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Yanqing Ma,1 Xiren Xu,1 Peipei Pang,2 Yang Wen1 1Department of Radiology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310000, People’s Republic of China; 2Department of Pharmaceuticals Diagnosis, GE Healthcare, Hangzhou, 310000, People’s Republic of ChinaCorrespondence: Yanqing MaDepartment of Radiology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310000, People’s Republic of ChinaEmail 704180026@qq.comObjective: This study aimed to evaluate the role of tumor and mini-peritumor in the context of CT-based radiomics analysis to differentiate fat-poor angiomyolipoma (fp-AML) from clear cell renal cell carcinoma (ccRCC).Methods: A total of 58 fp-AMLs and 172 ccRCCs were enrolled. The volume of interest (VOI) was manually delineated in the standardized CT images and radiomics features were automatically calculated with software. After methods of feature selection, the CT-based logistic models including tumoral model (Ra-tumor), mini-peritumoral model (Ra-peritumor), perirenal model (Ra-Pr), perifat model (Ra-Pf), and tumoral+perirenal model (Ra-tumor+Pr) were constructed. The area under curves (AUCs) were calculated by DeLong test to evaluate the efficiency of logistic models.Results: The AUCs of Ra-peritumor of nephrographic phase (NP) were slightly higher than those of corticomedullary phase (CMP). Furthermore, the Ra-Pr showed significant higher efficiency than the Ra-Pf, and relative more optimal radiomics features were selected in the Ra-Pr than Ra-Pf. The Ra-tumor+Pr combined tumoral and perirenal radiomics analysis was of most significant in distinction compared with Ra-tumor and Ra-peritumor.Conclusion: The validity of NP to differentiate fp-AML from ccRCC was slightly higher than that of CMP. To the NP analysis, the Ra-Pr was superior to the Ra-Pf in distinction, and the lesions invaded to the perirenal tissue more severely than to the perifat tissue. It is important to the individual therapeutic surgeries according to the different lesion location. The pooled tumoral and perirenal radiomics analysis was the most promising approach in distinguishing fp-AML and ccRCC.Keywords: computed tomography, angiomyolipoma, clear cell renal cell carcinoma, peritumor, radiomics

Abstract Objective Many investigation have sought to identify therapeutic targets and treatment strategies for skin cutaneous melanoma (SKCM). Numb, an endocytic adaptor protein, is known to act as a tumor suppressor in various human cancers. However, the roles of Numb and its homolog NumbL in immune microenvironment, and their effect on melanoma remain largely unexplored. Methods We analyzed the expression levels of Numb and NumbL, as well as immune signatures of SKCM patients by UCSCXenaShiny v1 database. We also constructed animal model using Numb and NumbL conditional knockout (cKO) mice. Distribution analysis of immune cells in tumors was performed by flow cytometry and pathology staining. Results Numb and NumbL were found to be consistently expressed at low levels in SKCM patients. In addition, alterations in tumor immune microenvironment were identified. The CD8+ T, CD19+ B, and NK1.1+ CD49+ cells were decreased in tumors of Numb and NumbL cKO mice, confirming previous bioinformatics analysis of immune signatures. Additionally, we observed CD68+ macrophages to be increased as judged by tumor pathology staining. Conclusion Numb and NumbL were found to inhibit melanoma cell growth by modulating immune cell activity. These results suggested that Numb and NumbL may be potential therapeutic targets for SKCM patient immunotherapy.

Abstract Background and Purpose Early detection of non‐response to neoadjuvant chemoradiotherapy (nCRT) for locally advanced colorectal cancer (LARC) remains challenging. We aimed to assess whether pretreatment radiotherapy planning computed tomography (CT) radiomics could distinguish the patients with no response or no downstaging after nCRT from those with response and downstaging after nCRT. Materials and Methods Patients with LARC who were treated with nCRT were retrospectively enrolled between March 2009 and March 2019. Traditional radiological characteristics were analyzed by visual inspection and radiomic features were analyzed through computational methods from the pretreatment radiotherapy planning CT images. Differentiation models were constructed using radiomic methods and clinicopathological characteristics for predicting non‐response to nCRT. Model performance was assessed for classification efficiency, calibration, discrimination, and clinical application. Results This study enrolled a total of 215 patients, including 151 patients in the training cohort (50 non‐responders and 101 responders) and 64 patients in the validation cohort (21 non‐responders and 43 responders). For predicting non‐response, the model constructed with an ensemble machine learning method had higher performance with area under the curve (AUC) values of 0.92 and 0.89 as compared to the model constructed with the logistic regression method (AUC: 0.72 and 0.71 for the training and validation cohorts, respectively). Both decision curve and calibration curve analyses confirmed that the ensemble machine learning model had higher prediction performance. Conclusion Pretreatment CT radiomics achieved satisfying performance in predicting non‐response to nCRT and could be helpful to assist in treatment planning for patients with LARC.

