Pairwise machine learning-based automatic diagnostic platform utilizing CT images and clinical information for predicting radiotherapy locoregional recurrence in elderly esophageal cancer patients.

OBJECTIVE: To investigate the feasibility and accuracy of predicting locoregional recurrence (LR) in elderly patients with esophageal squamous cell cancer (ESCC) who underwent radical radiotherapy using a pairwise machine learning algorithm. METHODS: The 130 datasets enrolled were randomly divided into a training set and a testing set in a 7:3 ratio. Clinical factors were included and radiomics features were extracted from pretreatment CT scans using pyradiomics-based software, and a pairwise naive Bayes (NB) model was developed. The performance of the model was evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). To facilitate practical application, we attempted to construct an automated esophageal cancer diagnosis system based on trained models. RESULTS: To the follow-up date, 64 patients (49.23%) had experienced LR. Ten radiomics features and two clinical factors were selected for modeling. The model demonstrated good prediction performance, with area under the ROC curve of 0.903 (0.829-0.958) for the training cohort and 0.944 (0.849-1.000) for the testing cohort. The corresponding accuracies were 0.852 and 0.914, respectively. Calibration curves showed good agreement, and DCA curve confirmed the clinical validity of the model. The model accurately predicted LR in elderly patients, with a positive predictive value of 85.71% for the testing cohort. CONCLUSIONS: The pairwise NB model, based on pre-treatment enhanced chest CT-based radiomics and clinical factors, can accurately predict LR in elderly patients with ESCC. The esophageal cancer automated diagnostic system embedded with the pairwise NB model holds significant potential for application in clinical practice.

Computed tomography radiomics identification of T1-2 and T3-4 stages of esophageal squamous cell carcinoma: two-dimensional or three-dimensional?

BACKGROUND: To evaluate two-dimensional (2D) and three-dimensional (3D) computed tomography (CT) radiomics analysis for the T stage of esophageal squamous cell carcinoma (ESCC). METHODS: 398 patients with pathologically confirmed ESCC were divided into training and testing sets. All patients underwent chest CT scans preoperatively. For each tumor, based on CT images, a 2D region of interest (ROI) was outlined on the largest cross-sectional area, and a 3D ROI was outlined layer by layer on each section of the tumor. The radiomics platform was used for feature extraction. For feature selection, stepwise logistic regression was used. The receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of the 2D radiomics model versus the 3D radiomics model. The differences were compared using the DeLong test. The value of the clinical utility of the two radiomics models was evaluated. RESULTS: 1595 radiomics features were extracted. After screening, two radiomics models were constructed. In the training set, the difference between the area under the curve (AUC) of the 2D radiomics model (AUC = 0.831) and the 3D radiomics model (AUC = 0.830) was not statistically significant (p = 0.973). In the testing set, the difference between the AUC of the 2D radiomics model (AUC = 0.807) and the 3D radiomics model (AUC = 0.797) was also not statistically significant (p = 0.748). A 2D model was equally useful as a 3D model in clinical situations. CONCLUSION: The performance of 2D radiomics model is comparable to that of 3D radiomics model in distinguishing between the T1-2 and T3-4 stages of ESCC. In addition, 2D radiomics model may be a more feasible option due to the shorter time required for segmenting the ROI.

Comparison of TNM AJCC/UICC 8th with JES 11th staging systems for prognostic prediction in patients with esophageal squamous cell carcinoma who underwent radical (chemo) radiotherapy in China.

OBJECTIVE: The aim of the study was to compare the prognostic prediction performances of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 8th staging system and the Japan Esophageal Society (JES) 11th staging system for patients with esophageal squamous cell carcinoma who underwent radical (chemo) radiotherapy. METHODS: In total, 574 patients were enrolled and categorized according to the tumor, node metastasis (TNM) AJCC/UICC 8th and JES 11th editions. Survival rates and disease-free survival were computed using the Kaplan-Meier technique. The log-rank test was used for survival difference analysis. RESULTS: (1) The 8th AJCC/UICC N staging exhibited significant stratification for overall survival (OS) and progression-free survival (PFS). JES 11th showed significant OS stratification, but PFS was not well-stratified for N2-N4. (2) Both staging systems demonstrated significant stratification for OS and PFS. (3) AJCC/UICC 8th TNM staging yielded significantly well-stratified OS and PFS in the differing staging group. JES 11th failed to stratify OS and PFS for stages III and IVA. (4) AJCC/UICC 8th TNM stratified OS and PFS significantly well for lower and middle region tumors, whereas JES 11th inadequately stratified stages III and IVA. (5) Significant multivariable analysis results indicated that AJCC/UICC 8th independently predicted poor OS and PFS. CONCLUSIONS: In Chinese patients with esophageal squamous cell carcinoma who underwent radical (chemo) radiotherapy, the AJCC/UICC 8th edition exhibited superior prognostic prediction capabilities compared with the JES 11th edition.

