Purpose: Neoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer. Materials and Methods: A total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits. Results: Genetic alterations of PIK3CA were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including TERT, POLD1, NOS2, and FGFR3 was significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including BRCA1/2, TP53 and PALB2. Importantly, high tumor mutation burden, TP53 polymorphism (rs1042522), and KEAP1 mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse. Conclusion We report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence.

Background and objective Molecular targeted therapy has gradually become an important treatment for lung cancer, the aim of this research is to analyze the clinicopathologic features associated with the gene mutation status of epidermal growth factor receptor (EGFR), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) and Kirsten rat sarcoma viral oncogene (KARS) in non-small cell lung cancer (NSCLC) patients and determine the most likely populations to beneift from molecular target ther-apy treatment. Methods hTe mutation status of EGFR, EML4-ALK fusion gene, ROS1 and AKRS gene were determined by Real-time PCR, the relationship between clinical pathologic features and concomitant gene were analyzed withχ2 test by SPSS sotfware 19.0. Results A total of 514 specimens from Shandong tumor hospital were collected from NSCLC patients between January 2014 and May 2016. The total mutation rate of EGFR gene was 36.70%, major occurred in exon 19 (36.61%) and exon 21 (51.36%), respectively, and EGFR mutations usually occurred in female, non-smoking and adenocarcinoma patients (P<0.05). hTe total rearrangements rate of EML4-ALK fusion gene was 9.37%, EML4-ALK fusion gene usually occurred in younger age (≤60 yr) and non-smoking patients (P<0.05). Mutations were not related to gender and pathological type (P>0.05). ROS1 fusion gene was detected in 136 cases, the positive rate was 3.67%, all patients were 60 years old, and the difference was statistically signiifcant (P<0.05). Only 23 samples were tested AKRS gene mutations, two of them were positive and the posi-tive rate was 8.70%. hTey all occurred in non-smoker and adenocarcinoma patients. No mutation was detected to coexist in EGFR, EML4-ALK and AKRS gene mutation. Conclusion EGFR, EML4-ALK, ROS1 and KARS deifnes different molecular subset of NSCLC with distinct characteristic, which provides a new option for the clinical treatment of patients with NSCLC.

Background and purpose:The most clearly recognized benefit of neoadjuvant chemotherapy (NAC) is that it can increase the proportion of patients who can be treated with breast-conserving therapy (BCT). However, the shrinkage modes of the primary breast tumor after NAC have been conifrmed as a predictor of BCT rate and prognosis. This study is to evaluate the accuracy of MRI predicting the shrinkage mode of the primary breast tumor after NAC with three-dimensional reconstruction technique.Methods:Sixty-one women with pathologically proven solitary invasive ductal carcinoma (ⅡA-ⅢC) were recruited. Breast specimens were prepared with PMSS, and residual tumors were microscopically outlined, scanned and registered by PHOTOSHOP software. The 3D model of residual tumors was reconstructed with 3D-DOCTOR software based on pathology and MRI imaging characteristics to evaluate the shrinkage mode. We devided the pathological shrinkage modes into surgical pCR (no residual tumors), solitary lesions without surrounding lesions, multinodular lesions, solitary lesions with adjacent spotty lesions and diffuse lesions. Further, the clinical-pathological shrinkage modes were divided into 2 categories: distinct shrinkage mode (DSM, the longest diameter of the pathological residual tumors was less than 50% and ≤2 cm in comparison with the primary tumor before NAC) and non-distinct shrinkage mode (NDSM, the longest diameter of the pathological residual tumors was more than 50% and/or >2 cm in comparison with the primary tumor before NAC).Results:The surgical pCR, solitary lesions without surrounding lesions, multinodular lesions, solitary lesions with adjacent spotty lesions and diffuse lesions were observed in 23, 17, 5, 9, 7 and 18, 3, 13, 20, 7 patients by MRI and pathology, respectively (P=0.001). The accuracy, sensitivity and speciifcity of MRI for predicting pathological shrinkage modes were 86.2%, 65.6% and 91.4%, respectively. The DSM was observed in 36 (59.0%) patients by pathology, and 38 (62.3%) patients by MRI. Two methods had a high consistency in clinical-pathological shrinkage modes (κ=0.863,P=0.000). The accuracy, sensitivity and speciifcity of MRI for predicting clinical-pathological shrinkage modes were 91.0%, 64.0% and 94.8%, respectively. There was not a statistic difference in prediction between DSM and NDSM by MRI (P>0.05). Receiver operating characteristic (ROC) curve analysis showed an AUC of 0.928 (P=0.000) for MRI to predict the clinical-pathological shrinkage mode.Conclusion:Three-dimensional MRI reconstruction after NAC could simulate and predict spatial location of residual tumors, and can be helpful in selecting patients who received BCT after NAC with tumor downstaging.