Abstract Immunotherapy, especially immune checkpoint inhibitors (ICIs), has revolutionized the treatment of many types of cancer, particularly advanced-stage cancers. Nevertheless, although a subset of patients experiences dramatic and long-term disease regression in response to ICIs, most patients do not benefit from these treatments. Some may even experience cancer progression. Immune escape by tumor cells may be a key reason for this low response rate. N 6-methyladenosine (m6A) is the most common type of RNA methylation and has been recognized as a critical regulator of tumors and the immune system. Therefore, m6A modification and related regulators are promising targets for improving the efficacy of tumor immunotherapy. However, the association between m6A modification and tumor immune escape (TIE) has not been comprehensively summarized. Therefore, this review summarizes the existing knowledge regarding m6A modifications involved in TIE and their potential mechanisms of action. Moreover, we provide an overview of currently available agents targeting m6A regulators that have been tested for their elevated effects on TIE. This review establishes the association between m6A modifications and TIE and provides new insights and strategies for maximizing the efficacy of immunotherapy by specifically targeting m6A modifications involved in TIE.

Abstract Objective Whether preoperative serum carbohydrate antigen 19–9 (CA19-9) is an independent prognostic factor and there are interactions of serum CA19-9 with carcinoembryonic antigen (CEA) on the risk of recurrence in colorectal cancer (CRC) patients are still not clarified. Methods Consecutive patients with CRC who underwent curative resection for stage II-III colorectal adenocarcinoma at five hospitals were collected. Based on Cox models, associations of preoperative CA19-9 with recurrence-free survival (RFS) and overall survival (OS) were evaluated in patients with or without elevated CEA, and interactions between CEA and CA19-9 were also calculated. Restricted cubic spline (RCS) curves were used to evaluate the associations between preoperative CA19-9 and CRC outcomes on a continuous scale. Results A total of 5048 patients (3029 [60.0%] men; median [interquartile range, IQR] age, 61.0 [51.0, 68.0] years; median [IQR] follow-up duration 46.8 [36.5–62.4] months) were included. The risk of recurrence increased with the elevated level of preoperative CA19-9, with the slope steeper in patients with normal CEA than those with elevated CEA. Worse RFS was observed for elevated preoperative CA19-9 (> 37 U/mL) (n = 738) versus normal preoperative CA19-9 (≤ 37 U/mL) (n = 4310) (3-year RFS rate: 59.4% versus 78.0%; unadjusted hazard ratio [HR]: 2.02; 95% confidence interval [CI]:1.79 to 2.28), and significant interaction was found between CA19-9 and CEA (P for interaction = 0.001). Increased risk and interaction with CEA were also observed for OS. In the Cox multivariable analysis, elevated CA19-9 was associated with shorter RFS and OS regardless of preoperative CEA level, even after adjustment for other prognostic factors (HR: 2.08, 95% CI:1.75 to 2.47; HR: 2.25, 95% CI:1.80 to 2.81). Subgroup analyses and sensitivity analyses yielded largely similar results. These associations were maintained in patients with stage II disease (n = 2724). Conclusions Preoperative CA19-9 is an independent prognostic factor in CRC patients. Preoperative CA19-9 can be clinically used as a routine biomarker for CRC patients, especially with preoperative normal serum CEA.

Abstract Background The outcome of patients with T4 esophageal squamous cell carcinoma (ESCC) is extremely poor. Two distinct therapeutic options are currently available for T4 esophageal cancers: neochemoradiotherapy followed by surgery (CRT-S) and definitive chemoradiotherapy (D-CRT). This study aimed to investigate the clinicopathologic characteristics of T4 ESCC in Chinese patients and compare the survival between the two therapeutic options. Methods We retrospectively analyzed 125 patients with clinically unresectable T4 ESCC in Tianjin Medical University Cancer Institute and Hospital from January 2010 to December 2020. Overall survival (OS), progression-free survival (PFS) and associated factors were analyzed. Results A total of 106 of 125 T4 ESCC patients were downstaged of the tumor by neoadjuvant CRT. Among 106 patients, 32 patients underwent CRT-S, and 74 patients underwent D-CRT. Patients in the CRT-S group had a higher OS (20.4 months vs. un-reached median OS, p = 0.037) and PFS (8.6 months vs. 21.0 months, p = 0.008) than those in the D-CRT group. In multivariate analysis, treatment was an independent predictor of PFS. After propensity score matching (PSM), 50 patients (CRT-S = 25; D-CRT = 25) were matched. Among these 50 patients, patients in the CRT-S group had a higher OS (15.6 months vs. un-reached median OS, p = 0.025) and PFS (7.2 months vs. 18.8 months, p = 0.026) than those in the D-CRT group. In multivariate analysis, treatment was an independent predictor for PFS. Conclusion We demonstrated that CRT-S was superior to D-CRT for T4 ESCC patients who were downstaged by neo-CRT with respect to longer OS and PFS. Randomized controlled trials involving large population samples are needed to define the standard treatment for T4 ESCC.