Can lymphovascular invasion be predicted by contrast-enhanced CT imaging features in patients with esophageal squamous cell carcinoma? A preliminary retrospective study.

BACKGROUND: To investigate the value of contrast-enhanced CT (CECT)-derived imaging features in predicting lymphovascular invasion (LVI) status in esophageal squamous cell carcinoma (ESCC) patients. METHODS: One hundred and ninety-seven patients with postoperative pathologically confirmed esophageal squamous cell carcinoma treated in our hospital between January 2017 and January 2019 were enrolled in our study, including fifty-nine patients with LVI and one hundred and thirty-eight patients without LVI. The CECT-derived imaging features of all patients were analyzed. The CECT-derived imaging features were divided into quantitative features and qualitative features. The quantitative features consisted of the CT attenuation value of the tumor (CTVTumor), the CT attenuation value of the normal esophageal wall (CTVNormal), the CT attenuation value ratio of the tumor-to-normal esophageal wall (TNR), the CT attenuation value difference between the tumor and normal esophageal wall (ΔTN), the maximum thickness of the tumor measured by CECT (Thickness), the maximum length of the tumor measured by CECT (Length), and the gross tumor volume measured by CECT (GTV). The qualitative features consisted of an enhancement pattern, tumor margin, enlarged blood supply or drainage vessels to the tumor (EVFDT), and tumor necrosis. For the clinicopathological characteristics and CECT-derived imaging feature analysis, the chi-squared test was used for categorical variables, the Mann-Whitney U test was used for continuous variables with a nonnormal distribution, and the independent sample t-test was used for the continuous variables with a normal distribution. The trend test was used for ordinal variables. The association between LVI status and CECT-derived imaging features was analyzed by univariable logistic analysis, followed by multivariable logistic regression and receiver operating characteristic (ROC) curve analysis. RESULTS: The CTVTumor, TNR, ΔTN, Thickness, Length, and GTV in the group with LVI were higher than those in the group without LVI (P < 0.05). A higher proportion of patients with heterogeneous enhancement pattern, irregular tumor margin, EVFDT, and tumor necrosis were present in the group with LVI (P < 0.05). As revealed by the univariable logistic analysis, the CECT-derived imaging features, including CTVTumor, TNR, ΔTN and enhancement pattern, Thickness, Length, GTV, tumor margin, EVFDT, and tumor necrosis were associated with LVI status (P < 0.05). Only the TNR (OR 8.655; 95% CI 2.125-37.776), Thickness (OR 6.531; 95% CI 2.410-20.608), and tumor margin (OR 4.384; 95% CI 2.004-9.717) were independent risk factors for LVI in the multivariable logistic regression analysis. The ROC curve analysis incorporating the above three CECT-derived imaging features showed that the area under the curve obtained by the multivariable logistic regression model was 0.820 (95% CI 0.754-0.885). CONCLUSION: The CECT-derived imaging features, including TNR, Thickness, tumor margin, and their combination, can be used as predictors of LVI status for patients with ESCC.

Predicting the effects of radiotherapy based on diffusion kurtosis imaging in a xenograft mouse model of esophageal carcinoma.