Objective The aim of this study is to evaluate the shrinkage mode of the primary tumor in women with breast cancer after neoadjuvant chemotherapy ( NAC ) determined by part?mount sub?serial section ( PMSS) and three?dimensional ( 3D) reconstruction technique. Methods Eighty?six women with pathologically proven solitary invasive ductal carcinoma (ⅡA?ⅢC) were recruited. They were divided into two groups. Group A ( n=25) received half cycles of NAC and Group B ( n=61) received whole cycles of NAC. Breast specimen was prepared with PMSS, and residual tumors were microscopically outlined, scanned and registered by Photoshop software. The 3D model of residual tumors was reconstructed with 3D?Doctor software to evaluate the shrinkage mode. Further, the clinicpathologic shrinkage modes were divided into 2 categories:concentric shrinkage mode ( CSM, the longest diameter of the pathological residual tumors was less than 50% and ≤2 cm in comparison with the primary tumor before NAC ) , and non?concentric shrinkage mode ( NCSM, the longest diameter of the pathological residual tumors was more than 50% and/or>2 cm in comparison with the primary tumor before NAC) . Results Pathological shrinkage modes:Group A: modes Ⅰ,Ⅱ, andⅤwere observed in 1, 1, and 23 cases, respectively;Group B:modesⅠ,Ⅱ,Ⅲ,Ⅳ, and Ⅴwere observed in 18, 3, 12, 21, and 7 cases, respectively ( P<0.001) . The multivariate analysis showed that patients with lower primary tumor stage, PR(-) or mammographic malignant calcification before NAC(-) and lymph nodes down?staging after NAC were more likely to present with CSM after NAC ( P<0.05 for all). Conclusions The pathologic reconstruction of breast residual tumors can fully and three?dimensionally reveal the shrinkage mode of the primary breast tumor in women with breast cancer after NAC. PMSS and 3D reconstruction of pathology provide a new platform in this area. Primary tumor stage, PR expression and mammographic malignant calcification before NAC and lymph node down?staging after NAC are independent predictors of the clinicopathologic shrinkage mode.

Objective The aim of this study is to evaluate the shrinkage mode of the primary tumor in women with breast cancer after neoadjuvant chemotherapy ( NAC ) determined by part?mount sub?serial section ( PMSS) and three?dimensional ( 3D) reconstruction technique. Methods Eighty?six women with pathologically proven solitary invasive ductal carcinoma (ⅡA?ⅢC) were recruited. They were divided into two groups. Group A ( n=25) received half cycles of NAC and Group B ( n=61) received whole cycles of NAC. Breast specimen was prepared with PMSS, and residual tumors were microscopically outlined, scanned and registered by Photoshop software. The 3D model of residual tumors was reconstructed with 3D?Doctor software to evaluate the shrinkage mode. Further, the clinicpathologic shrinkage modes were divided into 2 categories:concentric shrinkage mode ( CSM, the longest diameter of the pathological residual tumors was less than 50% and ≤2 cm in comparison with the primary tumor before NAC ) , and non?concentric shrinkage mode ( NCSM, the longest diameter of the pathological residual tumors was more than 50% and/or>2 cm in comparison with the primary tumor before NAC) . Results Pathological shrinkage modes:Group A: modes Ⅰ,Ⅱ, andⅤwere observed in 1, 1, and 23 cases, respectively;Group B:modesⅠ,Ⅱ,Ⅲ,Ⅳ, and Ⅴwere observed in 18, 3, 12, 21, and 7 cases, respectively ( P<0.001) . The multivariate analysis showed that patients with lower primary tumor stage, PR(-) or mammographic malignant calcification before NAC(-) and lymph nodes down?staging after NAC were more likely to present with CSM after NAC ( P<0.05 for all). Conclusions The pathologic reconstruction of breast residual tumors can fully and three?dimensionally reveal the shrinkage mode of the primary breast tumor in women with breast cancer after NAC. PMSS and 3D reconstruction of pathology provide a new platform in this area. Primary tumor stage, PR expression and mammographic malignant calcification before NAC and lymph node down?staging after NAC are independent predictors of the clinicopathologic shrinkage mode.

OBJECTIVETo evaluate the accuracy of MRI for estimating residual tumor size after neoadjuvant chemotherapy (NAC) with three-dimensional (3D) reconstruction technique.

