Radiomic Score as a Potential Imaging Biomarker for Predicting Survival in Patients With Cervical Cancer

ObjectivesAccurate prediction of prognosis will help adjust or optimize the treatment of cervical cancer and benefit the patients. We aimed to investigate the incremental value of radiomics when added to the FIGO stage in predicting overall survival (OS) in patients with cervical cancer.MethodsThis retrospective study included 106 patients with cervical cancer (FIGO stage IB1–IVa) between October 2017 and May 2019. Patients were randomly divided into a training cohort (n = 74) and validation cohort (n = 32). All patients underwent contrast-enhanced computed tomography (CT) prior to treatment. The ITK-SNAP software was used to delineate the region of interest on pre-treatment standard-of-care CT scans. We extracted 792 two-dimensional radiomic features by the Analysis Kit (AK) software. Pearson correlation coefficient analysis and Relief were used to detect the most discriminatory features. The radiomic signature (i.e., Radscore) was constructed via Adaboost with Leave-one-out cross-validation. Prognostic models were built by Cox regression model using Akaike information criterion (AIC) as the stopping rule. A nomogram was established to individually predict the OS of patients. Patients were then stratified into high- and low-risk groups according to the Youden index. Kaplan–Meier curves were used to compare the survival difference between the high- and low-risk groups.ResultsSix textural features were identified, including one gray-level co-occurrence matrix feature and five gray-level run-length matrix features. Only the FIGO stage and Radscore were independent risk factors associated with OS (p < 0.05). The C-index of the FIGO stage in the training and validation cohorts was 0.703 (95% CI: 0.572–0.834) and 0.700 (95% CI: 0.526–0.874), respectively. Correspondingly, the C-index of Radscore was 0.794 (95% CI: 0.707–0.880) and 0.754 (95% CI: 0.623–0.885). The incorporation of the FIGO stage and Radscore achieved better performance, with a C-index of 0.830 (95% CI: 0.738–0.922) and 0.772 (95% CI: 0.615–0.929), respectively. The nomogram based on the FIGO stage and Radscore could individually predict the OS probability with good discrimination and calibration. The high-risk patients had shorter OS compared with the low-risk patients (p < 0.05).ConclusionRadiomics has the potential for noninvasive risk stratification and may improve the prediction of OS in patients with cervical cancer when added to the FIGO stage.

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Comparison of adenocarcinoma and adenosquamous carcinoma prognoses in Chinese patients with FIGO stage IB-IIA cervical cancer following radical surgery

10.21203/rs.3.rs-20226/v2 ◽

2020 ◽

Author(s):

Xiaojing Zhang ◽

Zunfu Lv ◽

Xiaoxian Xu ◽

Zhuomin Yin ◽

hanmei Lou

Keyword(s):

Cervical Cancer ◽

Cox Regression ◽

Adenosquamous Carcinoma ◽

Risk Groups ◽

Figo Stage ◽

Chinese Patients ◽

Survival Outcomes ◽

Intermediate Risk ◽

Stage Ib ◽

Risk Patients

Abstract Background: To compare adenocarcinoma (AC) and adenosquamous carcinoma (ASC) prognoses in patients with FIGO stage IB–IIA cervical cancer who underwent radical hysterectomy. Methods. We performed a retrospective analysis of 240 patients with AC and 130 patients with ASC. Kaplan–Meier curves, Cox regression models, and log-rank tests were used for statistical analysis. Results: Patients with ASC had higher frequencies of lymphovascular space invasion (LVSI) and serum squamous cell carcinoma antigen (SCC-Ag) > 5 ng/ml (p=0.049 and p=0.013, respectively); moreover, they were much older (P=0.029) than patients with AC. There were no clinically significant differences in overall survival (OS) between the groups. When stratified into three risk groups based on clinicopathological features, survival outcomes did not differ between patients with AC and those with ASC in any risk group. Multivariate analysis showed that lymph node metastasis (LNM) was an independent risk factor for recurrence-free survival (RFS) and OS in patients with AC and in patients with ASC. Carcinoembryonic antigen (CEA) > 5 ng/ml and SCC-Ag > 5 ng/ml were independent predictors of RFS and OS in patients with AC. In addition, among those stratified as intermediate-risk, patients with ASC who received concurrent chemoradiotherapy (CCRT) had significantly better RFS and OS (P=0.036 and P=0.047, respectively). Conclusions: We did not find evidence to suggest that AC and ASC subtypes of cervical cancer were associated with different survival outcomes. CCRT is beneficial for survival in intermediate-risk patients with ASC, but not in those with AC. Serum tumour markers can assist in evaluating prognosis and in providing additional information for patient-tailored therapy for cervical AC.

