Early, non-invasive detection of radiation-induced lung injury using PET/CT by targeting CXCR4.

PURPOSE: Radiation-induced lung injury (RILI) is a severe side effect of radiotherapy (RT) for thoracic malignancies and we currently lack established methods for the early detection of RILI. In this study, we synthesized a new tracer, [18F]AlF-NOTA-QHY-04, targeting C-X-C-chemokine-receptor-type-4 (CXCR4) and investigated its feasibility to detect RILI. METHODS: An RILI rat model was constructed and scanned with [18F]AlF-NOTA-QHY-04 PET/CT and [18F]FDG PET/CT periodically after RT. Dynamic, blocking, autoradiography, and histopathological studies were performed on the day of peak uptake. Fourteen patients with radiation pneumonia, developed during or after thoracic RT, were subjected to PET scan using [18F]AlF-NOTA-QHY-04. RESULTS: The yield of [18F]AlF-NOTA-QHY-04 was 28.5-43.2%, and the specific activity was 27-33 GBq/µmol. [18F]AlF-NOTA-QHY-04 was mainly excreted through the kidney. Significant increased [18F]AlF-NOTA-QHY-04 uptake in the irradiated lung compared with that in the normal lung in the RILI model was observed on day 6 post-RT and peaked on day 14 post-RT, whereas no apparent uptake of [18F]FDG was shown on days 7 and 15 post-RT. MicroCT imaging did not show pneumonia until 42 days post-RT. Significant intense [18F]AlF-NOTA-QHY-04 uptake was confirmed by autoradiography. Immunofluorescence staining demonstrated expression of CXCR4 was significantly increased in the irradiated lung tissue, which correlated with results obtained from hematoxylin-eosin and Masson's trichrome staining. In 14 patients with radiation pneumonia, maximum standardized uptake values (SUVmax) were significantly higher in the irradiated lung compared with those in the normal lung. SUVmax of patients with grade 2 RILI was significantly higher than that of patients with grade 1 RILI. CONCLUSION: This study indicated that [18F]AlF-NOTA-QHY-04 PET/CT imaging can detect RILI non-invasively and earlier than [18F]FDG PET/CT in a rat model. Clinical studies verified its feasibility, suggesting the clinical potential of [18F]AlF-NOTA-QHY-04 as a PET/CT tracer for early monitoring of RILI.

The prognostic value of 11th Japanese classification and 8th AJCC staging systems in Chinese patients with esophageal squamous cell carcinoma.

BACKGROUND: Two staging systems, the 8th staging system by the American Joint Committee on Cancer (AJCC) and the 11th Japanese classification by Japan Esophageal Society (JES), are currently applied in the clinic for predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC). The differences between the two staging systems have been widely researched. However, little studies focus on the differences in specific staging between the two systems. Therefore, we aimed to compare the performance of different staging in predicting overall survival (OS) of Chinese patients with ESCC. METHODS: This retrospective study included 268 patients who underwent radical esophagectomy and mediastinal lymph node dissection for ESCC between January 2008 and December 2013. Patients were staged by the 8th AJCC and 11th JES staging systems. OS was estimated using the Kaplan-Meier method and compared between N stages and between stage groupings using the log-rank test. Cox proportional hazards regression analysis was performed to identify factors independently related to outcome. Further, we compared the concordance indexes (C-indexes) of the two staging systems. RESULTS: The mean age was 61.25 ± 7.056 years, median follow-up was 44.82 months, and 5-year OS rate was 47%. The OS was well predicted by the 8th AJCC N staging (P < 0.001) and the 11th JES N staging (P < 0.001), with a c-index of 0.638 (95% CI: 0.592-0.683) for AJCC N staging and 0.627 (95% CI: 0.583-0.670) for JES N staging (P = 0.13). In addition, the OS was also well predicted by stage groupings of the 8th AJCC (P < 0.001) and the 11th JES systems (P < 0.001), with a c-index of 0.658 (95% CI: 0.616-0.699) for 8th AJCC stage grouping and 0.629 (95% CI: 0.589-0.668) for the11th JES stage grouping (P = 0.211). CONCLUSIONS: The prognostic effect of 11th JES staging system is comparable with that of AJCC 8th staging system for patients with ESCC. Therefore, both systems are applicable to clinical practice.

Brain injury after cranial radiotherapy combined with immunotherapy for brain metastases in lung cancer: a retrospective study.

