems have been used to assess the morbidity and mortality of patients presenting with acute abdomen, of which Apache II (acute physiology and chronic health evaluation) score has been accepted widely. This study predicted the effectiveness of Apache II scoring system as a potential clinical and research tool which could be included as routine part of patient assessment to predict the morbidity and mortality in patients undergoing emergency gastrointestinal procedures.Methods: This study was conducted in the surgical intensive care unit of our tertiary care hospital. It was a prospective observational study done over a period of one year where we assessed the efficacy of Apache II score in eighty two patients.Results: The Apache II scores were divided into three categories, 0-15 low risk group, 16-30 moderate risk group and 31-45 high risk group. There were 25 patients in the low risk group with all being satisfactorily discharged. With 44 patients in the moderate risk group 13 expired (29.54% mortality) and out of 13 patients in the high risk group 11 patients died (84.61% mortality).Conclusions: In the present study the APACHE II scores have correlated well with the outcomes and ICU stay of the patient groups.


2022 ◽  
Vol 12 ◽  
Author(s):  
Xitao Wang ◽  
Xiaolin Dou ◽  
Xinxin Ren ◽  
Zhuoxian Rong ◽  
Lunquan Sun ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous malignancy. Single-cell sequencing (scRNA-seq) technology enables quantitative gene expression measurements that underlie the phenotypic diversity of cells within a tumor. By integrating PDAC scRNA-seq and bulk sequencing data, we aim to extract relevant biological insights into the ductal cell features that lead to different prognoses. Firstly, differentially expressed genes (DEGs) of ductal cells between normal and tumor tissues were identified through scRNA-seq data analysis. The effect of DEGs on PDAC survival was then assessed in the bulk sequencing data. Based on these DEGs (LY6D, EPS8, DDIT4, TNFSF10, RBP4, NPY1R, MYADM, SLC12A2, SPCS3, NBPF15) affecting PDAC survival, a risk score model was developed to classify patients into high-risk and low-risk groups. The results showed that the overall survival was significantly longer in the low-risk group (p &lt; 0.05). The model also revealed reliable predictive power in different subgroups of patients. The high-risk group had a higher tumor mutational burden (TMB) (p &lt; 0.05), with significantly higher mutation frequencies in KRAS and ADAMTS12 (p &lt; 0.05). Meanwhile, the high-risk group had a higher tumor stemness score (p &lt; 0.05). However, there was no significant difference in the immune cell infiltration scores between the two groups. Lastly, drug candidates targeting risk model genes were identified, and seven compounds might act against PDAC through different mechanisms. In conclusion, we have developed a validated survival assessment model, which acted as an independent risk factor for PDAC.


2021 ◽  
Author(s):  
Jinlong Huo ◽  
Shuang Shen ◽  
Chen Chen ◽  
Rui Qu ◽  
Youming Guo ◽  
...  

