Nimotuzumab plus concurrent chemo-radiotherapy in unresectable locally advanced oesophageal squamous cell carcinoma (ESCC): interim analysis from a Phase 3 clinical trial.

BACKGROUND: This prospectively randomised, double-blinded, placebo-controlled, multicenter Phase 3 clinical trial was conducted to assess the efficacy and safety profile of nimotuzumab (nimo) plus concurrent chemo-radiotherapy (CCRT) in patients with unresectable locally advanced ESCC. METHODS: Patients were randomly assigned (1:1) to receive CCRT plus nimotuzumab or placebo. The primary endpoint was overall survival (OS). In addition, interim analysis for short-term response rate was pre-defined. RESULTS: A total of 201 patients were randomised into two groups. Eighty patients in the nimo group and eighty-two in the placebo group were evaluable. Three to six months after treatment, 26 (32.5%) patients achieved complete response (CR) in the nimo group, and 10 (12.2%) in the placebo group (P = 0.002). The ORR of the nimo group was significantly higher than the placebo group (93.8% vs. 72.0%, P < 0.001). The two groups' grade 3-5 adverse drug reactions were 11.1% vs. 10.9% (P > 0.05). CONCLUSIONS: Nimotuzumab, in combination with chemo-radiotherapy, increased the CRR and ORR with a good safety profile. The OS is needed to be followed and finally analysed. CLINICAL TRIAL REGISTRATION: NCT02409186.

A novel nomogram containing acute radiation esophagitis predicting radiation pneumonitis in thoracic cancer receiving radiotherapy.

BACKGROUND: Radiation-induced pneumonitis (RP) is a non-negligible and sometimes life-threatening complication among patients with thoracic radiation. We initially aimed to ascertain the predictive value of acute radiation-induced esophagitis (SARE, grade ≥ 2) to symptomatic RP (SRP, grade ≥ 2) among thoracic cancer patients receiving radiotherapy. Based on that, we established a novel nomogram model to provide individualized risk assessment for SRP. METHODS: Thoracic cancer patients who were treated with thoracic radiation from Jan 2018 to Jan 2019 in Shandong Cancer Hospital and Institute were enrolled prospectively. All patients were followed up during and after radiotherapy (RT) to observe the development of esophagitis as well as pneumonitis. Variables were analyzed by univariate and multivariate analysis using the logistic regression model, and a nomogram model was established to predict SRP by "R" version 3.6.0. RESULTS: A total of 123 patients were enrolled (64 esophageal cancer, 57 lung cancer and 2 mediastinal cancer) in this study prospectively. RP grades of 0, 1, 2, 3, 4 and 5 occurred in 29, 57, 31, 0, 3 and 3 patients, respectively. SRP appeared in 37 patients (30.1%). In univariate analysis, SARE was shown to be a significant predictive factor for SRP (P < 0.001), with the sensitivity 91.9% and the negative predictive value 93.5%. The incidence of SRP in different grades of ARE were as follows: Grade 0-1: 6.5%; Grade 2: 36.9%; Grade 3: 80.0%; Grade 4: 100%. Besides that, the dosimetric factors considering total lung mean dose, total lung V5, V20, ipsilateral lung mean dose, ipsilateral lung V5, and mean esophagus dose were correlated with SRP (all P < 0.05) by univariate analysis. The incidence of SRP was significantly higher in patients whose symptoms of RP appeared early. SARE, mean esophagus dose and ipsilateral mean lung dose were still significant in multivariate analysis, and they were included to build a predictive nomogram model for SRP. CONCLUSIONS: As an early index that can reflect the tissue's radiosensitivity visually, SARE can be used as a predictor for SRP in patients receiving thoracic radiation. And the nomogram containing SARE may be fully applied in future's clinical work.

Local therapy combined with chemotherapy versus chemotherapy for postoperative oligometastatic non-small-cell lung cancer.

Aim: To compare the efficacy and toxicity of local therapy plus chemotherapy versus chemotherapy in non-small-cell lung cancer (NSCLC) patients with oligometastases after surgery. Patients & methods: A total of 152 patients with oligometastases after surgery were enrolled. Data of patient survival, treatment response and toxicities were compared between the groups receiving local ablative therapy plus chemotherapy and chemotherapy alone. Results: Compared with chemotherapy, the combination treatment conferred better progression-free survival, objective response rate and disease control rate (10 vs 7 months; 66.7 vs 31.9%; 94.3 vs 80.9%, respectively), but with more grade ≥3 adverse events. Besides, the overall survival was not significantly different (19 vs 20 months). Conclusion: The addition of local therapy to chemotherapy improved progression-free survival, objective response rate and disease control rate, but not overall survival in postoperative oligometastatic non-small-cell lung cancer.