Aim: To explore whether immune checkpoint inhibitors (ICIs) increase the incidence of radiation-induced brain injury in lung cancer patients with brain metastases. Methods: According to whether they received ICIs within 6 months before and after cranial radiotherapy (CRT), all patients were divided into two groups: ICIs + CRT group and CRT + non-ICIs group. Results: The incidence of radiation necrosis (RN) in the CRT + ICIs group was 14.3%, while that in the CRT + non-ICIs group was 5.8% (p = 0.090). If ICIs were used within 3 months of CRT, there was statistical significance. A maximum diameter of brain metastasis >3.3 cm and cumulative radiation dose of metastatic lesions >75.7 Gy were risk factors for RN. Conclusion: ICIs could increase the risk of RN, especially when used within 3 months of CRT.

The Glutaminase Inhibitor Compound 968 Exhibits Potent In vitro and In vivo Anti-tumor Effects in Endometrial Cancer.

BACKGROUND: Glutamine is one of the primary nutrients utilized by cancer cells for energy production and biosynthesis. Hence, interfering with glutamine metabolism may impose anti-tumor effects. OBJECTIVE: In this study, we assessed the anti-tumorigenic effects of glutaminase-1 enzyme (GLS1) inhibition in endometrial cancer in vitro and in vivo. METHODS: The human endometrial cancer cell lines Ishikawa and HEC-1B were used. The effects of compound 968 on cell proliferation, cell cycle, apoptosis, cellular stress, and AKT/mTOR pathway inhibition were assessed. The synergistic effects of compound 968 and paclitaxel were also analyzed. The in vivo effect of compound 968 was evaluated using tumor xenografts. RESULTS: We found that the GLS1-targeting compound 968 was able to reduce cancer cell proliferation in a dose- and time-dependent manner. Compound 968 combined with a low concentration of paclitaxel showed stronger inhibitory effects. Further analyses indicated that compound 968 induced cell cycle arrest at the G1 phase, as well as increased the production of cellular reactive oxygen species (ROS) and promoted cellular stress and cancer cell apoptosis. Additionally, the treatment of endometrial cancer with compound 968 downregulated the expression of GLS1 and cyclin D1 and upregulated the expression of P21 and E-cadherin. Moreover, the treatment of endometrial cancer cells with compound 968 significantly reduced the levels of phospho-S6 ribosomal protein and phospho-AKT (Ser473), indicative of AKT/mTOR/S6 signaling pathway inhibition. In xenograft mouse models of endometrial cancer, compound 968 significantly suppressed tumor growth. In addition, western blotting analysis indicated that GLS1 expression was upregulated in human endometrial cancer tissues. CONCLUSION: Compound 968 may be a promising approach for the management of human endometrial cancer.

Effectivity of involved-field radiotherapy for recurrent brain metastasis in patients with small-cell lung cancer.

Objectives: To investigate the outcome difference of whole brain radiotherapy (WBRT) and involved-field radiotherapy (IFRT) in limited-stage small-cell lung cancer (LS-SCLC) patients with recurrent brain metastases (BMs) after prophylactic cranial irradiation (PCI). Methods: A retrospective analysis was carried out in 68 LS-SCLC patients who underwent WBRT or IFRT owing to the occurrence of recurrent BMs after PCI from 2009 to 2020. Results: The median overall survival (OS) of all patients was 11.43 months [95% confidence interval (CI) 9.39-13.48 months]. In the paired comparison of OS, the IFRT group had a significantly longer survival time than the WBRT group in all patients [17.80 months vs. 8.47 months; hazard ratio (HR), 0.393, 95% CI, 0.213-0.728; P = 0.002] and 46 matched patients (18.23 months vs. 8.73 months; HR, 0.411, 95% CI, 0.195-0.865; P = 0.019). In terms of the intra-cranial progression-free survival (iPFS), there was no significant difference between the WBRT group and IFRT group before matching (5.93 months vs. 7.30 months; HR, 0.644, 95% CI, 0.373-1.112; P = 0.111); similarly, no statistical difference was detected between the WBRT group and IFRT group after matching (5.33 months vs. 8.10 months; HR, 0.623, 95% CI, 0.323-1.199; P = 0.152). Meanwhile, of the 41 patients with symptoms, 27 cases (65.9%) had symptom relief, showing tolerable toxicity without unexpected toxicity during the observation. Conclusions: Compared with WBRT, IFRT exhibits better survival benefits for LS-SCLC patients with recurrent BMs after PCI. Re-irradiation for BMs exhibits advantages of symptom relief and tolerable side effects.

Potential 18F-RGD PET/CT and DCE-MRI Imaging-Based Biomarkers for Postoperative Survival Prediction Among Patients With Newly Diagnosed Glioblastoma Treated With Bevacizumab and Chemoradiotherapy.