Background and purpose: The Shanghai Municipal Center for Disease Control and Prevention provides annual updates on cancer occurrence and trends in Shanghai. This study aimed to investigate the cervical cancer incidence and mortality in 2016 and their trends from 2002 to 2016 in Shanghai. Methods: Data of new cervical cancer diagnoses and deaths from 2002 to 2016 were obtained from the population-based cancer registry and Vital Statistics System of Shanghai Municipal Center for Disease Control and Prevention. Cervical cancer incidence and mortality stratified by year of diagnosis or death, and age group were analyzed. Number, proportion, crude rate, age-specific rate, age-standardized rate and others were calculated. The number, proportion and rates of common cancers in different groups were also calculated. Trends in number, age-standardized rates and age-specific rates of incidence and death were estimated. Trends in age-standardized rates of incidence and death were estimated by Joinpoint analysis and characterized by the annual percent change (APC). The cases and proportion of selected diagnostic characteristics in different periods of diagnosis years grouped were also calculated. Segi’s 1960 world standard population was used for calculating age-standardized rates of incidence and mortality. Results: The new cervical cancer cases and deaths were 987 and 267 in Shanghai in 2016. The crude rate of incidence was 13.53/105, and the age-standardized rate of incidence was 8.26/105. The crude rate of mortality was 3.66/105, and the age-standardized rate of mortality was 1.87/105. The age-specific number and rate of incidence reached the peak in the age group of 55-59 years and 45-49 years respectively, while those of mortality reached the peak in the age group of 50-54 years and 80-84 years respectively. The standardized incidence rate of cervical cancer increased by an average annual growth of 12.51% from 2002 to 2010 and 3.12% per year from 2010 to 2016 in Shanghai. The standardized mortality rate increased by 4.52% per year from 2002 to 2016. The major histopathological type of cervical cancer was squamous cell carcinoma. The proportions of morphological verification and stage Ⅰwere increasing. Conclusions: In Shanghai, the incidence and mortality of cervical cancer were at a lower level of the world, but they were increasing. The current status and trends reflect Shanghai permanent population changes in risk factors, screening test use, diagnostic practices and treatment advances. Improvement of the surveillance and research on cervical cancer will help to promote more efficient control and prevention strategies and decrease cancer burden.

Abstract Background Cadherin-23 (CDH23) plays an important role in intercellular adhesion and is involved in the progression of several types of cancer. However, the biological functions and effect of CDH23 expression on the prognosis of patients with acute myeloid leukemia (AML) are unexplored. Herein, we aim to characterize the role and molecular functions of CDH23 in AML. Methods We downloaded the transcriptomic profiles and clinical data from the Cancer Genome Atlas and Beat AML trial. The expression level of CDH23 was assessed using Gene Expression Profiling Interactive Analysis (GEPIA). Kaplan-Meier survival analysis was used to assess prognostic value of CDH23. Correlation and biological function analyses were performed using LinkedOmics and GeneMANIA. Relationship of CDH23 with immune infiltration level was determined using Tumor Immune Estimation Resource (TIMER). Results We found that the CDH23 expression was aberrantly upregulated in patients with AML and could be used as an independent risk factor of overall survival using Cox multivariate analysis. Notably, we observed a negative correlation between CDH23 expression and immune cell infiltration abundance by calculating the immune and stromal scores. In addition, functional enrichment analysis established that CDH23 plays a crucial role in tumor immunity. Conclusions Our findings indicate that upregulated CDH23 expression corresponds to decreased overall survival of patients with AML. CDH23 may be involved in mediating tumor immune environment, and this highlights the potential of CDH23 as a therapeutic target in AML.

Abstract Background Recently the role of microRNAs has been explored immensely as novel regulators and potential biomarkers in several cancers. MiR-509-3p is one such miRNA that has been observed to show a mixed expression in different cancers, while it’s expression and clinical relevance in colorectal cancer (CRC) has not yet been characterized. Methods We used quantitative PCR to evaluate the expression of miR-509-3p in fresh-frozen CRC tumor tissues and the corresponding tumor-adjacent normal (NAT) tissues from 103 patients. Subsequently, functional studies were performed to further interpret the role of the miRNA in CRC. Results MiR-509-3p was found to be overexpressed in CRC tissues in nearly 80% of cases and was associated with an aggressive disease presentation. Notably, a higher expression of the miRNA promoted cell proliferation, migration, and invasion of CRC cells in in vitro and in vivo models. Mechanistically, we confirmed that miR-509-3p directly binds the 3’UTR of the tumor suppressor PHLPP2 and inhibits its expression. Furthermore, within the previous 103 clinical tissue specimens, we observed an overexpression of miR-509-3p within the NAT tissue of patients associated with a poor disease prognosis. Using multivariate analysis, it was observed that the expression of miR-509-3p within the NAT tissue was an independent predictor of prognosis in CRC. At the cellular level, through indirect coculture experiments, miR-509-3p was observed to regulate the proliferative, migratory, and invasive behavior of normal colon cells. Conclusion MiR-509-3p strongly contributes to the development and progression of CRC and can potentially function as a prognostic biomarker in the disease.

Purpose: To establish a model for assessing the overall survival (OS) of the hepatocellular carcinoma (HCC) patients after hepatectomy based on the clinical and radiomics features. Methods: This study recruited a total of 267 patients with HCC, which were randomly divided into the training (N = 188) and validation (N = 79) cohorts. In the training cohort, radiomic features were selected with the intra-reader and inter-reader correlation coefficient (ICC), Spearman's correlation coefficient, and the least absolute shrinkage and selection operator (LASSO). The radiomics signatures were built by COX regression analysis and compared the predictive potential in the different phases (arterial, portal, and double-phase) and regions of interest (tumor, peritumor 3 mm, peritumor 5 mm). A clinical-radiomics model (CR model) was established by combining the radiomics signatures and clinical risk factors. The validation cohort was used to validate the proposed models. Results: A total of 267 patients 86 (45.74%) and 37 (46.84%) patients died in the training and validation cohorts, respectively. Among all the radiomics signatures, those based on the tumor and peritumor (5 mm) (AP-TP5-Signature) showed the best prognostic potential (training cohort 1–3 years AUC:0.774–0.837; validation cohort 1–3 years AUC:0.754–0.810). The CR model showed better discrimination, calibration, and clinical applicability as compared to the clinical model and radiomics features. In addition, the CR model could perform risk-stratification and also allowed for significant discrimination between the Kaplan-Meier curves in most of the subgroups. Conclusions: The CR model could predict the OS of the HCC patients after hepatectomy.

