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Association of MRI-derived radiomic biomarker with disease-free survival in patients with early-stage cervical cancer.

ABSTRACT: Pre-treatment survival prediction plays a key role in many diseases. We aimed to determine the prognostic value of pre-treatment Magnetic Resonance Imaging (MRI) based radiomic score for disease-free survival (DFS) in patients with early-stage (IB-IIA) cervical cancer. Methods: A total of 248 patients with early-stage cervical cancer underwent radical hysterectomy were included from two institutions between January 1, 2011 and December 31, 2017, whose MR imaging data, clinicopathological data and DFS data were collected. Patients data were randomly divided into the training cohort (n = 166) and the validation cohort (n=82). Radiomic features were extracted from the pre-treatment T2-weighted (T2w) and contrast-enhanced T1-weighted (CET1w) MR imagings for each patient. Least absolute shrinkage and selection operator (LASSO) regression and Cox proportional hazard model were applied to construct radiomic score (Rad-score). According to the cutoff of Rad-score, patients were divided into low- and high- risk groups. Pearson's correlation and Kaplan-Meier analysis were used to evaluate the association of Rad-score with DFS. A combined model incorporating Rad-score, lymph node metastasis (LNM) and lymphovascular space invasion (LVI) by multivariate Cox proportional hazard model was constructed to estimate DFS individually. Results: Higher Rad-scores were significantly associated with worse DFS in the training and validation cohorts (P<0.001 and P=0.011, respectively). The Rad-score demonstrated better prognostic performance in estimating DFS (C-index, 0.753; 95% CI: 0.696-0.805) than the clinicopathological features (C-index, 0.632; 95% CI: 0.567-0.700). However, the combined model showed no significant improvement (C-index, 0.714; 95%CI: 0.642-0.784). Conclusion: The results demonstrated that MRI-derived Rad-score can be used as a prognostic biomarker for patients with early-stage (IB-IIA) cervical cancer, which can facilitate clinical decision-making.

SUBMITTER: Fang J

PROVIDER: S-EPMC7019161 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association of MRI-derived radiomic biomarker with disease-free survival in patients with early-stage cervical cancer.

Fang Jin J Zhang Bin B Wang Shuo S Jin Yan Y Wang Fei F Ding Yingying Y Chen Qiuying Q Chen Liting L Li Yueyue Y Li Minmin M Chen Zhuozhi Z Liu Lizhi L Liu Zhenyu Z Tian Jie J Zhang Shuixing S

Theranostics 20200116 5

Pre-treatment survival prediction plays a key role in many diseases. We aimed to determine the prognostic value of pre-treatment Magnetic Resonance Imaging (MRI) based radiomic score for disease-free survival (DFS) in patients with early-stage (IB-IIA) cervical cancer. <b>Methods:</b> A total of 248 patients with early-stage cervical cancer underwent radical hysterectomy were included from two institutions between January 1, 2011 and December 31, 2017, whose MR imaging data, clinicopathological ...[more]

PMID: 32089742

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Project description:ObjectiveTo examine the association between surgical volume and survival of women with early-stage cervical cancer who underwent radical hysterectomy.MethodsThis is a nationwide multicenter retrospective study examining consecutive women with clinical stage IB1-IIB cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy from 2004 to 2008 (N=5,964). The surgical volume per site over the 5-year period was defined as low-volume (fewer than 32 surgeries, 46 [39.7%] institutions, n=649 [10.9%]), mid-volume (32-104 surgeries, 60 [51.7%] institutions, n=3,662 [61.4%]), and high-volume (105 surgeries or more, 10 [8.6%] institutions, n=1,653 [27.7%]). Surgical volume-specific survival was examined with multivariable analysis and propensity score matching.ResultsThe median number of surgeries per site was 44 (interquartile range, 17-65). The 5-year disease-free survival rates among stage IB1-IIB disease were 77.2%, 79.9%, and 84.5% for low-, mid-, and high-volume groups, respectively. On multivariable analysis, women in high-volume centers had a decreased risk of recurrence (adjusted hazard ratio [HR] 0.69, 95% CI 0.58-0.82, P<.001) and all-cause mortality (adjusted HR 0.73, 95% CI 0.59-0.90, P=.003) compared with those in mid-volume centers. Specifically, women in high-volume centers had a decreased risk of local recurrence (adjusted HR 0.62, 95% CI 0.49-0.78, P<.001) but not distant recurrence (adjusted HR 0.85, 95% CI 0.67-1.06, P=.142) compared with those in mid-volume centers. Among 1,700 women with clinical stage IB1 disease treated with surgery alone, surgery at high-volume centers was associated with a decreased risk of recurrence (adjusted HR 0.45, 95% CI 0.25-0.79, P=.006) and all-cause mortality (adjusted HR 0.29, 95% CI 0.11-0.76, P=.013) compared with surgery at mid-volume centers on multivariable analysis. After propensity score matching, surgery at high-volume centers remained an independent prognostic factor for decreased recurrence (adjusted HR 0.69, 95% CI 0.57-0.84, P<.001) and all-cause mortality (adjusted HR 0.75, 95% CI 0.59-0.95, P=.016) compared with surgery at mid- and low-volume centers on multivariable analysis.ConclusionHospital volume for radical hysterectomy may be a prognostic factor for early-stage cervical cancer. Surgery at high-volume centers is associated with decreased local recurrence risk and improved survival.