Purpose: To investigate the ability of potential imaging biomarkers based on 18F-AlF-NOTA-PRGD2 positron emission tomography/computed tomography (18F-RGD PET/CT) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) imaging to predict the response to bevacizumab combined with conventional therapy in postoperative newly diagnosed glioblastoma. Methods: Twenty patients with newly diagnosed with glioblastoma after surgery were prospectively enrolled to receive bevacizumab plus conventional concurrent radiotherapy and temozolomide (CCRT). 18F-RGD PET/CT and DCE-MRI were performed at baseline, week 3, and week 10 for each patient. Statistical methods included the analysis of variance (ANOVA), Kaplan-Meier method and Cox proportional hazard analysis. Results: All patients completed CCRT plus bevacizumab therapy without interruption. The median follow-up time was 33.9 months (95% confidence interval [CI], 28.3-39.5 months). The median progression-free survival (PFS) and overall survival (OS) was 9.66 months (95% CI, 6.20-13.12 months) and 15.89 months (95% CI, 13.89-17.78), respectively. Treatment was generally well tolerated, and there were no Treatment emergent adverse events (TEAEs) with a toxicity grade equal to or exceeding 3 or that led to termination of treatment or patient death.Over the treatment interval of bevacizumab therapy from week 3 to week 10, patients with a large decrease of SUVmean was associated with a better PFS with a hazard ratio (HR) of 6.562, 95% CI (1.318-32.667), p=0.022. According to Kaplan-Meier analysis, patients with a decrease in the SUVmean of more than 0.115 on 18F-RGD PET/CT had a longer PFS than those with a decrease in the SUVmean of 0.115 or less (12.25 months vs.7.46 months, p=0.009). For OS, only a small decrease of Ktrans was also found to have certain prognostic value (HR=0.986, 95% CI (0.975-0.998), p=0.023). Patients with a decrease in Ktrans larger than 37.03 (min-1) on DCE-MRI had worse OS than those with a decrease in Ktrans of 37.03 (min-1) or less (15.93 months vs. 26.42 months, p=0.044). Conclusion: 18F-RGD PET/CT and DCE-MRI may be valuable in evaluating the response of glioblastoma to treatment with the combination of bevacizumab and CCRT, with a greater decrease in SUVmean predicting better PFS as well as a small decrease in Ktrans predicting improved OS.

Response Prediction to Concurrent Chemoradiotherapy in Esophageal Squamous Cell Carcinoma Using Delta-Radiomics Based on Sequential Whole-Tumor ADC Map.

Purpose: The purpose of this study was to investigate the association between the radiomics features (RFs) extracted from a whole-tumor ADC map during the early treatment course and response to concurrent chemoradiotherapy (cCRT) in patients with esophageal squamous cell carcinoma (ESCC). Methods: Patients with ESCC who received concurrent chemoradiotherapy were enrolled in two hospitals. Whole-tumor ADC values and RFs were extracted from sequential ADC maps before treatment, after the 5th radiation, and after the 10th radiation, and the changes of ADC values and RFs were calculated as the relative difference between different time points. RFs were selected and further imported to a support vector machine classifier for building a radiomics signature. Radiomics signatures were obtained from both RFs extracted from pretreatment images and three sets of delta-RFs. Prediction models for different responders based on clinical characteristics and radiomics signatures were built up with logistic regression. Results: Patients (n=76) from hospital 1 were randomly assigned to training (n=53) and internal testing set (n=23) in a ratio of 7 to 3. In addition, to further test the performance of the model, data from another institute (n=17) were assigned to the external testing set. Neither ADC values nor delta-ADC values were correlated with treatment response in the three sets. It showed a predictive effect to treatment response that the AUC values of the radiomics signature built from delta-RFs over the first 2 weeks were 0.824, 0.744, and 0.742 in the training, the internal testing, and the external testing set, respectively. Compared with the evaluated response, the performance of response prediction in the internal testing set was acceptable (p = 0.048). Conclusions: The ADC map-based delta-RFs during the early course of treatment were effective to predict the response to cCRT in patients with ESCC.

Pretreatment Thoracic CT Radiomic Features to Predict Brain Metastases in Patients With ALK-Rearranged Non-Small Cell Lung Cancer.