Background: The surrogacy of progression-free survival (PFS) for overall survival (OS) in esophageal squamous cell carcinoma (ESCC) remains unelucidated. This study aimed to determine the validity of PFS as a surrogate endpoint for OS in ESCC patients treated with definitive radiotherapy or definitive chemoradiotherapy (dRT/dCRT), as well as characterize the prognostic factors and survival of such patients. Methods: A total of 3662 patients from 10 cancer centers were enrolled. One-, 2-, and 3-year PFS (PFS12, PFS24, and PSF36, respectively) were used as time points for analysis. At each time point, ESCC-specific mortality and OS were characterized using competing risk and conditional survival models, while correlation between PFS and OS was evaluated by linear regression. Results: At PFS12, PFS24, and PFS36, a progressive decrease in 5-year ESCC-specific mortality (35.2%–13.4%) and increase in 5-year OS (46.6%–62.9%) were observed. Regardless, the OS of patients remained markedly lower than those of the age- and sex-matched Chinese general population. TNM stage remained a significant prognostic factor at PFS36. Strong correlation was found between 3-year PFS and 5-year OS, which was further externally validated. Conclusions: Three-year PFS may act as a potential surrogate endpoint for 5-year OS. TNM stage was considered a significant prognostic factor for OS, and may represent the optimal prognostic tool to guide clinical decision-making and post-treatment follow-up.

BackgroundCommensal microbiota have been proven to colonize the mammary gland, but whether their composition is altered in patients with breast cancer (BC) remains elusive. This study intends to explore the breast microbiome differences between benign and malignant diseases and to investigate the impact of neoadjuvant chemotherapy (NAC) on the breast microbiota in patients with BC.MethodsBreast normal adipose tissues (NATs) were collected from 79 patients with BC and 15 controls between July 2019 and November 2021. The BC group consisted of 29 patients who had received NAC and 50 who were non-NAC patients. Participants diagnosed with benign breast disease were recruited as controls. 16S rRNA gene sequencing was used to analyze the bacterial diversity of NATs.ResultsThe community structure of the NAT microbiome was significantly different between the BC and control groups. Proteobacteria decreased (47.40% versus 39.74%), whereas Firmicutes increased (15.71% versus 25.33%) in patients with BC when compared with that in control tissues. Nine genera were enriched in BC NATs, and four genera levels increased in the control group. The associations between differential bacterial genera and breast tumor grade were calculated by Spearman’s correlation. The results showed that tumor grade was positively associated with the relative abundance of Streptococcus and negatively related to Vibrio, Pseudoalteromonas, RB41, and Photobacterium. Moreover, menopause was associated with the microbiota composition change of non-NAC BC patients and related to the significant reduction in the abundance level of Pseudoalteromonas, Veillonella, and Alcaligenes. In addition, NAC was related to the beta diversity of patients with BC and associated with the decrease of Clostridium_sensu_stricto_7 and Clostridium_sensu_stricto_2 in postmenopausal patients. Of note, Tax4Fun functional prediction analysis revealed that the metabolic state was more exuberant in the BC group with upregulating of multiple metabolism-related pathways.ConclusionOur results offer new insight into the relationship between NAC and breast microbiota and help to better characterize the breast microbial dysbiosis that occurs in patients with BC. Further epidemiological studies with larger sample size and well-designed animal experiments are required to elucidate the role of breast microbiota in the therapeutic outcome of BC.

Multiple neuroendocrine tumors (M-NETs) are rare in the rectum and there is no consensus on their characteristics and treatments. Here, we report 15 cases of rectal M-NETs and review the previous literature. We discuss the clinical characteristics, endoscopic features and pathological features of rectal M-NETs, aiming to analyze the treatments and follow-up strategies in combination with these characteristics. We retrospectively reviewed and analyzed the data of 15 patients with rectal M-NETs who were diagnosed and treated at Beijing Friendship Hospital, Capital Medical University. Their clinical data, endoscopic findings, pathological features and treatments were analyzed. Follow-up evaluations and literature review were performed. In all, 14 male (93.3%) and 1 female (6.7%) were recruited. The average age at diagnosis was 55.7 years. The clinical manifestations include asymptomatic in 9 patients (60.0%), defecation habits changes in 2 patients (13.3%), anal distension in 2 patients (13.3%), and abdominal distension in 2 patient (13.3%). The largest tumor diameter ≤10mm was found in 13 patients (86.7%) and >10mm in 2 patients (13.3%). All of the lesions originated from the mucous or submucosa layer. WHO grades were all NET G1. The number of tumors diagnosed by pathology in 13 patients was consistent with that observed by endoscopy, while more lesions were observed by pathology than endoscopy in two patients. Lymph node metastasis occurred in 1 patient (6.7%), and vascular or lymphatic invasion occurred in 9 patients (60.0%). Among the 13 patients with the largest tumor diameter being ≤10mm, lymphovascular invasion occurred in 8 patients (61.5%). And among the 2 patients with the largest tumor diameter of >10mm, lymphovascular invasion occurred in 1 patient (50.0%). 14 patients underwent endoscopic resection and 1 underwent surgical excision. Postoperative follow-up was achieved in 13 patients and no recurrence or metastasis was found. The true number of rectal M-NETs may be more than seen under endoscopy. Rectal M-NETs is associated with a high risk of metastasis; therefore, treatment and surveillance strategies should be more radical than single lesion.