Project description:BackgroundAccurate pretherapeutic prognostication is important for tailoring treatment in cervical cancer (CC).PurposeTo investigate whether pretreatment MRI-based radiomic signatures predict disease-specific survival (DSS) in CC.Study typeRetrospective.PopulationCC patients (n = 133) allocated into training(T) (nT = 89)/validation(V) (nV = 44) cohorts.Field strength/sequenceT2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) at 1.5T or 3.0T.AssessmentRadiomic features from segmented tumors were extracted from T2WI and DWI (high b-value DWI and apparent diffusion coefficient (ADC) maps).Statistical testsRadiomic signatures for prediction of DSS from T2WI (T2rad ) and T2WI with DWI (T2 + DWIrad ) were constructed by least absolute shrinkage and selection operator (LASSO) Cox regression. Area under time-dependent receiver operating characteristics curves (AUC) were used to evaluate and compare the prognostic performance of the radiomic signatures, MRI-derived maximum tumor size ≤/> 4 cm (MAXsize ), and 2018 International Federation of Gynecology and Obstetrics (FIGO) stage (I-II/III-IV). Survival was analyzed using Cox model estimating hazard ratios (HR) and Kaplan-Meier method with log-rank tests.ResultsThe radiomic signatures T2rad and T2 + DWIrad yielded AUCT /AUCV of 0.80/0.62 and 0.81/0.75, respectively, for predicting 5-year DSS. Both signatures yielded better or equal prognostic performance to that of MAXsize (AUCT /AUCV : 0.69/0.65) and FIGO (AUCT /AUCV : 0.77/0.64) and were significant predictors of DSS after adjusting for FIGO (HRT /HRV for T2rad : 4.0/2.5 and T2 + DWIrad : 4.8/2.1). Adding T2rad and T2 + DWIrad to FIGO significantly improved DSS prediction compared to FIGO alone in cohort(T) (AUCT 0.86 and 0.88 vs. 0.77), and FIGO with T2 + DWIrad tended to the same in cohort(V) (AUCV 0.75 vs. 0.64, p = 0.07). High radiomic score for T2 + DWIrad was significantly associated with reduced DSS in both cohorts.Data conclusionRadiomic signatures from T2WI and T2WI with DWI may provide added value for pretreatment risk assessment and for guiding tailored treatment strategies in CC.

Project description:ObjectiveTo investigate the potential association among preoperative breast MRI features, axillary nodal burden (ANB), and disease-free survival (DFS) in patients with early-stage breast cancer.Materials and methodsWe retrospectively reviewed 297 patients with early-stage breast cancer (cT1-2N0M0) who underwent preoperative MRI between December 2016 and December 2018. Based on the number of positive axillary lymph nodes (LNs) determined by postoperative pathology, the patients were divided into high nodal burden (HNB; ≥3 positive LNs) and non-HNB (<3 positive LNs) groups. Univariable and multivariable logistic regression analyses were performed to identify independent risk factors associated with ANB. Predictive efficacy was evaluated using the receiver operating characteristic (ROC) curve and area under the curve (AUC). Univariable and multivariable Cox proportional hazards regression analyses were performed to determine preoperative features associated with DFS.ResultsWe included 47 and 250 patients in the HNB and non-HNB groups, respectively. Multivariable logistic regression analysis revealed that multifocality/multicentricity (adjusted odds ratio [OR] = 3.905, 95% confidence interval [CI]: 1.685-9.051, P = 0.001) and peritumoral edema (adjusted OR = 3.734, 95% CI: 1.644-8.479, P = 0.002) were independent risk factors for HNB. Combined peritumoral edema and multifocality/multicentricity achieved an AUC of 0.760 (95% CI: 0.707-0.807) for predicting HNB, with a sensitivity and specificity of 83.0% and 63.2%, respectively. During the median follow-up period of 45 months (range, 5-61 months), 26 cases (8.75%) of breast cancer recurrence were observed. Multivariable Cox proportional hazards regression analysis indicated that younger age (adjusted hazard ratio [HR] = 3.166, 95% CI: 1.200-8.352, P = 0.021), larger tumor size (adjusted HR = 4.370, 95% CI: 1.671-11.428, P = 0.002), and multifocality/multicentricity (adjusted HR = 5.059, 95% CI: 2.166-11.818, P < 0.001) were independently associated with DFS.ConclusionPreoperative breast MRI features may be associated with ANB and DFS in patients with early-stage breast cancer.