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Comparison of adenocarcinoma and adenosquamous carcinoma prognoses in Chinese patients with FIGO stage IB-IIA cervical cancer following radical surgery

10.21203/rs.3.rs-20226/v3 ◽

2020 ◽

Author(s):

Xiaojing Zhang ◽

Zunfu Lv ◽

Xiaoxian Xu ◽

Zhuomin Yin ◽

hanmei Lou

Keyword(s):

Cervical Cancer ◽

Cox Regression ◽

Adenosquamous Carcinoma ◽

Risk Groups ◽

Figo Stage ◽

Chinese Patients ◽

Survival Outcomes ◽

Intermediate Risk ◽

Stage Ib ◽

Risk Patients

Abstract Background. To compare adenocarcinoma (AC) and adenosquamous carcinoma (ASC) prognoses in patients with FIGO stage IB–IIA cervical cancer who underwent radical hysterectomy.Methods. We performed a retrospective analysis of 240 patients with AC and 130 patients with ASC. Kaplan–Meier curves, Cox regression models, and log-rank tests were used for statistical analysis.Results. Patients with ASC had higher frequencies of lymphovascular space invasion (LVSI) and serum squamous cell carcinoma antigen (SCC-Ag) > 5 ng/ml (p=0.049 and p=0.013, respectively); moreover, they were much older (P=0.029) than patients with AC. There were no clinically significant differences in overall survival (OS) between the groups. When stratified into three risk groups based on clinicopathological features, survival outcomes did not differ between patients with AC and those with ASC in any risk group. Multivariate analysis showed that lymph node metastasis (LNM) was an independent risk factor for recurrence-free survival (RFS) and OS in patients with AC and in patients with ASC. Carcinoembryonic antigen (CEA) > 5 ng/ml and SCC-Ag > 5 ng/ml were independent predictors of RFS and OS in patients with AC. In addition, among those stratified as intermediate-risk, patients with ASC who received concurrent chemoradiotherapy (CCRT) had significantly better RFS and OS (P=0.036 and P=0.047, respectively). Conclusions. We did not find evidence to suggest that AC and ASC subtypes of cervical cancer were associated with different survival outcomes. CCRT is beneficial for survival in intermediate-risk patients with ASC, but not in those with AC. Serum tumour markers can assist in evaluating prognosis and in providing additional information for patient-tailored therapy for cervical AC.

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Development and Verification of the Hypoxia- and Immune-Associated Prognostic Signature for Pancreatic Ductal Adenocarcinoma

Frontiers in Immunology ◽

10.3389/fimmu.2021.728062 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dongjie Chen ◽

Hui Huang ◽

Longjun Zang ◽

Wenzhe Gao ◽

Hongwei Zhu ◽

...

Keyword(s):