The aim of the present study was to assess the predictive value of diffusion kurtosis imaging (DKI) on the effects of radiotherapy in a xenograft model of esophageal cancer. A total of 40 tumor-bearing mice, established by injection of Eca-109 cells in nude mice, were used. The experimental group (n=24) received a single dose of 15 Gy (6 MV by X-ray), and the control group (n=16) did not receive any treatment. Tumor volume, apparent diffusion coefficient (ADC), mean kurtosis (MK) and mean diffusivity (MD) of the two groups were compared, and the expression of aquaporin (AQP) 3 and necrosis ratio at matched time points in xenografts were also observed. There was a significant difference between the two groups from the 7th day of radiotherapy onwards; the xenograft volume of the experimental group was significantly smaller compared with the control group (P<0.05). On the 3rd day, the ADC and MD of the experimental group was significantly higher compared with the control group, and MK was significantly lower compared with the control group (P<0.05). On the 3rd day, AQP3 expression in the experimental group was lower compared with the control group, and the proportion of necrotic cells was higher compared with the control group (P<0.05). Single large fraction dose radiotherapy inhibited the growth of a xenografted esophageal tumor. Changes in ADC, MK and MD were observed prior to morphological changes in the tumor. The change in AQP3 expression and necrosis ratio was in also agreement with the DKI parameters assessed. DKI may thus provide early predictive ability on the effect of radiotherapy in esophageal carcinoma.

Prediction of radiotherapy effect by diffusion-weighted imaging in esophageal carcinoma xenograft model.

AIM: This study was to evaluate the value of diffusion-weighted imaging (DWI) in predicting the efficacy of radiotherapy for esophageal cancer from xenograft model level. SUBJECTS AND METHODS: Thirty-two tumor-bearing mice from the Eca-109 cell line nude mice models were established. The experimental group (n = 16) received a single dose of 15 Gy (6MV X-ray), whereas the control group (n = 16) did not receive any treatment. The tumor volume and apparent diffusion coefficient (ADC) were obtained. The cell density, tissue necrosis ratio, and CD31 expression were determined at matched time points. RESULTS: The tumor volume was smaller in the experimental group than in the control group (P < 0.05) on the 7th day after radiotherapy (1.580 ± 0.965 cm3 vs. 2.671 ± 0.915 cm3). The ADC values were higher in the experimental group than in the control group on the 3rd day (P < 0.05) (998.15 ± 163.76 ×10- 6 mm2/s vs. 833.32 ± 142.15 ×10- 6 mm2/s). On the 3rd day after radiotherapy, the differences in cell density and necrosis ratio between the two groups were statistically significant; the tumor cell density was lower in the experimental group (25.56 ± 1.40%) than in the control group (33.48 ± 4.18%) (P < 0.05), and the proportion of tissue necrosis was higher in the experimental group (32.19 ± 1.21%) than in the control group (29.16 ± 2.16%) (P < 0.05). The negative and weak positive rate of CD31 expression in the experimental group was higher than the control group, whereas the generally positive and strong positive rate of CD31 expression was significantly lower than the control group in the early stage (P < 0.05). CONCLUSION: ADC values may change at the early stage before the morphological changes of tumors. Changes in cell density and necrosis ratio of transplanted tumors correspond to the changes in ADC values. DWI can be used for the early prediction of esophageal cancer radiotherapy efficacy.

Survival Comparision of Three-dimensional Radiotherapy Alone vs. Chemoradiotherapy for Esophageal Squamous Cell Carcinoma.

BACKGROUND AND OBJECTIVE: To compare the survival of esophageal squamous cell carcinoma (ESCC) patients who received chemoradiotherapy (CRT) or radiotherapy (RT) alone. METHODS: A total of 753 well-matched patients were enrolled. A total of 299 patients were treated with CRT, and 454 patients were treated with RT alone. Propensity score matching (PSM) was performed with the R project. The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used to assess differences in survival. RESULTS: The response rate was 99.0% with CRT and 98.3% with RT alone (p = 0.651). The 1-, 3-, 5- and 10 year overall survival (OS) rates were as follows: 72.2, 40.1, 30.7 and 13.9% with CRT, 68.1, 35.2%, 23.3 and 12.5% with RT alone (p = 0.033); 73.4, 40.1, 31.0 and 16.1% with concurrent chemoradiotherapy (CCRT); and 68.1, 35.2, 23.3 and 12.5% with RT alone (p = 0.028). There was no significant difference in OS between the CCRT group and the sequential chemoradiotherapy (SCRT) group (p = 0.527). Consolidation chemotherapy (CCT) after CCRT led to a significant increase in the OS rate compared with no CCT after CCRT (p = 0.003). Compared with the OS of patients who received 1∼2 cycles of CCT, the OS of patients who received 3∼4 cycles of CCT was significantly improved (p = 0.011). Acute toxic effects were more severe in the CRT, but no significant differences in late reactions. CRT exhibited more appetite loss and fatigue symptoms than RT alone, and dysphagia of CRT relief more obviously. The CRT group had a significantly lower rate of local control failure than the RT alone group (p = 0.019). CONCLUSIONS: For patients with ESCC, CRT led to a significantly improved OS compared to RT alone, and this trend was more obvious with CCRT. CCT after CCRT prolonged OS, especially in patients who received at least 2 cycles of CCT. CRT can reduce the deaths due to local control failure compared to RT alone.