Project description:BACKGROUND:Minimally invasive surgery was adopted as an alternative to laparotomy (open surgery) for radical hysterectomy in patients with early-stage cervical cancer before high-quality evidence regarding its effect on survival was available. We sought to determine the effect of minimally invasive surgery on all-cause mortality among women undergoing radical hysterectomy for cervical cancer. METHODS:We performed a cohort study involving women who underwent radical hysterectomy for stage IA2 or IB1 cervical cancer during the 2010-2013 period at Commission on Cancer-accredited hospitals in the United States. The study used inverse probability of treatment propensity-score weighting. We also conducted an interrupted time-series analysis involving women who underwent radical hysterectomy for cervical cancer during the 2000-2010 period, using the Surveillance, Epidemiology, and End Results program database. RESULTS:In the primary analysis, 1225 of 2461 women (49.8%) underwent minimally invasive surgery. Women treated with minimally invasive surgery were more often white, privately insured, and from ZIP Codes with higher socioeconomic status, had smaller, lower-grade tumors, and were more likely to have received a diagnosis later in the study period than women who underwent open surgery. Over a median follow-up of 45 months, the 4-year mortality was 9.1% among women who underwent minimally invasive surgery and 5.3% among those who underwent open surgery (hazard ratio, 1.65; 95% confidence interval [CI], 1.22 to 2.22; P=0.002 by the log-rank test). Before the adoption of minimally invasive radical hysterectomy (i.e., in the 2000-2006 period), the 4-year relative survival rate among women who underwent radical hysterectomy for cervical cancer remained stable (annual percentage change, 0.3%; 95% CI, -0.1 to 0.6). The adoption of minimally invasive surgery coincided with a decline in the 4-year relative survival rate of 0.8% (95% CI, 0.3 to 1.4) per year after 2006 (P=0.01 for change of trend). CONCLUSIONS:In an epidemiologic study, minimally invasive radical hysterectomy was associated with shorter overall survival than open surgery among women with stage IA2 or IB1 cervical carcinoma. (Funded by the National Cancer Institute and others.).

Project description:ObjectiveTo identify predictors of ovarian conservation at hysterectomy and to examine the association of ovarian conservation and survival of young women with early-stage cervical cancer.MethodsThis is a retrospective cohort study using the Surveillance, Epidemiology, and End Results Program to identify hysterectomy-based surgically treated patients with stage I cervical cancer diagnosed between 1983 and 2012 (N=16,511). Multivariable models were used to identify independent factors associated with ovarian conservation. Among the subgroup of 9,419 women younger than 50 years of age with stage I disease, survival outcomes and causes of death were examined for 3,908 (41.5%) women who underwent ovarian conservation at hysterectomy without radiotherapy.ResultsOn multivariable analysis, age younger than 50 years, stage IA disease, and squamous histology were independent factors associated with ovarian conservation (all, P<.001). Among 5,526 women younger than 50 years of age with stage IA disease who underwent hysterectomy without radiotherapy, overall survival was significantly higher in patients undergoing ovarian conservation than in those undergoing oophorectomy (20-year rate, 93.5% compared with 86.8%, P<.001); cervical cancer-specific survival was similar between the patients who underwent ovarian conservation and those who underwent oophorectomy (98.8% compared with 97.8%, P=.12). On multivariable analysis, ovarian conservation remained an independent prognostic factor for improved overall survival (adjusted hazard ratio 0.63, 95% confidence interval [CI] 0.49-0.82, P=.001) and was independently associated with lower cumulative risks of death resulting from cardiovascular disease (20-year cumulative rate, 1.2% compared with 3.3%, adjusted hazard ratio 0.47, 95% CI 0.26-0.86, P=.014) and other chronic disease (0.5% compared with 1.4%, adjusted hazard ratio 0.24, 95% CI 0.09-0.65, P=.005) compared with oophorectomy. Both cervical cancer-specific survival (20-year rate, 93.1% compared with 92.0%, P=.37) and overall survival (86.7% compared with 84.6%, P=.12) were similar between ovarian conservation and oophorectomy among 3,893 women younger than 50 years of age with stage IB disease who underwent hysterectomy without radiotherapy.ConclusionAmong young women with stage IA cervical cancer, ovarian conservation at hysterectomy is associated with decreased all-cause mortality including death resulting from cardiovascular disease and other chronic diseases.