High Risk ◽

Pancreatic Ductal Adenocarcinoma ◽

Risk Score ◽

Cox Regression ◽

Pearson Correlation ◽

Risk Groups ◽

Low Risk ◽

Ductal Adenocarcinoma ◽

Prognostic Signature ◽

Score Model

We aim to construct a hypoxia- and immune-associated risk score model to predict the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). By unsupervised consensus clustering algorithms, we generate two different hypoxia clusters. Then, we screened out 682 hypoxia-associated and 528 immune-associated PDAC differentially expressed genes (DEGs) of PDAC using Pearson correlation analysis based on the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression project (GTEx) dataset. Seven hypoxia and immune-associated signature genes (S100A16, PPP3CA, SEMA3C, PLAU, IL18, GDF11, and NR0B1) were identified to construct a risk score model using the Univariate Cox regression and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, which stratified patients into high- and low-risk groups and were further validated in the GEO and ICGC cohort. Patients in the low-risk group showed superior overall survival (OS) to their high-risk counterparts (p < 0.05). Moreover, it was suggested by multivariate Cox regression that our constructed hypoxia-associated and immune-associated prognosis signature might be used as the independent factor for prognosis prediction (p < 0.001). By CIBERSORT and ESTIMATE algorithms, we discovered that patients in high-risk groups had lower immune score, stromal score, and immune checkpoint expression such as PD-L1, and different immunocyte infiltration states compared with those low-risk patients. The mutation spectrum also differs between high- and low-risk groups. To sum up, our hypoxia- and immune-associated prognostic signature can be used as an approach to stratify the risk of PDAC.

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Identification of the Pyroptosis-related Signature for Predicting Prognosis in Cervical Cancer

10.21203/rs.3.rs-870182/v1 ◽

2021 ◽

Author(s):

Cankun Zhou ◽

Chaomei Li ◽

Yuhua Zheng ◽

Xiaochun Liu

Keyword(s):

Cervical Cancer ◽

Tumor Microenvironment ◽

Cox Regression ◽

Experimental Studies ◽

Risk Groups ◽

Core Gene ◽

Low Risk ◽

Prognostic Signature ◽

Cox Regression Analysis ◽

Immune Infiltration

Abstract Background: Cervical cancer (CC) is one of the most common malignancies in gynecology. There is still a lack of specific biomarkers for the diagnosis and prognosis of CC. Pyroptosis is one of the methods of programmed cell death, and its various components are related to the occurrence, invasion, and metastasis of tumors. However, the role of pyroptosis in CC has not yet been elucidated.Methods: This study focuses on the development of a prognostic signature associated with pyroptosis for CC patients using integrated bioinformatics to elucidate the relationship between the signature and the tumor microenvironment and immune response.Results: We identified a prognostic signature based on eight pyroptosis-related genes (PRGs), with better prognostic survival in the low-risk group (P<0.05) and AUC values greater than 0.7. The results of the multi-factor Cox regression analysis indicated that the signature could be used as an independent prognostic factor, and both the DCA and the Nomogram suggested that the prognostic signature had good predictive power. Interestingly, this prognostic signature can also be applied to multiple tumors. In addition, the tumor microenvironment and immune infiltration status were significantly different between high and low-risk groups (P<0. 05). The core gene GZMB was screened and the CC-associated GZMB/ miR-378a/TRIM52-AS1 regulatory axis was constructed.Conclusion: The study successfully established the prognostic signature based on eight PRGs and reflected their tumor microenvironment and immune infiltration. The GZMB/ miR-378a/TRIM52-AS1 regulatory axis may play an important regulatory role in the development of CC, and further experimental studies are needed to validate these results subsequently.

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Immune-Related Four-lncRNA Signature for Patients with Cervical Cancer

BioMed Research International ◽

10.1155/2020/3641231 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Jianfeng Zheng ◽

Benben Cao ◽

Xia Zhang ◽

Zheng Niu ◽

Jinyi Tong

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Immune Cell ◽

Risk Group ◽

Pearson Correlation ◽

Characteristic Curve ◽

Risk Groups ◽

High Risk Group ◽

Low Risk ◽

Gynecological Malignancy

Cervical cancer (CC) is a common gynecological malignancy for which prognostic and therapeutic biomarkers are urgently needed. The signature based on immune-related lncRNAs (IRLs) of CC has never been reported. This study is aimed at establishing an IRL signature for patients with CC. A cohort of 326 CC and 21 normal tissue samples with corresponding clinical information was included in this study. Twenty-eight IRLs were collected according to the Pearson correlation analysis between the immune score and lncRNA expression ( p < 0.01 ). Four IRLs (BZRAP1-AS1, EMX2OS, ZNF667-AS1, and CTC-429P9.1) with the most significant prognostic values ( p < 0.05 ) were identified which demonstrated an ability to stratify patients into the low-risk and high-risk groups by developing a risk score model. It was observed that patients in the low-risk group showed longer overall survival (OS) than those in the high-risk group in the training set, valid set, and total set. The area under the curve (AUC) of the receiver operating characteristic curve (ROC curve) for the four-IRL signature in predicting the one-, two-, and three-year survival rates was larger than 0.65. In addition, the low-risk and high-risk groups displayed different immune statuses in GSEA. These IRLs were also significantly correlated with immune cell infiltration. Our results showed that the IRL signature had a prognostic value for CC. Meanwhile, the specific mechanisms of the four IRLs in the development of CC were ascertained preliminarily.