METHODSThis was a prospective study. The data of 61 patients with pathologically proven solitary invasive ductal carcinoma (IIA-IIIC) who had received 6 to 8 cycles of NAC from July 2010 to August 2013 was analyzed. All the patients were female, aging from 31 to 70 years with a median of 49 years. Breast specimen after surgery was prepared with part-mount sub-serial section, and residual tumors were microscopically outlined, scanned and registered by Photoshop software. The 3D model of pathological and MRI residual tumors was reconstructed with 3D-DOCTOR software. The longest diameter, maximum cross-section area and volume of the residual tumors determined using 3D MRI were compared with 3D pathological findings, and the associations between MRI and pathology were analyzed by Spearman rank correlation and Bland-Altman analysis.

RESULTSThe longest diameter, maximum cross-section area and volume of the residual tumors after NAC measured by MRI and pathology was highly correlated (r=0.942, 0.941, 0.903, all P=0.00). MRI appears to underestimate pathology in the longest diameter, maximum cross-section area, but slightly overestimate in volume, and two methods had a good consistence (MD=0.3 cm, 95% CI: -1.43 to 1.9 cm; MD=1.39 cm², 95% CI: -9.55 to 12.34 cm²; MD=-0.433 cm³, 95% CI: -7.065 to 6.199 cm³).

CONCLUSION3D MRI reconstruction after NAC could accurately detects the residual tumors after neoadjuvant chemotherapy, and contribute to select patients who received breast conserving therapy after NAC with tumor downstaging.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; diagnosis ; drug therapy ; Female ; Humans ; Imaging, Three-Dimensional ; Magnetic Resonance Imaging ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm, Residual ; diagnosis ; Prospective Studies ; Tomography, X-Ray Computed

OBJECTIVEThe aim of this study was to retrospectively investigate the multi-detector computed tomography (MDCT) features of preinvasive lesions and minimally invasive adenocarcinoma (MIA) appearing as ground-glass nodules (GGNs), and to analyze their significance in differential diagnosis.

METHODSThe pathological data and MDCT images of 111 GGNs in 93 patients were reviewed and analyzed retrospectively, to identify the differentiating CT features between preinvasive lesions and MIA and to evaluate their differentiating accuracy.

RESULTSIn the 93 patients included in the study, there were 27 cases with preinvasive lesions (38 GGNs) and 66 cases with MIA (73 GGNs). No statistically significant difference was observed in terms of the gender, age and number of lesions between the two groups. There were significant differences (P<0.05) in the size of lesion, size of solid portion, content of solid portion, and morphological characteristics of the lesion edge between preinvasive lesions and MIA. ROC curve analysis showed that the optimal cut-off value of lesion size for differentiating preinvasive lesions from MIA was 13.0 mm (sensitivity, 83.0%; specificity, 80.0%), and that of solid portion size was 2.0 mm (sensitivity, 90.0%; specificity, 97.0%) and that of solid proportion was 12.0% (sensitivity, 88.0%; specificity, 97.0%). The analysis of CT morphological features showed that there were significant differences in the terms of lesion nature (pGGO, mGGO), presence or absence of lobulated sign and spiculated sign (P<0.05) between preinvasive lesions and MIA, but there were no significant differences in terms of the lesion edge, the presence or absence of vacuole sign, bubble lucency and pleural retraction (P>0.05).

CONCLUSIONSPreinvasive lesions can be accurately distinguished from MIA by the size of lesion, size of solid portion,solid proportion and morphological characteristics of the lesion edge. The size of lesion, size of solid portion, content of solid proportion and morphological characteristics of the lesion edge are of significance in the differential diagnosis of preinvasive lesions and minimally invasive adenocarcinoma of the lung.

Adenocarcinoma ; diagnostic imaging ; pathology ; Diagnosis, Differential ; Humans ; Lung Neoplasms ; diagnostic imaging ; pathology ; Multidetector Computed Tomography ; Neoplasm Invasiveness ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity

Objective To explore the correlation between 18F-FLT SUVmax and intratumoral microvessel density (MVD) in NSCLC patients.Methods From January 2008 to December 2010,68 patients (48males and 20 females; age ranging from 36 to 84 years) with NSCLC underwent 18F-FLT PET/CT followed by surgery within two weeks.Tumor proliferation was evaluated in terms of Ki67 labeling index (LI) with SP.MVD was determined using anti-CD31 mAb (CD31-MVD),anti-CD34 mAb (CD34-MVD) and anti-CD105 mAb (CD105-MVD) for each resected tumor.Linear correlation analysis was used to analyze data.Results The mean values of CD31-MVD,CD34-MVD and CD105-MVD were 159.6,166.1,and 38.0 per view field,respectively.Tumor SUVmax was 4.1±2.9,and Ki67 LI was (37.0± 14.5) ％,both of which had significantly correlations with CD105-MVD (r=0.550,0.633 ; both P＜0.05),but there was no significant relationship between SUVmax and CD31-MVD,CD34-MVD (r=0.228,0.235; both P＞0.05).Conclusion 18F-FLT PET/CT imaging has a positive relationship with CD105-MVD of NSCLC,and it could reflect the ability of tumor angiogenesis.