Objectives(1) To assess the methodological quality and risk of bias of radiomics studies investigating the diagnostic performance in adrenal masses and (2) to determine the potential diagnostic value of radiomics in adrenal tumors by quantitative analysis.MethodsPubMed, Embase, Web of Science, and Cochrane Library databases were searched for eligible literature. Methodological quality and risk of bias in the included studies were assessed by the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) and Radiomics Quality Score (RQS). The diagnostic performance was evaluated by pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC). Spearman’s correlation coefficient and subgroup analysis were used to investigate the cause of heterogeneity. Publication bias was examined using the Deeks’ funnel plot.ResultsTwenty-eight studies investigating the diagnostic performance of radiomics in adrenal tumors were identified, with a total of 3579 samples. The average RQS was 5.11 (14.2% of total) with an acceptable inter-rater agreement (ICC 0.94, 95% CI 0.93–0.95). The risk of bias was moderate according to the result of QUADAS-2. Nine studies investigating the use of CT-based radiomics in differentiating malignant from benign adrenal tumors were included in the quantitative analysis. The pooled sensitivity, specificity, DOR and AUC with 95% confidence intervals were 0.80 (0.68-0.88), 0.83 (0.73-0.90), 19.06 (7.87-46.19) and 0.88 (0.85–0.91), respectively. There was significant heterogeneity among the included studies but no threshold effect in the meta-analysis. The result of subgroup analysis demonstrated that radiomics based on unenhanced and contrast-enhanced CT possessed higher diagnostic performance, and second-order or higher-order features could enhance the diagnostic sensitivity but also increase the false positive rate. No significant difference in diagnostic ability was observed between studies with machine learning and those without.ConclusionsThe methodological quality and risk of bias of studies investigating the diagnostic performance of radiomics in adrenal tumors should be further improved in the future. CT-based radiomics has the potential benefits in differentiating malignant from benign adrenal tumors. The heterogeneity between the included studies was a major limitation to obtaining more accurate conclusions.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/ CRD 42022331999 .

Castleman’s disease (CD) is a primary lymphoproliferative disorder of the lymph nodes with rare extra-nodal primary affection. Solid organ involvement is rare, and isolated liver involvement is extremely rare. Here we presented a case of a 59-year-old woman with a hepatic lesion accidentally found by ultrasound. The MRI result indicated primary liver malignancy or liver metastases. 18F-FDG PET/CT could not exclude hepatic malignant tumor due to its high metabolism. Finally, the hepatic CD was confirmed by postoperative pathology.

Chemo-radiotherapy (CRT) remains the main treatment modality for non-small-cell lung cancer (NSCLC). However, its clinical efficacy is largely limited by individual variations in radio-sensitivity and radiotherapy-associated toxicity. There is an urgent need to identify genetic determinants that can explain patients’ likelihood to develop recurrence and radiotherapy-associated toxicity following CRT. In this study, we performed comprehensive genomic profiling, using a 474-cancer- and radiotherapy-related gene panel, on pretreatment biopsy samples from patients with unresectable stage III NSCLCs who underwent definitive CRT. Patients’ baseline clinical characteristics and genomic features, including tumor genetic, genomic and molecular pathway alterations, as well as single nucleotide polymorphisms (SNPs), were correlated with progression-free survival (PFS), overall survival (OS), and radiotherapy-associated pneumonitis and/or esophagitis development after CRT. A total of 122 patients were enrolled between 2014 and 2019, with 84 (69%) squamous cell carcinomas and 38 (31%) adenocarcinomas. Genetic analysis confirmed the association between the KEAP1-NRF2 pathway gene alterations and unfavorable survival outcome, and revealed alterations in FGFR family genes, MET, PTEN, and NOTCH2 as potential novel and independent risk factors of poor post-CRT survival. Combined analysis of such alterations led to improved stratification of the risk populations. In addition, patients with EGFR activating mutations or any oncogenic driver mutations exhibited improved OS. On the other hand, we also identified genetic markers in relation to radiotherapy-associated thoracic toxicity. SNPs in the DNA repair-associated XRCC5 (rs3835) and XRCC1 (rs25487) were associated with an increased risk of high-grade esophagitis and pneumonitis respectively. MTHFR (rs1801133) and NQO1 (rs1800566) were additional risk alleles related to higher susceptibility to pneumonitis and esophagitis overall. Moreover, through their roles in genome integrity and replicative fidelity, somatic alterations in ZNF217 and POLD1 might also serve as risk predictors of high-grade pneumonitis and esophagitis. Taken together, leveraging targeted next-generating sequencing, we identified a set of novel clinically applicable biomarkers that might enable prediction of survival outcomes and risk of radiotherapy-associated thoracic toxicities. Our findings highlight the value of pre-treatment genetic testing to better inform CRT outcomes and clinical actions in stage III unresectable NSCLCs.