Objective: To identify CT imaging biomarkers based on radiomic features for predicting brain metastases (BM) in patients with ALK-rearranged non-small cell lung cancer (NSCLC). Methods: NSCLC patients with pathologically confirmed ALK rearrangement from January 2014 to December 2020 in our hospital were enrolled retrospectively in this study. Finally, 77 patients were included according to the inclusion and exclusion criteria. Patients were divided into two groups: BM+ were those patients who were diagnosed with BM at baseline examination (n = 16) or within 1 year's follow-up (n = 14), and BM- were those without BM followed up for at least 1 year (n = 47). Radiomic features were extracted from the pretreatment thoracic CT images. Sequential univariate logistic regression, LASSO regression, and backward stepwise logistic regression were used to select radiomic features and develop a BM-predicting model. Results: Five robust radiomic features were found to be independent predictors of BM. AUC for radiomics model was 0.828 (95% CI: 0.736-0.921), and when combined with clinical features, the AUC was increased (p = 0.017) to 0.909 (95% CI: 0.845-0.972). The individualized BM-predicting model incorporated with clinical features was visualized by the nomogram. Conclusion: Radiomic features extracted from pretreatment thoracic CT images have the potential to predict BM within 1 year after detection of the primary tumor in patients with ALK-rearranged NSCLC. The radiomics model incorporated with clinical features shows improved risk stratification for such patients.

Combined model of radiomics and clinical features for differentiating pneumonic-type mucinous adenocarcinoma from lobar pneumonia: An exploratory study.

Purpose: The purpose of this study was to distinguish pneumonic-type mucinous adenocarcinoma (PTMA) from lobar pneumonia (LP) by pre-treatment CT radiological and clinical or radiological parameters. Methods: A total of 199 patients (patients diagnosed with LP = 138, patients diagnosed with PTMA = 61) were retrospectively evaluated and assigned to either the training cohort (n = 140) or the validation cohort (n = 59). Radiomics features were extracted from chest CT plain images. Multivariate logistic regression analysis was conducted to develop a radiomics model and a nomogram model, and their clinical utility was assessed. The performance of the constructed models was assessed with the receiver operating characteristic (ROC) curve and the area under the curve (AUC). The clinical application value of the models was comprehensively evaluated using decision curve analysis (DCA). Results: The radiomics signature, consisting of 14 selected radiomics features, showed excellent performance in distinguishing between PTMA and LP, with an AUC of 0.90 (95% CI, 0.83-0.96) in the training cohort and 0.88 (95% CI, 0.79-0.97) in the validation cohort. A nomogram model was developed based on the radiomics signature and clinical features. It had a powerful discriminative ability, with the highest AUC values of 0.94 (95% CI, 0.90-0.98) and 0.91 (95% CI, 0.84-0.99) in the training cohort and validation cohort, respectively, which were significantly superior to the clinical model alone. There were no significant differences in calibration curves from Hosmer-Lemeshow tests between training and validation cohorts (p = 0.183 and p = 0.218), which indicated the good performance of the nomogram model. DCA indicated that the nomogram model exhibited better performance than the clinical model. Conclusions: The nomogram model based on radiomics signatures of CT images and clinical risk factors could help to differentiate PTMA from LP, which can provide appropriate therapy decision support for clinicians, especially in situations where differential diagnosis is difficult.

Therapeutic effect of osimertinib plus cranial radiotherapy compared to osimertinib alone in NSCLC patients with EGFR-activating mutations and brain metastases: a retrospective study.

BACKGROUND: The study aimed to compare the efficacy of osimertinib plus cranial radiotherapy (RT) with osimertinib alone in advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations and brain metastases (BMs). METHODS: The clinical data of advanced NSCLC patients with BMs who received osimertinib were retrospectively collected. The patients were assigned to one of the two groups according to the therapeutic modality used: the osimertinib monotherapy group or the osimertinib plus RT group. RESULTS: This was a retrospective study and 61 patients were included from December 2015 to August 2020. Forty patients received osimertinib monotherapy, and twenty-one patients received osimertinib plus RT. Radiotherapy included whole-brain radiation therapy (WBRT, n = 14), WBRT with simultaneous integrated boost (WBRT-SIB, n = 5) and stereotactic radiosurgery (SRS, n = 2). The median number of prior systemic therapies in the two groups was one. Intracranial and systemic ORR and DCR were not significantly different between the two groups. No difference in iPFS was observed between the two groups (median iPFS: 16.67 vs. 13.50 months, P = 0.836). The median OS was 29.20 months in the osimertinib plus RT group compared with 26.13 months in the osimertinib group (HR = 0.895, P = 0.826). In the L858R mutational subgroup of 31 patients, the osimertinib plus RT group had a longer OS (P = 0.046). In the exon 19 deletion mutational subgroup of 30 patients, OS in the osimertinib alone group was longer than that in the osimertinib plus RT group (P = 0.011). The incidence of any-grade adverse events was not significantly different between the osimertinib plus RT group and the osimertinib alone group (47.6% vs. 32.5%, P = 0.762). However, six patients (28.5%) experienced leukoencephalopathy in the osimertinib plus RT group, and 50% (3/6) of the leukoencephalopathy was greater than or equal to grade 3. CONCLUSION: The therapeutic effect of osimertinib with RT was similar to that of osimertinib alone in EGFR-positive NSCLC patients with BM. However, for patients with the L858R mutation, osimertinib plus RT could provide more benefit than osimertinib alone.