Prognostic value of dynamic albumin-to-alkaline phosphatase ratio in limited stage small-cell lung cancer.

AIM: To dynamically investigate the prognostic value of albumin-to-alkaline phosphatase ratio (AAPR) in limited stage small-cell lung cancer. MATERIALS & METHODS:  The AAPR within 1 week before and after chemoradiation therapy (pre- and post-AAPR) was collected and analyzed. RESULTS: Patients with low pre- or post-AAPR had shorter overall survival and progression-free survival than the high groups (p-values all <0.05). Post-AAPR was an independent prognostic factor for progression-free survival (p = 0.007) and overall survival (p = 0.003). The integration of pre- or post-AAPR improved the prognostic ability of Tumor, Node, Metastasis stage alone (0.55-0.64 and 0.68, respectively). CONCLUSION:  Post-AAPR is a reliable prognostic factor for limited stage small-cell lung cancer patients. The complementary value of AAPR to Tumor, Node, Metastasis stage is worth further validation in the future.

Effect of celecoxib on inhibiting tumor repopulation during radiotherapy in human FaDu squamous cell carcinoma.

AIM OF THE STUDY: FaDu human squamous cell carcinoma (FaDu-hSCC) demonstrated accelerated tumor repopulation during fractionated irradiation with pathological validation in a xenograft model system. Previous studies showed that the selective cyclooxygenase (COX)-2 inhibitor celecoxib can enhance the tumor response to radiotherapy. So we aimed to explore the effect of celecoxib in inducing apoptosis and inhibiting repopulation of FaDu tumors in nude mice during fractionated radiotherapy. MATERIAL AND METHODS: FaDu-hSCC was transplanted into the right hind leg of BALB/C nude mice. Mice were treated with celecoxib and/or fractionated irradiation. Celecoxib (100 mg/kg/day) was administered by daily gavage. Irradiation was delivered with 12 to 18 fractions of 3.0 Gy daily or every second day based on Petersen's repopulation model. At different time points, tumors were excised for immunohistochemistry staining. RESULTS: Significant tumor repopulation occurred after about 18 days of radiotherapy. On average, Ki-67 and bromodeoxyuridine (BrdUrd) labeling indices (LI) decreased with daily irradiation (both p < 0.05) and increased with every-second-day irradiation (both p > 0.05), suggesting accelerated repopulation. Ki-67 LI decreased in celecoxib concurrent with radiotherapy for 12 fractions in 24 days and 18 fractions in 36 days compared with irradiated alone (p = 0.004 and 0.042, respectively). BrdUrd LI values were lower in the concurrent groups than irradiated alone (p = 0.001 and 0.006, respectively). Epithelial growth factor receptor (EGFR) expression score decreased in the concurrent groups than irradiated alone (p = 0.037 and 0.031, respectively). Caspase-3 expression scores were higher in the concurrent groups than irradiated alone (p = 0.05 and 0.006, respectively). CONCLUSIONS: Celecoxib concurrent radiotherapy could inhibit tumor repopulation and increase tumor apoptosis during the treatment in FaDu squamous cell carcinoma.

DIRECT-Net: A unified mutual-domain material decomposition network for quantitative dual-energy CT imaging.

PURPOSE: The purpose of this paper is to present an end-to-end deep convolutional neural network to improve the dual-energy CT (DECT) material decomposition performance. METHODS: In this study, we proposes a unified mutual-domain (sinogram domain and CT domain) material decomposition network (DIRECT-Net) for DECT imaging. By design, the DIRECT-Net has immediate access to mutual-domain data, and utilizes stacked convolution neural network layers for noise reduction and material decomposition. The training data are numerically generated following the fundamental DECT imaging physics. Numerical simulation of the XCAT digital phantom, experiments of a biological specimen, a calcium chloride phantom and an iodine solution phantom are carried out to evaluate the performance of DIRECT-Net. Comparisons are performed with different DECT decomposition algorithms. RESULTS: Results demonstrate that the proposed DIRECT-Net can generate water and bone basis images with less artifacts compared to the other decomposition methods. Additionally, the quantification errors of the calcium chloride (75-375 mg/cm3 ) and the iodine (2-20 mg/cm3 ) are less than 4%. CONCLUSIONS: An end-to-end material decomposition network is proposed for quantitative DECT imaging. The qualitative and quantitative results demonstrate that this new DIRECT-Net has promising benefits in improving the DECT image quality.