BackgroundHepatocellular carcinoma (HCC) is a primary malignancy of the liver with high prevalence worldwide and poor prognosis. It has been verified that elongation of very-long-chain fatty acids gene family (ELOVLs), a group of genes that responsible for elongation of saturated and polyunsaturated fatty acids, participate in the pathogenesis and development of multiplex disease including cancers. However, the functions and prognosis of ELOVLs in HCC are still indistinguishable.MethodsFirst, we searched the mRNA expression and survival data of ELOVLs in patients with HCC via the data of The Cancer Genome Atlas (TCGA). The prognosis value of ELOVLs on HCC was assessed by Kaplan–Meier plotter and Cox regression analysis. reverse transcription quantitative- polymerase chain reaction (RT-qPCR), Western blot (WB), and immunohistochemistry were applied to assess the specific mRNA and protein expression of ELOVLs in HCC clinical specimens of our cohort. Then, the functional enrichment of ELOVL1 especially the pathways relating to the immune was conducted utilizing the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) analysis. Additionally, TIMER, CIBERSOR, and tumor immune dysfunction and exclusion (TIDE) were employed to evaluate the relationship between ELOVL1 and immune responses. Last, the correlation of ELOVL1 with genome heterogeneity [microsatellite instability (MSI), tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), homologous recombination deficiency (HRD), purity, ploidy, loss of heterozygosity (LOH), and neoantigens] and mutational landscape were also evaluated basing on the date in TCGA.ResultsSignificant expression alteration was observed in ELOVLs family at the pan-cancer level. In liver cancer, ELOVL1 and ELOVL3 were strongly associated with poor prognosis of HCC by survival analysis and differential expression analysis. Immunohistochemistry microarray, WB, and RT-qPCR confirmed that ELOVL1 but not ELOVL3 played an important role in HCC. Mechanistically, functional network analysis revealed that ELOVL1 might be involved in the immune response. ELOVL1 could affect immune cell infiltration and immune checkpoint markers such as PD-1 and CTLA4 in HCC. Meanwhile, high expression of ELOVL1 would be insensitive to immunotherapy. Correlation analysis of immunotherapy markers showed that ELOVL1 has been associated with MSI, TMB, and oncogene mutations such as TP53.ConclusionELOVLs play distinct prognostic value in HCC. ELOVL1 could predict the poor prognosis and might be a potential indicator of immunotherapy efficacy in HCC patients.

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumour typically affecting the skin of fair-skinned or immunosuppressed, though it can affect the oral mucosa. We report the fourth documented case of MCC of the tongue in an 87-year-old male presenting with a cervical mass causing odynophagia and dysphagia. The diagnosis was confirmed through core biopsy histopathology and immunohistochemical analysis positive for CK20, synaptophysin and chromogranin. In situ hybridisation for human papillomavirus types 16 and 18 was negative, excluding HPV-driven oropharyngeal squamous cell carcinoma. Non-operative management with intensity-modulated radiotherapy and avelumab immunotherapy was commenced, inducing a complete metabolic response of the primary lesion. Thirty-three months after diagnosis, 31 months after completing initial radiotherapy, the patient is clinically well with no residual disease. Despite a dearth of documented cases, our protocol suggests that novel techniques for cutaneous MCC management with immunotherapy combined with our improved knowledge of MCC radiobiology may be successfully applied to managing locally advanced oral MCC, potentially shifting the treatment paradigm from upfront surgery toward targeted oncotherapy.

Cancer is a major public health problem worldwide. Studies on oncogenes and tumor-targeted therapies have become an important part of cancer treatment development. In this review, we summarize and systematically introduce the gene enhancer of rudimentary homolog (ERH), which encodes a highly conserved small molecule protein. ERH mainly exists as a protein partner in human cells. It is involved in pyrimidine metabolism and protein complexes, acts as a transcriptional repressor, and participates in cell cycle regulation. Moreover, it is involved in DNA damage repair, mRNA splicing, the process of microRNA hairpins as well as erythroid differentiation. There are many related studies on the role of ERH in cancer cells; however, there are none on tumor-targeted therapeutic drugs or related therapies based on the expression of ERH. This study will provide possible directions for oncologists to further their research studies in this field.

BackgroundHepatocellular carcinoma (HCC) is one of the most lethal human tumors with extensive intratumor heterogeneity (ITH). Serine protease 3 (PRSS3) is an indispensable member of the trypsin family and has been implicated in the pathogenesis of several malignancies, including HCC. However, the paradoxical effects of PRSS3 on carcinogenesis due to an unclear molecular basis impede the utilization of its biomarker potential. We hereby explored the contribution of PRSS3 transcripts to tumor functional heterogeneity by systematically dissecting the expression of four known splice variants of PRSS3 (PRSS3-SVs, V1~V4) and their functional relevance to HCC.MethodsThe expression and DNA methylation of PRSS3 transcripts and their associated clinical relevance in HCC were analyzed using several publicly available datasets and validated using qPCR-based assays. Functional experiments were performed in gain- and loss-of-function cell models, in which PRSS3 transcript constructs were separately transfected after deleting PRSS3 expression by CRISPR/Cas9 editing.ResultsPRSS3 was aberrantly differentially expressed toward bipolarity from very low (PRSS3Low) to very high (PRSS3High) expression across HCC cell lines and tissues. This was attributable to the disruption of PRSS3-SVs, in which PRSS3-V2 and/or PRSS3-V1 were dominant transcripts leading to PRSS3 expression, whereas PRSS3-V3 and -V4 were rarely or minimally expressed. The expression of PRSS3-V2 or -V1 was inversely associated with site-specific CpG methylation at the PRSS3 promoter region that distinguished HCC cells and tissues phenotypically between hypermethylated low-expression (mPRSS3-SVLow) and hypomethylated high-expression (umPRSS3-SVHigh) groups. PRSS3-SVs displayed distinct functions from oncogenic PRSS3-V2 to tumor-suppressive PRSS3-V1, -V3 or PRSS3-V4 in HCC cells. Clinically, aberrant expression of PRSS3-SVs was translated into divergent relevance in patients with HCC, in which significant epigenetic downregulation of PRSS3-V2 was seen in early HCC and was associated with favorable patient outcome.ConclusionsThese results provide the first evidence for the transcriptional and functional characterization of PRSS3 transcripts in HCC. Aberrant expression of divergent PRSS3-SVs disrupted by site-specific CpG methylation may integrate the effects of oncogenic PRSS3-V2 and tumor-suppressive PRSS3-V1, resulting in the molecular diversity and functional plasticity of PRSS3 in HCC. Dysregulated expression of PRSS3-V2 by site-specific CpG methylation may have potential diagnostic value for patients with early HCC.