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The Landscape of Glycosyltransferase Gene Signature for Overall Survival Prediction in Hepatocellular Carcinoma

10.21203/rs.3.rs-114747/v1 ◽

2020 ◽

Author(s):

Qiang Cai ◽

Shizhe Yu ◽

Jian Zhao ◽

Duo Ma ◽

Long Jiang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Risk Score ◽

Prognostic Value ◽

Cox Regression ◽

Risk Groups ◽

Gene Signature ◽

Low Risk ◽

Regression Analyses ◽

Risk Patients

Abstract Background: Hepatocellular carcinoma (HCC) is heterogeneous disease occurring in the background of chronic liver diseases. The role of glycosyltransferase (GT) genes have recently been the focus of research associating with the development of tumors. However, the prognostic value of GT genes in HCC remains not elucidated. This study aimed to demonstrate the GT genes related to the prognosis of HCC through bioinformatics analysis.Methods: The GT genes signatures were identified from the training set of The Cancer Genome Atlas (TCGA) dataset using univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Then, we analyzed the prognostic value of GT genes signatures related to the overall survival (OS) of HCC patients. A prognostic model was constructed, and the risk score of each patient was calculated as formula, which divided HCC patients into high- and low-risk groups. Kaplan-Meier (K-M) and Receiver operating characteristic (ROC) curves were used to assess the OS of HCC patients. The prognostic value of GT genes signatures was further investigated in the validation set of TCGA database. Univariate and multivariate Cox regression analyses were performed to demonstrate the independent factors on OS. Finally, we utilized the gene set enrichment analysis (GSEA) to annotate the function of these genes between the two risk categories. Results: In this study, we identified and validated 4 GT genes as the prognostic signatures. The K-M analysis showed that the survival rate of the high-risk patients was significantly lower than that of the low-risk patients. The risk score calculated with 4 gene signatures could predict OS for 3-, 5-, and 7-year in patients with HCC, revealing the prognostic ability of these gene signature. In addition, Multivariate Cox regression analyses indicated that the risk score was an independent prognostic factor for HCC. Functional analysis further revealed that immune-related pathways were enriched, and immune status in HCC were different between the two risk groups.Conclusion: In conclusion, a novel GT genes signature can be used for prognostic prediction in HCC. Thus, targeting GT genes may be a therapeutic alternative for HCC.

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A new look at the IDEA classification: Defining novel predictive and prognostic markers in stage III colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.845 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 845-845

Author(s):

Ofer Margalit ◽

Ronac Mamtani ◽

Yu-Xiao Yang ◽

Kim Anna Reiss ◽

Talia Golan ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Cox Regression ◽

Secondary Analysis ◽

Risk Groups ◽

Low Risk ◽

Stage Iii ◽

Stage Iii Colon Cancer ◽

Risk Patients ◽

Doublet Chemotherapy

845 Background: The IDEA pooled analysis compared 3 to 6 months of adjuvant chemotherapy for newly defined low- and high-risk stage III colon cancer patients, suggesting low-risk patients may be offered only 3 months of treatment. We aimed to evaluate the benefit of monotherapy vs doublet chemotherapy in low and high IDEA risk groups. Methods: Using the NCDB (2004-2014) we identified 56,728 and 47,557 individuals as low and high IDEA risk groups, respectively. We used multivariate COX regression to evaluate the magnitude of survival differences between IDEA risk groups, according to treatment intensity (doublet vs monotherapy). In a secondary analysis, we examined the predictive value of subgroups of age. Results: Low and high IDEA risk groups derived similar benefit from doublet chemotherapy compared to monotherapy, with hazard ratios of 0.83 (95%CI 0.79-0.86) and 0.80 (95%CI 0.78-0.83), respectively. The only subpopulations that did not benefit from doublet chemotherapy were low-risk patients above the age of 72 (HR = 0.95, 95%CI 0.90-1.01) and high-risk patients above the age of 85 (HR = 0.90, 95%CI 0.77-1.05). Conclusions: IDEA risk classification does not predict benefit from doublet chemotherapy in stage III colon cancer. However, omission of oxaliplatin can be considered in IDEA low-risk patients above the age of 72.