[Prognostic value of CYFRA 21-1 and CEA in patients with undifferentiated nasopharyngeal carcinoma before and after radiotherapy].

OBJECTIVE: The purpose of this study was to evaluate the potential of CYFRA 21-1 (CYFRA) and CEA as a prognostic marker in patients with undifferentiated nasopharyngeal carcinoma (NPC). METHODS: From March 2004 to February 2008, 62 patients with newly diagnosed, undifferentiated NPC were treated in our department. Their clinocopathological data were analyzed retrospectively. All patients received intensity-modulated radiotherapy using 6 MV X-rays, and serum CYFRA and CEA before and after radiotherapy were assayed. The association among the long-term follow-up results and age, sex, smoke, TNM stage, chemotherapy, CEA, CYFRA and the changes in any direction of serum CYFRA and CEA were determined. RESULTS: Patients with low pre-RT level (≤ 2.49 µg/L) of CYFRA had a significantly better overall survival (OS) than patients with high level (> 2.49 µg/L,OR = 8.555, P = 0.029). N classification and T classification were positively associated with the prediction of progression free survival (OR = 4.054, P = 0.001;OR = 3.873, P = 0.001). But there was no significant association between the rest predictors (age, sex, CEA, post-RT CYFRA, chemotherapy and a radiation-induced decrease in serum markers) and the survival or recurrence rate by multivariate analysis. CONCLUSIONS: The results of the present study show that pre-RT serum CYFRA level is a valuable factor for predicting long-term survival in patients with undifferentiated nasopharyngeal carcinoma. More aggressive treatment may be given to those patients with a high serum CYFRA level.

Toxicity Profile of Combining PD-1/PD-L1 Inhibitors and Thoracic Radiotherapy in Non-Small Cell Lung Cancer: A Systematic Review.

Background: The combination of immune checkpoint inhibitors (ICIs) and thoracic radiotherapy (TRT) has shown significant clinical activity in patients with non-small cell lung cancer (NSCLC). However, the currently available data on adverse events (AEs) were derived from a small subset of patients included in prospective clinical trials or retrospective studies. Thus, we conducted this systematic review to determine the AEs associated with this combination treatment. Methods: An electronic literature search was performed in databases and conference proceedings of prospective clinical trials assessing the combination of ICIs and TRT for patients with NSCLC. The systematic analysis was conducted to determine the profile and incidence of AEs of combination treatment. We further performed the comparison of AEs between programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, and sequential and concurrent administration of ICIs and TRT to help identify high risk patients. The systematic analyses were conducted with the Review Manager (version 5.3; The Cochrane Collaboration, Oxford, United Kingdom) and Stata version 12.0 (StataCorp, College Station, TX, USA) software. Results: Eleven clinical trials involving 1,113 patients with NSCLC were eligible for analysis. The incidence of all-grade AEs was 95.5%; that of high-grade AEs (grade ≥3) was 30.2%. The most frequent all-grade AE was fatigue (49.7%), while pneumonitis was the most common high-grade AE (3.8%) and grade 5 AE (0.6%). Notably, the toxicity profiles of PD-1 and PD-L1 inhibitors were similar. Concurrent treatment was associated with a higher incidence of higher-grade AEs (41.6% vs 24.8%, P=0.17) and pneumonitis (7.1% vs 3.9%, P=0.14) compared to sequential treatment, but no significant difference was observed. Conclusion: Most AEs of this combination treatment are tolerable; as the most common high-grade AE, pneumonitis deserves the utmost attention of physicians. The toxicity profiles of patients receiving PD-1 or PD-L1 were similar, and no significant difference was observed between concurrent and sequential treatment.

Integrating Clinical Data and Attentional CT Imaging Features for Esophageal Fistula Prediction in Esophageal Cancer.