Objective The aim of this study was to retrospectively investigate the multi?detector computed tomography ( MDCT ) features of preinvasive lesions and minimally invasive adenocarcinoma (MIA) appearing as ground?glass nodules ( GGNs), and to analyze their significance in differential diagnosis. Methods The pathological data and MDCT images of 111 GGNs in 93 patients were reviewed and analyzed retrospectively, to identify the differentiating CT features between preinvasive lesions and MIA and to evaluate their differentiating accuracy. Results In the 93 patients included in the study, there were 27 cases with preinvasive lesions ( 38 GGNs) and 66 cases with MIA ( 73 GGNs) . No statistically significant difference was observed in terms of the gender, age and number of lesions between the two groups. There were significant differences (P<0.05) in the size of lesion, size of solid portion, content of solid portion, and morphological characteristics of the lesion edge between preinvasive lesions and MIA. ROC curve analysis showed that the optimal cut?off value of lesion size for differentiating preinvasive lesions from MIA was 13. 0 mm ( sensitivity, 83. 0%; specificity, 80. 0%) , and that of solid portion size was 2. 0 mm ( sensitivity, 90. 0%; specificity, 97. 0%) and that of solid proportion was 12. 0% ( sensitivity, 88. 0%;specificity, 97.0%) . The analysis of CT morphological features showed that there were significant differences in the terms of lesion nature (pGGO, mGGO), presence or absence of lobulated sign and spiculated sign ( P<0.05) between preinvasive lesions and MIA, but there were no significant differences in terms of the lesion edge, the presence or absence of vacuole sign, bubble lucency and pleural retraction ( P>0. 05 ) . Conclusions Preinvasive lesions can be accurately distinguished from MIA by the size of lesion, size of solid portion,solid proportion and morphological characteristics of the lesion edge. The size of lesion, size of solid portion, content of solid proportion and morphological characteristics of the lesion edge are of significance in the differential diagnosis of preinvasive lesions and minimally invasive adenocarcinoma of the lung.

Objective The aim of this study was to retrospectively investigate the multi?detector computed tomography ( MDCT ) features of preinvasive lesions and minimally invasive adenocarcinoma (MIA) appearing as ground?glass nodules ( GGNs), and to analyze their significance in differential diagnosis. Methods The pathological data and MDCT images of 111 GGNs in 93 patients were reviewed and analyzed retrospectively, to identify the differentiating CT features between preinvasive lesions and MIA and to evaluate their differentiating accuracy. Results In the 93 patients included in the study, there were 27 cases with preinvasive lesions ( 38 GGNs) and 66 cases with MIA ( 73 GGNs) . No statistically significant difference was observed in terms of the gender, age and number of lesions between the two groups. There were significant differences (P<0.05) in the size of lesion, size of solid portion, content of solid portion, and morphological characteristics of the lesion edge between preinvasive lesions and MIA. ROC curve analysis showed that the optimal cut?off value of lesion size for differentiating preinvasive lesions from MIA was 13. 0 mm ( sensitivity, 83. 0%; specificity, 80. 0%) , and that of solid portion size was 2. 0 mm ( sensitivity, 90. 0%; specificity, 97. 0%) and that of solid proportion was 12. 0% ( sensitivity, 88. 0%;specificity, 97.0%) . The analysis of CT morphological features showed that there were significant differences in the terms of lesion nature (pGGO, mGGO), presence or absence of lobulated sign and spiculated sign ( P<0.05) between preinvasive lesions and MIA, but there were no significant differences in terms of the lesion edge, the presence or absence of vacuole sign, bubble lucency and pleural retraction ( P>0. 05 ) . Conclusions Preinvasive lesions can be accurately distinguished from MIA by the size of lesion, size of solid portion,solid proportion and morphological characteristics of the lesion edge. The size of lesion, size of solid portion, content of solid proportion and morphological characteristics of the lesion edge are of significance in the differential diagnosis of preinvasive lesions and minimally invasive adenocarcinoma of the lung.