Inter-observer variations of the tumor bed delineation for patients after breast conserving surgery in preoperative magnetic resonance and computed tomography scan fusion.

PURPOSE: Tumor bed (TB) delineation based on preoperative magnetic resonance imaging (pre-MRI) fused with postoperative computed tomography (post-CT) were compared to post-CT only to define pre-MRI may aid in improving the accuracy of delineation. METHODS AND MATERIALS: The pre-MRI imaging of 10 patients underwent radiotherapy (RT) after breast conserving surgery (BCS) were reviewed. Post-CT scans were acquired in the same prone position as pre-MRI. Pre-MRI and post-CT automatically match and then manual alignment was given to enhance fusion consistency. Three radiation oncologists and 2 radiologists delineated the clinical target volume (CTV) for CT-based. The gross target volume (GTV) of pre-MRI-based was determined by the volume of tumor acquired with 6 sequences: T1, T2, T2W-SPAIR, DWI, dyn-eTHRIVE and sdyn-eTHRIVE, expended 10 mm to form the CTV-pre-MRI. Planning target volume (PTV) for each sequence was determined by CTV extended 15 mm, trimmed to 3 mm from skin and the breast-chest wall interface. The variability of the TB delineation were developed as follows: the mean volume, conformity index (CI) and dice coefficient (DC). RESULTS: The mean volumes of CTV and PTV delineated with CT were all larger than those with pre-MRI. The lower inter-observer variability was observed from PTV, especially in sdyn-eTHRIVE in all sequences. For each sequence of pre-MRI, all DCs were larger than post-CT, and the largest DC was observed by sdyn-eTHRIVE sequence fusion to post-CT. The overlap for PTV was significantly improved in the pre-MRI-based compared with the CT-based. CONCLUSIONS: TB volumes based on pre-MRI were smaller than post-CT with CVS increased. Pre-MRI provided a more precise definition of the TB with observers performed a smaller inter-observer variability than CT. Pre-MRI, especially in sdyn-eTHRIVE sequence, should help in reducing treatment volumes with the improved accuracy of TB delineation of adjuvant RT of breast cancer.

Imaging Biomarkers to Predict and Evaluate the Effectiveness of Immunotherapy in Advanced Non-Small-Cell Lung Cancer.

OBJECTIVE: We aimed to identify imaging biomarkers to assess predictive capacity of radiomics nomogram regarding treatment response status (responder/non-responder) in patients with advanced NSCLC undergoing anti-PD1 immunotherapy. METHODS: 197 eligible patients with histologically confirmed NSCLC were retrospectively enrolled from nine hospitals. We carried out a radiomics characterization from target lesions (TL) approach and largest target lesion (LL) approach on baseline and first follow-up (TP1) CT imaging data. Delta-radiomics feature was calculated as the relative net change in radiomics feature between baseline and TP1. Minimum Redundancy Maximum Relevance (mRMR) and Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression were applied for feature selection and radiomics signature construction. RESULTS: Radiomics signature at baseline did not show significant predictive value regarding response status for LL approach (P = 0.10), nor in terms of TL approach (P = 0.27). A combined Delta-radiomics nomogram incorporating Delta-radiomics signature with clinical factor of distant metastasis for target lesions had satisfactory performance in distinguishing responders from non-responders with AUCs of 0.83 (95% CI: 0.75-0.91) and 0.81 (95% CI: 0.68-0.95) in the training and test sets respectively, which was comparable with that from LL approach (P = 0.92, P = 0.97). Among a subset of those patients with available pretreatment PD-L1 expression status (n = 66), models that incorporating Delta-radiomics features showed superior predictive accuracy than that of PD-L1 expression status alone (P <0.001). CONCLUSION: Early response assessment using combined Delta-radiomics nomograms have potential advantages to identify patients that were more likely to benefit from immunotherapy, and help oncologists modify treatments tailored individually to each patient under therapy.

Comparison of postoperative CT- and preoperative MRI-based breast tumor bed contours in prone position for radiotherapy after breast-conserving surgery.