BACKGROUND AND PURPOSE: This study aims to develop a risk model to predict esophageal fistula in esophageal cancer (EC) patients by learning from both clinical data and computerized tomography (CT) radiomic features. MATERIALS AND METHODS: In this retrospective study, computerized tomography (CT) images and clinical data of 186 esophageal fistula patients and 372 controls (1:2 matched by the diagnosis time of EC, sex, marriage, and race) were collected. All patients had esophageal cancer and did not receive esophageal surgery. 70% patients were assigned into training set randomly and 30% into validation set. We firstly use a novel attentional convolutional neural network for radiographic descriptor extraction from nine views of planes of contextual CT, segmented tumor and neighboring structures. Then clinical factors including general, diagnostic, pathologic, therapeutic and hematological parameters are fed into neural network for high-level latent representation. The radiographic descriptors and latent clinical factor representations are finally associated by a fully connected layer for patient level risk prediction using SoftMax classifier. RESULTS: 512 deep radiographic features and 32 clinical features were extracted. The integrative deep learning model achieved C-index of 0.901, sensitivity of 0.835, and specificity of 0.918 on validation set with superior performance than non-integrative model using CT imaging alone (C-index = 0.857) or clinical data alone (C-index = 0.780). CONCLUSION: The integration of radiomic descriptors from CT and clinical data significantly improved the esophageal fistula prediction. We suggest that this model has the potential to support individualized stratification and treatment planning for EC patients.

Eleven routine clinical features predict COVID-19 severity uncovered by machine learning of longitudinal measurements.

Severity prediction of COVID-19 remains one of the major clinical challenges for the ongoing pandemic. Here, we have recruited a 144 COVID-19 patient cohort, resulting in a data matrix containing 3,065 readings for 124 types of measurements over 52 days. A machine learning model was established to predict the disease progression based on the cohort consisting of training, validation, and internal test sets. A panel of eleven routine clinical factors constructed a classifier for COVID-19 severity prediction, achieving accuracy of over 98% in the discovery set. Validation of the model in an independent cohort containing 25 patients achieved accuracy of 80%. The overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 0.70, 0.99, 0.93, and 0.93, respectively. Our model captured predictive dynamics of lactate dehydrogenase (LDH) and creatine kinase (CK) while their levels were in the normal range. This model is accessible at https://www.guomics.com/covidAI/ for research purpose.

Serum CYFRA21-1 as a prognostic marker for patients with undifferentiated nasopharyngeal carcinoma.

The purpose of this study was to evaluate the potential of serum CYFRA21-1 and carcinoembryonic antigen (CEA) as prognostic markers in patients with undifferentiated nasopharyngeal carcinoma. Sixty-one patients who received definitive radiotherapy/chemoradiotherapy were analysed retrospectively. We investigated the association of the follow-up results with pretreatment level, post-treatment level and change of serum CYFRA21-1 and CEA, respectively. Patients with low pretreatment CYFRA21-1 had a significantly better overall survival. There were no significant associations among the remaining serum markers, and the survival and recurrence rates on multivariate analysis. The present study shows that pretreatment CYFRA21-1 level is a potential factor for predicting long-term survival.

Prognostic Value of a Nomogram Based on the Dynamic Albumin-to-Alkaline Phosphatase Ratio for Patients with Extensive-Stage Small-Cell Lung Cancer.

PURPOSE: Small-cell lung cancer (SCLC) is known as the characteristics of high invasion, rapid progression, and poor prognosis. Therefore, identification of patients with high risk of progression and death is critical to improve the survival of patients with extensive-stage SCLC (ES-SCLC). This study was designed to determine the prognostic importance of the albumin-to-alkaline phosphatase ratio (AAPR) in the survival of patients with ES-SCLC and to develop a nomogram based on AAPR dynamics for ES-SCLC prognosis. PATIENTS AND METHODS: Characteristics were reviewed from 300 patients with ES-SCLC. Training and validation cohorts included 200 and 100 patients, respectively. We applied univariate and multivariate Cox models to assess the prognostic value of AAPR for ES-SCLC. The nomogram for progression-free survival (PFS) and overall survival (OS) of ES-SCLC patients was developed based on the multivariate survival analysis of the training cohort. External validation of the established nomogram was performed using the validation cohort. RESULTS: N3 stage, thoracic radiotherapy, and post-AAPR were the independent factors identified for PFS. T stage, thoracic radiotherapy, and high post-AAPR were the independent risk factors identified for death. The prognostic nomogram was established by integrating the independent significant factors for PFS and OS in the training cohort with the c-indices of 0.675 and 0.662, respectively, and validated in the validation cohort. The nomogram had superior prognosis prediction ability than did TNM stage. Decision curve analysis (DCA) also indicated clinical net benefits from the nomogram. CONCLUSION: AAPR was valuable for prognosis prediction in patients with ES-SCLC and was recommended to be dynamically evaluated to guide patient treatment. Additionally, the nomogram covering post-AAPR accurately predicted individual survival probability.