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Long-term colorectal cancer incidence after adenoma removal and the effects of surveillance on incidence: a multicentre, retrospective, cohort study

Gut ◽

10.1136/gutjnl-2019-320036 ◽

2020 ◽

Vol 69 (9) ◽

pp. 1645-1658 ◽

Cited By ~ 5

Author(s):

Amanda J Cross ◽

Emma C Robbins ◽

Kevin Pack ◽

Iain Stenson ◽

Paula L Kirby ◽

...

Keyword(s):

Colorectal Cancer ◽

High Risk ◽

General Population ◽

Cox Regression ◽

Risk Groups ◽

Low Risk ◽

Intermediate Risk ◽

Hazard Ratios ◽

Risk Patients ◽

Time Varying Covariates

ObjectivePostpolypectomy colonoscopy surveillance aims to prevent colorectal cancer (CRC). The 2002 UK surveillance guidelines define low-risk, intermediate-risk and high-risk groups, recommending different strategies for each. Evidence supporting the guidelines is limited. We examined CRC incidence and effects of surveillance on incidence among each risk group.DesignRetrospective study of 33 011 patients who underwent colonoscopy with adenoma removal at 17 UK hospitals, mostly (87%) from 2000 to 2010. Patients were followed up through 2016. Cox regression with time-varying covariates was used to estimate effects of surveillance on CRC incidence adjusted for patient, procedural and polyp characteristics. Standardised incidence ratios (SIRs) compared incidence with that in the general population.ResultsAfter exclusions, 28 972 patients were available for analysis; 14 401 (50%) were classed as low-risk, 11 852 (41%) as intermediate-risk and 2719 (9%) as high-risk. Median follow-up was 9.3 years. In the low-risk, intermediate-risk and high-risk groups, CRC incidence per 100 000 person-years was 140 (95% CI 122 to 162), 221 (195 to 251) and 366 (295 to 453), respectively. CRC incidence was 40%–50% lower with a single surveillance visit than with none: hazard ratios (HRs) were 0.56 (95% CI 0.39 to 0.80), 0.59 (0.43 to 0.81) and 0.49 (0.29 to 0.82) in the low-risk, intermediate-risk and high-risk groups, respectively. Compared with the general population, CRC incidence without surveillance was similar among low-risk (SIR 0.86, 95% CI 0.73 to 1.02) and intermediate-risk (1.16, 0.97 to 1.37) patients, but higher among high-risk patients (1.91, 1.39 to 2.56).ConclusionPostpolypectomy surveillance reduces CRC risk. However, even without surveillance, CRC risk in some low-risk and intermediate-risk patients is no higher than in the general population. These patients could be managed by screening rather than surveillance.

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Identification of HCC Subtypes With Different Prognosis and Metabolic Patterns Based on Mitophagy

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.799507 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yao Wang ◽

Zhen Wang ◽

Jingjing Sun ◽

Yeben Qian

Keyword(s):