Although the link between sugar-sweetened beverages (SSB) and pancreatic cancer has been suggested for its insulin-stimulating connection, most epidemiological studies showed inconclusive relationship. Whether the result was limited by sample size is explored. This prospective study followed 491,929 adults, consisting of 235,427 men and 256,502 women (mean age: 39.9, standard deviation: 13.2), from a health surveillance program and there were 523 pancreatic cancer deaths between 1994 and 2017. The individual identification numbers of the cohort were matched with the National Death file for mortality, and Cox models were used to assess the risk. The amount of SSB intake was recorded based on the average consumption in the month before interview by a structured questionnaire. We classified the amount of SSB intake into 4 categories: 0–

Background and AimsChronic atrophic gastritis (CAG) is closely related to the development of gastric cancer. However, the diagnostic accuracy of white light endoscopy (WLE) biopsy for CAG is poor. The diagnostic role and efficacy of confocal laser endomicroscopy (CLE) in CAG missed under WLE biopsy remain unclear.MethodsThis study is a single-center prospective study that included 21 patients from 1,349 patients who underwent WLE and biopsy and whose WLE results confirmed CAG, but pathological results did not. Then, all these patients received CLE examination and underwent targeted biopsies and five-point standard biopsies. The sensitivity, specificity, and accuracy of CLE diagnosis and targeted biopsy were analyzed.ResultsThe pathological results of five-point standard biopsies in 21 patients confirmed CAG, and 17 patients (81.0%) were confirmed to have intestinal metaplasia (IM). According to the image diagnosis of CLE, there were 19 cases (90.5%) of CAG and 14 cases (66.7%) of IM among these 21 patients. According to the targeted biopsy of CLE, 17 cases (81.0%) of CAG and 14 cases (66.7%) of IM were diagnosed. There was no significant difference between CLE image diagnosis and five-point standard biopsies in terms of atrophy severity score (p = 0.927), IM severity score (p = 0.250), atrophy scope score (p = 0.781), and IM scope score (p = 0.195). For CAG, the sensitivity and accuracy of CLE image diagnosis were higher than those of CLE targeted biopsies (90.5% vs. 81.0%, p = 0.331), but for IM, the diagnosis was the same.ConclusionsCLE can improve the diagnosis rate of CAG and can increase the comprehensive assessment of the scope and severity of CAG.

Abstract Background Analysis of the risk factors associated with functional delayed gastric emptying after distal gastric cancer surgery to provide a basis for further reduction of the incidence of this complication. Methods Total of 1382 patients with distal gastric cancer from January 2016 to October 2018 were enrolled. Correlation analysis was performed in 53 patients with FDGE by logistic regression. Subgroup risk analysis was performed in 114 patients with preoperative pyloric obstruction. A Pearson Chi-square analysis was used to compare categorical variables between normal distribution groups. Meanwhile, a t test was used to compare continuous variables between groups. Odds ratio (OR) was used for comparison of the two groups, and it was summarized with its 95% confidence interval (CI) and p value using logistic regression. Result In multivariable analysis, age (OR 1.081, 95% CI, 1.047–1.117), BMI (OR 1.233, 95% CI, 1.116–1.363), preoperative pyloric obstruction (OR 3.831, 95% CI, 1.829–8.023), smaller volume of residual stomach (OR 1.838, 95% CI, 1.325–6.080), and anastomosis in greater curvature perpendicular (OR 3.385, 95% CI, 1.632–7.019) and in greater curvature parallel (OR 2.375, 95% CI, 0.963–5.861) were independent risk factors of FDGE. In the preoperative pyloric obstruction group, higher BMI (OR 1.309, 95% CI, 1.086–1.579) and preoperative obstruction time (OR 1.054, 95% CI, 1.003–1.108) were independent risk factors of FDGE and preoperative gastrointestinal decompression (OR 0.231, 95% CI, 0.068–0.785) was independent protective factor of FDGE. Conclusion Adequate gastrointestinal decompression should be performed before the operation to reduce the incidence of postoperative gastroparesis in patients with preoperative pyloric obstruction. We also could improve the surgical methods to reduce the occurrence of FDGE, such as controlling the size of the residual stomach, ensuring blood supply. Especially selecting an appropriate stapler and anastomosis during the anastomosis process, the occurrence of FDGE can be reduced.