Multiple Immune Features-Based Signature for Predicting Recurrence and Survival of Inoperable LA-NSCLC Patients.

INTRODUCTION: The immune status of the tumor microenvironment is extremely complex. One single immune feature cannot reflect the integral immune status, and its prognostic value was limited. We postulated that the immune signature based on multiple immuno-features could markedly improve the prediction of post-chemoradiotherapeutic survival in inoperable locally advanced non-small-cell lung cancer (LA-NSCLC) patients. METHODS: In this study, 100 patients who were diagnosed as having inoperable LA-NSCLC between January 2005 and January 2016 were analyzed. A five immune features-based signature was then constructed using the nested repeat 10-fold cross validation with least absolute shrinkage and selection operator (LASSO) Cox regression model. Nomograms were then established for predicting prognosis. RESULTS: The immune signature combining five immuno-features was significantly associated with overall survival (OS) and progression-free survival (PFS) (P = 0.002 and P = 0.014, respectively) in patients with inoperable LA-NSCLC, and at a cutoff of -0.05 stratified patients into two groups with 5-year OS rates of 39.8 and 8.8%, and 2-year PFS rates of 22.2 and 5.5% for the high- and low-immune signature groups, respectively. Integrating immune signature, we proposed predictive nomograms that were better than the traditional TNM staging system in terms of discriminating ability (OS: 0.692 vs. 0.588; PFS: 0.672 vs. 0.586, respectively) or net weight classification (OS: 32.96%; PFS: 9.22%), suggesting that the immune signature plays a significant role in improving the prognostic value. CONCLUSION: Multiple immune features-based immune signature could effectively predict recurrence and survival of inoperable LA-NSCLC patients and complemented the prognostic value of the TNM staging system.

Development and validation of a nomogram prognostic model for esophageal cancer patients with oligometastases.

Platinum-based chemotherapy is recommended as the standard treatment for metastatic esophageal cancer (EC) patients; however, the outcome is poor. Oligometastasis is less aggressive and has limited growth potential. However, the prognostic factors for EC patients with oligometastases was largely unknown. Thus, we intend to determine the prognostic factors, and develop and validate nomograms for prediction of survival for EC patients with oligometastases. In this study, characteristics of 273 oligometastatic EC patients were analyzed using univariate and multivariate Cox models to determine the independent prognostic factors for progression-free survival (PFS) and overall survival (OS). The result showed that history of alcohol consumption, longer tumor, no local radiotherapy for EC, and no local treatment for metastases were independent factors for PFS. Sex, esophageal fistula, number of metastatic organs, and local radiotherapy for EC were independent prognostic factors for OS. On the basis of Cox models, the respective nomogram for prediction of PFS and OS was established with the corrected concordance index of 0.739 and 0.696 after internal cross-validation. In conclusion, local treatment for metastases and local radiotherapy for EC were demonstrated to be beneficial for oligometastatic EC patients, and the validated nomograms are valuable in prognosis prediction and could guide individualized management for these patients.

In vitro and in vivo evaluation of the safety and efficacy of a novel liquid fiducial marker for image-guided radiotherapy.