OBJECTIVES: To compare the target volume of tumor bed defined by postoperative computed tomography (post-CT) in prone position registered with or without preoperative magnetic resonance imaging (pre-MRI). METHODS: A total of 22 patients were included with early-stage breast invasive ductal cancer, who have undergone breast-conservative surgery and received the pre-MRI and post-CT in prone position. The MRI sequences (T1W, T2W, T2W-SPAIR, DWI, dyn-eTHRIVE, sdyn-eTHRIVE) were delineated and manually registered to CT, respectively. The clinical target volumes (CTVs) and planning target volumes (PTVs) were contoured on CT and different MRI sequences, respectively. Differences were measured in terms of consistence index (CI), dice coefficient (DC), geographical miss index (GMI), and normal tissue index (NTI). RESULTS: The differences of delineation volumes among CT and MRIs were significant, both in the CTVs (p = 0.035) and PTVs (p < 0.001). The values of CI and DC for sdyn-eTHRIVE registration to CT were the largest among all MRI sequences, but GMI and NTI were the smallest. No obvious linear correlation (p > 0.05) between the CI derived from the registration of CT and sdyn-eTHRIVE of CTV with the breast volume, the cavity visualization score (CVS) of CT, time interval from surgery to CT simulation, the maximum diameter of the intraoperative mass, and the number of titanium clips, respectively. CONCLUSIONS: The CTVs and PTVs in MRI sequences were all smaller than those in CT. The pre-MRI, especially the sdyn-eTHRIVE, could be used to optimize the post-CT-based target delineation of breast cancer. KEY POINTS: • Registered pre-MRI to post-CT in order to improve the accuracy of target volume delineation of breast cancer. • The CTVs and PTVs in MRI sequences were all smaller than those in CT. • The sdyn-eTHRIVE of pre-MRIs may be a better choice to improve the delineation of CT-based CTV and PTV.

Risk stratification in GIST: shape quantification with CT is a predictive factor.

BACKGROUND: Tumor shape is strongly associated with some tumor's genomic subtypes and patient outcomes. Our purpose is to find the relationship between risk stratification and the shape of GISTs. METHODS: A total of 101 patients with primary GISTs were confirmed by pathology and immunohistochemistry and underwent enhanced CT examination. All lesions' pathologic sizes were 1 to 10 cm. Points A and B were the extremities of the longest diameter (LD) of the tumor and points C and D the extremities of the small axis, which was the longest diameter perpendicular to AB. The four angles of the quadrangle ABCD were measured and each angle named by its summit (A, B, C, D). For regular lesions, we took angles A and B as big angle (BiA) and small angle (SmA). For irregular lesions, we compared A/B ratio and D/C ratio and selected the larger ratio for analysis. The chi-square test, t test, ROC analysis, and hierarchical or binary logistic regression analysis were used to analyze the data. RESULTS: The BiA/SmA ratio was an independent predictor for risk level of GISTs (p = 0.019). With threshold of BiA at 90.5°, BiA/SmA ratio at 1.35 and LD at 6.15 cm, the sensitivities for high-risk GISTs were 82.4%, 85.3%, and 83.8%, respectively; the specificities were 87.1%, 71%, and 77.4%, respectively; and the AUCs were 0.852, 0.818, and 0.844, respectively. LD could not effectively distinguish between intermediate-risk and high-risk GISTs, but BiA could (p < 0.05). Shape and Ki-67 were independent predictors of the mitotic value (p = 0.036 and p < 0.001, respectively), and the accuracy was 87.8%. CONCLUSIONS: Quantifying tumor shape has better predictive efficacy than LD in predicting the risk level and mitotic value of GISTs, especially for high-risk grading and mitotic value > 5/50HPF. KEY POINTS: • The BiA/SmA ratio was an independent predictor affecting the risk level of GISTs. LD could not effectively distinguish between intermediate-risk and high-risk GISTs, but BiA could. • Shape and Ki-67 were independent predictors of the mitotic value. • The method for quantifying the tumor shape has better predictive efficacy than LD in predicting the risk level and mitotic value of GISTs.

Malignant jejunal gastrointestinal stromal tumor with history of prostate cancer: A case report.