Abstract Background: Breast cancer(BC) is the most common tumour in women. Hypoxia stimulates metastasis in cancer and is linked to poor patient prognosis.Methods: We screened prognostic-related lncRNAs(Long Non-Coding RNAs) from the Cancer Genome Atlas (TCGA) data and constructed a prognostic signature based on hypoxia-related lncRNAs in BC.Results: We identified 21 differentially expressed lncRNAs associated with BC prognosis. Kaplan Meier survival analysis indicated a significantly worse prognosis for the high-risk group(P<0.001). Moreover, the ROC-curve (AUC) of the lncRNAs signature was 0.700, a performance superior to other traditional clinicopathological characteristics. Gene set enrichment analysis (GSEA) showed many immune and cancer-related pathways and in the low-risk group patients. Moreover, TCGA revealed that functions including activated protein C (APC)co-inhibition, Cinnamoyl CoA reductase(CCR),check-point pathways, cytolytic activity, human leukocyte antigen (HLA), inflammation-promotion, major histocompatibility complex(MHC) class1, para-inflammation, T cell co-inhibition, T cell co-stimulation, and Type Ⅰ and Ⅱ Interferons (IFN) responses were significantly different in the low-risk and high-risk groups. Immune checkpoint molecules such as ICOS, IDO1, TIGIT, CD200R1, CD28, PDCD1(PD-1), were also expressed differently between the two risk groups. The expression of m6A-related mRNA indicated that YTHDC1, RBM15, METTL3, and FTO were significantly between the high and low-risk groups.Additionally, immunotherapy in patients with BC from the low-risk group yielded a higher frequency of clinical responses to anti-PD-1/PD-L1 therapy or a combination of anti-PD-1/PD-L1and anti-CTLA4 therapies.Except for lapatinib, the results also show that a high-risk score is related to a higher half-maximal inhibitory concentration (IC50) of chemotherapy drugs.Conclusion: A novel hypoxia-related lncRNAs signature may serve as a prognostic model for BC.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3128-3128 ◽  
Author(s):  
María José Terol ◽  
Ana Isabel Teruel ◽  
Paula Amat ◽  
Danella Elaluf ◽  
Mar Tormo ◽  
...  

Abstract Abstract 3128 Background: follicular lymphoma is an incurable, long-lasting disease with an heterogeneous outcome. Several prognostic systems have been proposed, and recently a new one, the FLIPI2 score based on five parameters has been published. However, in order to confirm its prognostic utility, further studies at other centers are highly recommendable. Aim: to validate the new FLIPI2 score in independent series of follicular lymphoma patients diagnosed at our institution between February 1990 and July 2010. Patients and methods. We considered 180 patients consecutively diagnosed with follicular diagnosis in the period described and from whom all variables required were available. The variables included were: beta2microglobulin higher than the upper normal value, longest diameter of the largest involved node longer than 6 cm, bone marrow infiltration, hemoglobin level lower than 120 g/L and age older than 60 years (one point if present). Three risk groups were identified: low risk (0 points), intermediate risk (1 -2) and high risk (3 or more) Progression-free survival was measured from date of treatment until date of progression or death from any cause. Continuous variables were summarized as median and range, categorical variables reported as counts, and PFS and OS carried out using the Kaplan-Meier method and curves compared by the log-rank test. Results: median age was 55 years (range, 24 to 77), male sex 92 (51%), Ann Arbor Stage I-II: 32(18%), III-IV: 143 (82%), age > 60 y 70 (39%), Hb < 120 g/L 38 (21%), β2microglobulin > UNV: 45 (25%), LDH > UNV: 34 (19%), bone marrow infiltration 82 (48%), longer diameter of the largest involved node > 6 cm 64 (36%). 47 patients (26%) received rituximab-containing regimens and 124 received conventional chemotherapy regimens (pre-rituximab era). Median follow-up of the series was 66.9 months (range,1.3-221). Using the FLIPI score (n=162) 58 patients (36%) were in the low risk group, 54 (33%) were in the intermediate group and 50 (31%) in the high risk group. Using the FLIPI2 (n=180) 36 patients (20%) were in the low risk group, 103 (57%) in the intermediate group and 41 (23%) in the high risk group. According to FLIPI 5y- PFS rate was 79% for the low risk group, 63% for the intermediate group and 32% for the high risk group, p < 0.001. According to FLIPI2 score, 5y-PFS rate was 82% for the low risk, 54% for the intermediate and 43% for the high risk groups, p=0.017. Concerning OS, applying the FLIPI, 5y-OS rate for the low, intermediate and high risk groups were 94%m 84% and 64%, respectively, p=0.003. Using the FLIPI2, 5y-OS for the low, intermediate and high risk groups were 96%, 80% and 67% respectively, p=0.006. Conclusions: in our experience the FLIPI2 score is a reproducible prognostic index in patients with follicular lymphoma although the FLIPI score seems to discriminate better between groups than the FLIPI2 score. Disclosures: No relevant conflicts of interest to declare.


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