The true extent of a tumor is difficult to visualize, during radiotherapy, using current modalities. In the present study, the safety and feasibility of a mixture of N-butyl cyanoacrylate and lipiodol (NBCA/Lip) was evaluated in order to investigate the optimal combination for application as a fiducial marker for radiotherapy. Four combinations of NBCA/Lip injection (1:1-0.1, 1:1-0.15, 1:3-0.1 and 1:3-0.15 ml) were injected into the subcutaneous tissue of BALB/c mice. The changes in gross histopathology, body weight, skin score, marker volume, neutrophil and macrophage counts were observed to analyze the effects of the different mixing ratios and injection volumes, in order to identify the best combination. Evaluation according to the International Organization for Standardization criteria was further conducted in order to test the biocompatibility of the mixture, including an acute systematic assay with mice, cytotoxicity with L929 fibroblasts and delayed-type hypersensitivity tests with guinea pigs and an intradermal test with rabbits. The results revealed that at the seventh week, 42 markers (42/48; 87.5%) were still visible using computed tomography (CT) imaging. No serious adverse effects were observed throughout the study period; however, the combination of 1:1-0.1 ml had the lowest body weight and worst skin score. A review of the histopathological reaction to NBCA/Lip revealed a combination of acute inflammation, chronic inflammation, granulation tissue, foreign-body reaction and fibrous capsule formation. The 1:1 NBCA combination ratio resulted in the most intense tissue repair reaction and a slower degradation rate of markers. In general, the combination of 1:3-0.15 ml had a better fusion with local tissue, maintained a stable imaging nodule on CT images for 7 weeks and the final biocompatibility test demonstrated its safety. Overall, the findings of the present study demonstrated NBCA/Lip as a safe and feasible fiducial marker, when using the 1:3-0.15 ml combination.

A Novel Nomogram and Risk Classification System Predicting Radiation Pneumonitis in Patients With Esophageal Cancer Receiving Radiation Therapy.

PURPOSE: We initially aimed to ascertain the application value of inflammatory indexes in predicting severe acute radiation pneumonitis (SARP). Furthermore, a novel nomogram and risk classification system integrating clinicopathologic, dosimetric, and biological parameters were built to provide individualized risk assessment and accurate prediction of SARP in patients with esophageal cancer who received radiation therapy. METHODS AND MATERIALS: All data were retrospectively collected from 416 esophageal cancer patients in 2 participating institutes. A novel nomogram was constructed that forecasted SARP based on logistic regression analyses. The concordance index, calibration curves, and decision curve analyses were used by both internal and external validation to demonstrate discriminatory and predictive capacity. Moreover, a corresponding risk classification system was generated by recursive partitioning analysis. RESULTS: The Subjective Global Assessment score, pulmonary fibrosis score, planning target volume/total lung volume, mean lung dose, and ratio of change regarding systemic immune inflammation index at 4 weeks in the course of treatment were independent predictors of SARP and finally incorporated into our nomogram. The concordance index of nomogram for SARP prediction was 0.852, which showed superior discriminatory power (range, 0.604-0.712). Calibration curves indicated favorable consistency between the nomogram prediction and the actual outcomes. Decision curve analyses exhibited satisfactory clinical utility. A risk classification system was established to perfectly divide patients into 3 different risk groups, which were low-risk group (6.1%, score 0-158), intermediate-risk group (37.3%, score 159-280), and high-risk group (78.9%, score >280). CONCLUSIONS: The Subjective Global Assessment score, pulmonary fibrosis score, planning target volume/total lung volume, mean lung dose, and ratio of change regarding systemic immune inflammation index at 4 weeks were potential valuable markers in predicting SARP. The developed nomogram and corresponding risk classification system with superior prediction ability for SARP could assist in patient counseling and provide guidance when making treatment decisions.

Diagnostic and Predictive Value of Using RGD PET/CT in Patients with Cancer: A Systematic Review and Meta-Analysis.

The purpose of this study was to assess the diagnostic value of arginine-glycine-aspartic acid (RGD) PET/CT for tumor detection in patients with suspected malignant lesions and to determine the predictive performance of RGD PET/CT in identifying responders. Methods. The PubMed (Medline), EMBASE, Cochrane Library, and Web of Science databases were systematically searched for potentially relevant publications (last updated on July 28th, 2018) reporting the performance of RGD PET in the field of oncology. Pooled sensitivities, specificities, and diagnostic odds ratios (DORs) were calculated for parameters. The areas under the curve (AUCs) and Q⁎ index scores were determined from the constructed summary receiver operating characteristic (SROC) curve. We explored heterogeneity by metaregression. Results. Nine studies, five including 216 patients that determined diagnostic performance and three including 75 patients that determined the predictive value of parameters, met our inclusion criteria. The pooled sensitivity, pooled specificity, DOR, AUC, and Q⁎ index score of RGD PET/CT for the detection of underlying malignancy were 0.85 (0.79-0.89), 0.93 (0.90-0.96), 48.35 (18.95-123.33), 0.9262 (standard error=0.0216), and 0.8606 for SUVmax and 0.86 (0.80-0.91), 0.92 (0.88-0.94), 40.49 (14.16-115.77), 0.9312 (SE=0.0177), and 0.8665 for SUVmean, respectively. The pooled sensitivity, pooled specificity, DOR, AUC, and Q⁎ index score of RGD PET/CT for identifying responders were 0.80 (0.59-0.93), 0.74 (0.60-0.85), 15.76 (4.33-57.32), 0.8682 (0.0539), and 0.7988, respectively, for SUVmax at baseline. Conclusion. The interesting but preliminary data in this meta-analysis demonstrate that RGD PET/CT may be an ideal diagnostic tool for detecting underlying malignancies in patients suspected of having tumors and may be able to efficiently predict short-term outcomes.