RATIONALE: The problem of the coexistence of gastrointestinal stromal tumor (GIST) with other neoplasms is complex, and carcinomas of prostate is one of the common types of GIST-associated cancers. Doubling time of GIST is about 3.9 months for high-risk GIST, and the treatment paradigm for GIST has required the integration of surgery and molecular therapy. PATIENT CONCERNS: A 70-year-old man with postoperative history of prostate cancer experienced fast-growing malignant jejunal GIST with multiple peritoneal metastases within 1 year. DIAGNOSES: Enhanced computed tomography (CT) detected a neoplasm of small intestine with multiple peritoneal nodules and postoperative pathology confirmed GIST. INTERVENTIONS: Oral imatinib after surgery, at 400 mg per day, was used for 4 years. OUTCOMES: The patient remains well, and the peritoneal nodules located in front of the rectum disappeared gradually. LESSONS: Physicians should be aware of possibility of GIST in patients with prostate cancer and can perform abdominal examination in these patients. For postoperative patients with prostate cancer, an yearly or half-yearly abdominal and pelvic cavity examination can be performed. Suspicion and timely work-up is necessary in these postoperative prostate cancer patients, especially when they have abdominopelvic pain.

Lymph node metastasis outside of a tumor-bearing lobe in primary lung cancer and the status of interlobar fissures: The necessity for removing lymph nodes from an adjacent lobe.

The new Tumor Node Metastasis staging system does not recognize fissure status with respect to adjacent lobe invasion (ALI) in lung cancer. Furthermore, no specific surgical strategies have been recommended for lymph node dissections around adjacent nontumor-bearing lobes (NTBLs) according to fissure status. Therefore, this study was undertaken to investigate the necessity of removing additional adjacent lobe lymph nodes in patients with nonsmall cell lung cancer (NSCLC) for lesions limited to in the vicinity of the interlobar fissure.From August 2013 to March 2015, the records of 332 patients, who underwent systematic mediastinal lymph node dissection, were reviewed in this retrospective study. The bronchial lymph nodes had been subjected to pathological examination, and the status of the fissures was also recorded. A statistical analysis was performed to identify the significant predictors of lymph node metastasis.The patients were divided into a nonadjacent lobe invasion (NALI) group (n = 295) and an ALI group (n = 37). There was a significant difference in tumors with pN2 disease between the ALI and NALI groups (37.8% vs 8.8%, P = .001). ALI tumors had significantly more frequent pleural involvement than NALI tumors (62.2% vs 43.1%, P = .035). The frequency of N2 involvement among tumors invading across the complete fissure was higher than that of the tumors invading across the incomplete fissure (44.4% vs 14.3%, P = .015). However, the frequency of N1 involvement among tumors invading across the incomplete fissure was not statistically different than that of tumors not invading across incomplete fissure (32.1% vs 24.2%, P = .357). Regarding lymph node metastasis in NTBL, 15 (12.7%) patients had lymph node metastases in NTBLs. Pleural involvement was an independent predictor of lymph node metastasis in an NTBL.A greater frequency of N2 lymph nodes existed in NSCLC with invading adjacent lobe across complete fissure, extensive lymphatic resection within the hilum, and NTBL in tumors with pleural involvement are justifiable and necessary.

Long non-coding RNA EPIC1 promotes cholangiocarcinoma cell growth.

Cholangiocarcinoma (CCA) is the as the most frequently observed biliary tract malignancy, which has low survival rate in addition to constrained treatment options. However, the fundamental molecular mechanism underlying malignant progression of CCA is quite ambiguous. Recent studies reported that long non-coding RNA (lncRNA) might play critical roles in regulating chemo-resistant of multiple types of cancer. In this study, our results indicate that the LncRNA-EPIC1 expression were significantly increased in cholangiocarcinoma tissues, compared to adjacent normal tissues. And also, its expression also increased in several CCA cancer cell lines than that in human normal immortalized cholangiocyte cell. Loss-and-gain of Lnc-EPIC1 contributes to the CCA cell growth, colony formation, cell apoptosis and also cell cycle. Myc has been reported to directly interact with Lnc-EPIC1 in several cancer cells. Myc targets, including Cyclin A/D and CDK9 were downregulated by Lnc-EPIC1 siRNA. Myc knockout also suppresses the CCA cell growth, colony formation and cell apoptosis. However, Lnc-EPIC1 knockdown failed to enhance the Myc-KO-induced suppression of CCA tumor progression. RNA immunoprecipitation (RIP) results showed the direct interaction between Lnc-EPIC1 and Myc. Taken together, our results show that Lnc-EPIC1 promotes CCA cancer progression by targeting Myc.

The LncRNA H19/miR-193a-3p axis modifies the radio-resistance and chemotherapeutic tolerance of hepatocellular carcinoma cells by targeting PSEN1.