Relationship between WBRT total dose, intracranial tumor control, and overall survival in NSCLC patients with brain metastases - a single-center retrospective analysis.

BACKGROUND: The relationship between whole brain radiotherapy (WBRT) dose with intracranial tumor control and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) brain metastases (BM) is largely unknown. METHODS: We retrospectively analyzed 595 NSCLC BM patients treated consecutively at the Fourth Hospital of Hebei Medical University between 2013 to 2015. We assigned the patients into 4 dose groups of WBRT: none, < 30, 30-39, and ≥ 40 Gy and assessed their relationship with OS and intracranial progression-free survival (iPFS). Cox models were utilized. Covariates included sex, age, KPS, BM lesions, extracranial metastasis, BM and lung tumor resection, chemotherapy, targeted therapy, and focal radiotherapy modalities. RESULTS: Patients had a mean age of 59 years and were 44% female. Their median survival time (MST) of OS and iPFS were 9.3 and 8.9 months. Patients receiving none (344/58%), < 30 (30/5%), 30-39 (93/16%), and ≥ 40 (128/22%) Gy of WBRT had MST of OS (iPFS) of 7.3 (6.8), 6.0 (5.4), 10.3 (11.9) and 11.9 (11.9) months, respectively. Compared to none, other WBRT groups had adjusted HRs for OS - 1.23 (p > 0.20), 0.72 (0.08), 0.61 (< 0.00) and iPFS - 1.63 (0.03), 0.71 (0.06), 0.67 (< 0.01). Compared to 30-39 Gy, WBRT dose ≥40 Gy was not associated with improved OS and iPFS (all p > 0.40). Stratified analyses by 1-3 and ≥ 4 BM lesions and adjustment analyses by each prognostic index of RPA class, Lung-GPA and Lung-molGPA supported these relationships as well. CONCLUSIONS: Compared to none, WBRT doses ≥30 Gy are invariably associated with improved intracranial tumor control and survival in NSCLC BM patients.

Investigation of using diffusion-weighted magnetic resonance imaging to evaluate the therapeutic effect of esophageal carcinoma treatment.

AIM: To explore the associations of diffusion-weighted magnetic resonance imaging (DWI) measurements with the therapeutic effect (TE) on and survival of esophageal carcinoma patients treated with chemoradiotherapy (CRT). METHODS: From March 2010 to December 2011, 77 patients were prospectively enrolled into a cohort study. DWI was performed at the beginning and 1-3 months after CRT. The immediate post-CRT TE was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST). The associations between the disappearance status of hyperintense expression (HE) in DWI and the apparent diffusion coefficient (ADC) of DWI with the complete response (CR) as TE and survival were analyzed. RESULTS: 3 patients were excluded due to the absence of HE in DWI. Analysis of the remaining 74 patients indicated that their ADC values were significantly improved from 1.64 ± 0.48 to 2.65 ± 0.58 mm2/s from pre-CRT to post-CRT (p = 0.000). Both univariate and multivariate Cox model analyses showed that high post-CRT ADC values and the disappearance status of HE associated significantly with the TE (CR rate) and survival. CONCLUSIONS: DWI examination could afford useful markers to predict the treatment response as well as the survival of patients with esophageal squamous cell carcinoma. The non-disappearance of HE in DWI and low ADC values after CRT were risk factors.