Roc Curve ◽

Cox Regression ◽

Cholesterol Biosynthesis ◽

Principal Component ◽

Risk Groups ◽

Prognostic Indicator ◽

R Package ◽

Low Risk ◽

Rank Test ◽

Risk Patients

Background: Mitophagy is correlated with tumor initiation and development of malignancy. However, HCC heterogeneity with reference to mitophagy has yet not been systematically explored.Materials and Methods: Mitophagy-related, glycolysis-related, and cholesterol biosynthesis-related gene sets were obtained from the Reactome database. Mitophagy-related and metabolism-related subtypes were identified using the ConsensusClusterPlus algorithm. Univariate Cox regression was analysis was performed to identify prognosis-related mitophagy regulators. Principal component analysis (PCA) was used to create composite measures of the prognosis-related mitophagy regulators (mitophagyscore). Individuals with a mitophagyscore higher or lower than the median value were classified in high- or low-risk groups. Kaplan-Meier survival and ROC curve analyses were utilized to evaluate the prognostic value of the mitophagyscore. The nomogram and calibration curves were plotted using the“rms” R package. The package “limma” was used for differential gene expression analysis. Differentially expressed genes (DEGs) between high- and low-risk groups were used as queries in the CMap database. R package “pRRophetic” and Genomics of Drug Sensitivity in Cancer (GDSC) database were used to determine the sensitivity of 21 previously reported anti-HCC drugs.Results: Three distinct HCC subtypes with different mitophagic accumulation (low, high, and intermediate mitophagy subtypes) were identified. High mitophagy subtype had the worst outcome and highest glycolysis level. The lowest degree of hypoxia and highest cholesterol biosynthesis was observed in the low mitophagy subtype; oncogenic dedifferentiation level in the intermediate mitophagy subtype was the lowest. Mitophagyscore could serve as a novel prognostic indicator for HCC.High-risk patients had a poorer prognosis (log-rank test, p < 0.001). The area under the ROC curve for mitophagyscore in 1-year survival was 0.77 in the TCGA cohort and 0.75 in the ICGC cohort. Nine candidate small molecules which were potential drugs for HCC treatment were identified from the CMap database. A decline in the sensitivity towards 21 anti-HCC drugs was observed in low-risk patients by GDSC database. We also identified a novel key gene, SPP1, which was highly associated with different mitophagic subtypes.Conclusion: Based on bioinformatic analyses, we systematically examined the HCC heterogeneity with reference to mitophagy and observed three distinct HCC subtypes having different prognoses and metabolic patterns.

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Comparison of adenocarcinoma and adenosquamous carcinoma prognoses in Chinese patients with FIGO stage IB-IIA cervical cancer following radical surgery

10.21203/rs.3.rs-20226/v1 ◽

2020 ◽

Author(s):

hanmei Lou ◽

Xiaojing Zhang ◽

Zunfu Lv ◽

Xiaoxian Xu ◽

Zhuomin Yin

Keyword(s):

Cervical Cancer ◽

Cox Regression ◽

Adenosquamous Carcinoma ◽

Risk Groups ◽

Figo Stage ◽

Chinese Patients ◽

Survival Outcomes ◽

Intermediate Risk ◽

Additional Information ◽

Stage Ib

Abstract Objective To compare adenocarcinoma (AC) and adenosquamous carcinoma (ASC) prognoses in patients with FIGO stage IB–IIA cervical cancer who underwent radical hysterectomy. Methods We performed a retrospective analysis of 240 patients with AC and 130 patients with ASC. Kaplan–Meier curves, Cox regression models, and log-rank tests were used for statistical analysis. Results Patients with ASC had higher frequencies of lymphovascular space invasion (LVSI) and serum squamous cell carcinoma antigen (SCC-Ag) >5 ng/ml ( p =0.049 and p =0.013, respectively); moreover, they were much older ( P =0.029) than patients with AC. There were no clinically significant differences in overall survival between the groups. When stratified into three risk groups based on clinicopathological features, survival outcomes did not differ between patients with AC and those with ASC in the three risk groups. Multivariate analysis showed that lymph node metastasis (LNM) was an independent risk factor for RFS and OS in patients with AC and in patients with ASC. Carcinoembryonic antigen (CEA) >5 ng/ml and SCC-Ag >5 ng/ml were independent risk factors for RFS and OS in patients with AC. In addition, among those stratified as intermediate-risk, patients with ASC who received concurrent chemoradiotherapy (CCRT) had a significantly better RFS and OS ( P =0.036, and P =0.047 for RFS and OS, respectively). Conclusion We did not find evidence to suggest that AC and ASC subtypes of cervical cancer were associated with different survival outcomes. CCRT is beneficial to survival for intermediate-risk-group patients with ASC, but not those with AC. Serum tumour markers can assist in evaluating prognosis and in providing additional information for patient-tailored therapy for cervical AC.

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