This study was designated to verify if the lncRNA H19/miR-193a-3p axis would play a regulatory role in the radio-/chemo-resistances of HCC cells through targeting PSEN1. Within the study, five human HCC cell lines were prepared, including Bel-7402, HepG2, Hep3b, QGY-7703, and SMMC-7721. Moreover, docetaxel (DT), paclitaxel (Pt), vinorelbine (Vb), and 5-fluorouracil (5-Fu) were managed as the chemo-therapeutics, and single-dose X-rays were performed as radio-therapies. Besides, lncRNA H19 and miR-193a-3p were detected by qRT-PCR and Western blot were implemented to quantify the expressional levels of PSEN1, Ku80, γ-H2AX, and RAD51. Luciferase reporter gene assay was advanced to verify the targeted relationship between lncRNA H19 and miR-193a-3p. As a consequence, QGY-7703 and Bel-7402 were, respectively, the most radiation-sensitive and radiation-proof cell lines, and Bel-7402 was associated with the highest resistances to DT, Pt, Vb, and 5-FU. The restrained lncRNA H19 and over-expressed miR-193a-3p expressions tended to significantly elevate the survival rate and proliferation of Bel-7402 cells, when they were exposed to radiation and subject to chemo-therapies. The lncRNA H19 was also found to directly target miR-193a-3p in inducing the HCC development. PSEN1 appeared to be subject to the modification of lncRNA H19 and miR-193a-3p in its acting on the survival rates and proliferative abilities of HCC cells. The lncRNA H19/miR-193a-3p/PSEN1 axis could be regarded as the treatment targets for HCC, so as to further improve the treatment efficacy of chemo- and radio-therapies for HCC.

Weaker Functional Connectivity Strength in Patients with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is related to cognitive impairments and increased risk for dementia. Neuroimaging studies have demonstrated T2DM-related brain structural and functional changes which are partly associated to the cognitive decline. However, few studies focused on the early neuroimaging findingsin T2DM patients. In this study, a data-driven whole-brain resting state functional connectivity strength (rsFCS) methodwas used to evaluate resting functional changes in 53 T2DM patients compared with 55 matched healthy controls (HCs), and to detect the associations between the rsFCSchanges and cognitive functions in T2DM patients. The T2DM patients exhibited weaker long-range rsFCS in the right insula and weaker short-range rsFCS in the right supramarginalgyrus (SG) compared with the HCs. Additionally, seed-based functional connectivity (FC) analysis revealed weaker FC between the right insula and the bilateral superior parietal lobule (SPL), and between the right SG and the bilateral supplementary motor area (SMA)/right SPL in T2DM patientscompared with the HCs. In T2DM patients, negative correlation was found between the long-range rsFCS in the right insula and HbA1c levels; and the FC between the right SG and the bilateral SMA negatively correlated with TMT-A scores. Our results indicated that the rsFCS alteration occurredbefore obvious cognitive deficits in T2DM patients, which might be helpful for understanding the neuromechanism of cognitive declines in T2DM patients.

Texture-based classification of different single liver lesion based on SPAIR T2W MRI images.

BACKGROUND: To assess the feasibility of texture analysis (TA) based on spectral attenuated inversion-recovery T2 weighted magnetic resonance imaging (SPAIR T2W-MRI) for the classification of hepatic hemangioma (HH), hepatic metastases (HM) and hepatocellular carcinoma (HCC). METHODS: The SPAIR T2W-MRI data of 162 patients with HH (n=55), HM (n=67) and HCC (n=40) were retrospectively analyzed. We used two independent cohorts for training (n = 112 patients) and validation (n = 50 patients). The TA was performed and textual parameters derived from the gray level co-occurrence matrix (GLCM), gray level gradient co-occurrence matrix (GLGCM), gray-level run-length matrix (GLRLM), Gabor wavelet transform (GWTF), intensity-size-zone matrix (ISZM), and histogram features were calculated. The capacity of each parameter to classify three types of single liver lesions was assessed using the Kruskal-Wallis test. Specificity and sensitivity for each of the studied parameters were derived using ROC curves. Four supervised classification algorithms were trained with the most influential textural features in the classification of tumor types. The test datasets validated the reliability of the models. RESULTS: The texture analyses showed that the HH versus HM, HM versus HCC, and HH versus HCC could be differentiated by 9, 16 and 10 feature parameters, respectively. The model's misclassification rates were 11.7, 9.6 and 9.7% respectively. No texture feature was able to adequately distinguish among the three types of single liver lesions at the same time. The BP-ANN model had better predictive ability. CONCLUSION: Texture features of SPAIR T2W-MRI can classify the three types of single liver lesions (HH, HM and HCC) and may serve as an adjunct tool for accurate diagnosis of these diseases.