Project description:GINS complex subunit 2 (GINS2), a member of the GINS complex, is involved in DNA replication. GINS2 is upregulated in a variety of aggressive tumors. However, its role in cervical cancer carcinogenesis remains to be elucidated. We investigated the clinical significance of GINS2 in patients with early-stage cervical cancer and its biological functions in cervical cancer progression. GINS2 expression was analyzed in cervical cancer cell lines and in 8 matched cervical cancer samples at the mRNA and protein levels using real-time PCR and western blotting, respectively. GINS2 protein expression in 155 paraffin-embedded cervical cancer specimens was validated using immunohistochemistry. Statistical analysis was used to evaluate its clinicopathological significance. Short hairpin RNA interference, anchorage-independent growth ability, colony formation assay, wound healing ability, Transwell assays and western blotting were used to determine the effects of GINS2 on the aggressive phenotype of cervical cancer cells. There was obvious upregulation of GINS2 in the cervical cancer cell lines and tumor specimens compared to that in the normal cervical tissues. Significant correlations were identified between GINS2 expression and squamous cell carcinoma antigen (SCC-Ag; P<0.001), deep stromal invasion (P=0.021), vital status (P<0.001), recurrence (P<0.001) and pelvic lymph node metastasis (PLNM; P<0.001). Moreover, patients with higher GINS2 expression had shorter overall survival (OS) compared to patients with low GINS2 expression. Multivariate analysis revealed that GINS2 may serve as an independent risk factor of poor prognosis in early-stage cervical cancer. In addition, GINS2 downregulation markedly suppressed cell proliferation and tumorigenic ability, as well as cell migration and invasion. Our findings suggest that GINS2 is a novel indicator of PLNM and a valuable prognostic biomarker in early-stage cervical cancer, and subsequently is a valuable molecular target for cervical cancer diagnosis and treatment.

Project description:PurposeTo identify radiomic features extracted from the tumor habitat on routine MR images that are prognostic for progression-free survival (PFS) and to assess their morphologic basis with corresponding histopathologic attributes in glioblastoma (GBM).Materials and methodsIn this retrospective study, 156 pretreatment GBM MR images (gadolinium-enhanced T1-weighted, T2-weighted, and fluid-attenuated inversion recovery [FLAIR] images) were curated. Of these 156 images, 122 were used for training (90 from The Cancer Imaging Archive and 32 from the Cleveland Clinic, acquired between December 1, 2011, and May 1, 2018) and 34 were used for validation. The validation set was obtained from the Ivy Glioblastoma Atlas Project database, for which the percentage extent of 11 histologic attributes was available on corresponding histopathologic specimens of the resected tumor. Following expert annotations of the tumor habitat (necrotic core, enhancing tumor, and FLAIR-hyperintense subcompartments), 1008 radiomic descriptors (eg, Haralick texture features, Laws energy features, co-occurrence of local anisotropic gradient orientations [CoLIAGe]) were extracted from the three MRI sequences. The top radiomic features were obtained from each subcompartment in the training set on the basis of their ability to risk-stratify patients according to PFS. These features were then concatenated to create a radiomics risk score (RRS). The RRS was independently validated on a holdout set. In addition, correlations (P < .05) of RRS features were computed, with the percentage extent of the 11 histopathologic attributes, using Spearman correlation analysis.ResultsRRS yielded a concordance index of 0.80 on the validation set and constituted radiomic features, including Laws (capture edges, waves, ripple patterns) and CoLIAGe (capture disease heterogeneity) from enhancing tumor and FLAIR hyperintensity. These radiomic features were correlated with histopathologic attributes associated with disease aggressiveness in GBM, particularly tumor infiltration (P = .0044) and hyperplastic blood vessels (P = .0005).ConclusionPreliminary findings demonstrated significant associations of prognostic radiomic features with disease-specific histologic attributes, with implications for risk-stratifying patients with GBM for personalized treatment decisions. Supplemental material is available for this article. © RSNA, 2020.

Dataset Information

Association of MRI-derived radiomic biomarker with disease-free survival in patients with early-stage cervical cancer.

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Association of MRI-derived radiomic biomarker with disease-free survival in patients with early-stage cervical cancer.

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