Effects of respiratory motion on volumetric and positional difference of GTV in lung cancer based on 3DCT and 4DCT scanning.

Differences in gross target volume (GTV) and central point positions among moving lung cancer models constructed by CT scanning at different frequencies were compared, in order to explore the effect of different respiratory frequencies on the GTV constructions in moving lung tumors. Eight models in different shapes and sizes were established to stimulate lung tumors. The three-dimensional computed tomography (3DCT) and four-dimensional computed tomography (4DCT) scanning were performed at 10, 15 and 20 times/min in different models. Differences in GTV volumes and central point positions at different motion frequencies were compared by means of GTV3Ds (GTV3D-10, GTV3D-15, GTV3D-20) and IGTV4Ds (IGTV4D-10, IGTV4D-15, IGTV4D-20). Volumes of GTV3D-10, GTV3D-15, GTV3D-20 were 12.41±14.26, 10.38±11.18 and 12.50±15.23 cm3 respectively (P=0.687). Central point coordinates in the x-axis direction were -8.16±96.21, -8.57±96.08 and -8.56±95.73 respectively (P=0.968). Central point coordinates in the y-axis direction were 108.22±25.03, 110.41±22.47 and 109.04±24.24 (P=0.028). Central point coordinates in the z-axis direction were 65.19±13.68, 65.43±13.40 and 65.38±13.17 (P=0.902). The difference was significant in the y-axis direction (P=0.028). Volumes of IGTV4D-10, IGTV4D-15, IGTV4D-20 were 17.78±19.42, 17.43±19.56 and 17.44±18.80 cm3 (P=0.417). Central point coordinates in the x-axis direction were -7.73±95.93, -7.86±95.56 and -7.92±95.14 (P=0.325). Central point coordinates in the y-axis direction were 109.41±24.54, 109.60±24.13 and 109.16±24.28 (P=0.525). Central point coordinates in the z-axis direction were 65.52±13.31, 65.59±13.39 and 65.51±13.34 (P=0.093). However, the central point position of GTV in the head and foot direction by 3DCT scanning was severely affected by the respiratory frequency.

Development and validation of a risk prediction model for radiotherapy-related esophageal fistula in esophageal cancer.

OBJECTIVES: We aimed to identify the risk factors and provide a nomogram for the prediction of radiotherapy-related esophageal fistula in patients with esophageal cancer (EC) using a case-control study. PATIENTS AND METHODS: Patients with esophageal fistula who received radiotherapy or chemoradiotherapy between 2003 and 2017 were retrospectively collected in two institutions. In the training cohort (TC), clinical, pathologic, and serum data of 136 patients (cases) who developed esophageal fistula during or after radiotherapy were enrolled and compared with 272 controls (1:2 matched with the diagnosis time of EC, sex, marriage, and race). After the univariable and multivariable logistic regression analyses, the independent risk factors were identified and incorporated into a nomogram. Then the nomogram for the risk prediction was externally validated in the validation cohort (VC; 47 cases and 94 controls) using bootstrap resampling. RESULTS: Multivariable analyses demonstrated that ECOG PS, BMI, T4, N2/3 and re-radiotherapy were independent factors for esophageal fistula. Then a nomogram was constructed with the C-index of 0.805 (95% CI, 0.762-0.848) for predicting the risk of developing esophageal fistula in EC patients receiving radiotherapy. Importantly, the C-index maintained 0.764 (95% CI, 0.683-0.845) after the external validation. CONCLUSIONS: We created and externally validated the first risk nomogram of esophageal fistula associated with radiotherapy. This will aid individual risk stratification of patients with EC developing esophageal fistula.