Abstract Purpose Previous studies have provided evidence of the high expression of lactate dehydrogenase (LDH) in multiple solid tumors; however, its prognostic relationship with metastatic prostate cancer (mPCa) remains controversial. We performed a meta‐analysis to better understand the prognostic potential of LDH in mPCa. Methods In our investigation, we included PubMed, Embase, Web of Science, and Cochrane Library as web‐based resources, as well as studies published before January 2020 on the predictive value of LDH in mPCa. We independently screened the studies according to the inclusion and exclusion criteria, evaluated the quality of the literature, extracted the data, and used RevMan 5.3 and STATA12.0 software for analysis. Result From the 38 published studies, the records of 9813 patients with mPCa were included in this meta‐analysis. We observed that higher levels of LDH in patients with mPCa were significantly associated with poorer overall survival (OS) (HR = 2.17, 95% CI: 1.91‐2.47, P

Abstract Background Thyroid cancer (TC) is the most common endocrine malignancy; basigin (also known as BSG) plays a crucial role in tumor cell invasion, metastasis, and angiogenesis. This study was designed to identify the change of BSG expression in TC and its possible potential mechanism. Methods The BSG expression levels in TC were demonstrated using data collected from in-house immunohistochemical (IHC), RNA-sequencing (RNA-seq), microarrays, and literatures. Integrated analysis was performed to determined BSG expression levels in TC comprehensively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed with the integration of BSG co-expressed genes and differentially expressed genes (DEGs) in TC tissues to explore the potential mechanisms of BSG in TC. Results The protein expression level of BSG was significantly higher in TC cases based on the IHC experiments. In addition, the combined SMD for BSG expression was 0.39 (p < 0.0001), the diagnostic odds ratio was 3.69, and the AUC of the sROC curve was 0.6986 using 1182 TC cases and 437 non-cancerous cases from 17 independent datasets. Furthermore, BSG co-expressed genes tended to be enriched in gene terms of the extracellular matrix (ECM), cell adhesion, and cell-cell interactions. The expression levels of nine hub BSG co-expressed genes were markedly upregulated in TC cases. Conclusion BSG expression levels were closely correlated with the progression of TC and may affect the signals of the ECM, cell adhesion, and cell-cell interactions.

Abstract Background Chemoresistance is emerging as a major barrier to successful treatment in acute myeloid leukemia (AML), and evasion of apoptosis is among the fundamental underlying mechanisms. Therefore, unraveling molecular networks that drive this process constitutes an urgent unmet need. Herein, we aim to characterize the role and molecular mechanism of the tumor necrosis factor ɑ-induced protein 8 (TNFAIP8), a novel anti-apoptotic molecule, in AML chemoresistance. Methods The expression levels of TNFAIP8 were assessed in AML patients and cell lines by RT-qPCR and western blots. The transcriptional regulation of TNFAIP8 was analyzed with luciferase reporter assay and ChIP followed by RT-qPCR. Functional experiments were conducted to evaluate the effects of TNFAIP8 on apoptosis, drug sensitivity and proliferation of AML cells. Potential effects of TNFAIP8 on the activation of extracellular signal-regulated kinase (ERK) pathway were detected by western blots. CoIP and P21-activated kinase (PAK) pull-down assay were performed to ascertain the upstream target. The overall effects of TNFAIP8 on AML were examined in murine models. Results Upregulated TNFAIP8 expression was first confirmed in human AML patients and cell lines. E74 like ETS transcription factor 1 (ELF1) was then identified to contribute to its aberrant expression. Through manipulating TNFAIP8 expression, we described its role in protecting AML cells from apoptosis induced by chemotherapeutic agents and in promoting drug resistance. Notably, the leukemia-promoting action of TNFAIP8 was mediated by sustaining activity of the ERK signaling pathway, through an interaction with Rac family small GTPase 1 (Rac1). In addition, in vivo experiments confirmed that TNFAIP8 suppression lowered leukemia infiltration and improved survival. Conclusion Our data provide a molecular basis for the role of TNFAIP8 in chemoresistance and progression of AML and highlight the unique function of TNFAIP8 as an attractive therapeutic target.

Meng Pang,1 Chunyuan Li,1 Dong Zheng,1 Ying Wang,2 Jing Wang,1 Weilong Zhang,1 Fang Li,1 Hongmei Jing1 1Department of Hematology, Third Hospital of Peking University, Beijing, People’s Republic of China; 2Department of Immunology, Key Laboratory of Medical Immunology of Ministry of Health, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People’s Republic of ChinaCorrespondence: Fang Li; Hongmei Jing Email lifang19611962@163.com; hongmeijing@bjmu.edu.cnBackground: The presence of circulating plasma cells (cPCs) was associated with a worse prognosis in multiple myeloma patients. However, the underlying mechanisms involved in the migration and invasion of bone marrow myeloma cells (BMMCs) to cPCs remains unclear. Here, we investigate the possible factors related to hematogenous myeloma cell dissemination and potential regulatory mechanisms.Methods: BMMCs and cPCs of five extramedullary plasmacytoma (EMP) patients were selected for single cell RNA sequencing, We found that the expression level of sphingosine-1-phosphate receptor 2 (S1RP2) was lower in cPCs compared with that in BMMCs. Then, we investigated the effect of S1PR2 in cell migration and invasion through pharmacologic inhibition with a S1PR2-selective antagonist JTE-013 or knockdown of S1PR2 expression in MM cell line U266.Results: The results showed that S1PR2 inhibition with JTE-013 or S1PR2-shRNA significantly promoted cell migration and invasion in U266 cells. We measured the expression of invasion-related proteins by Western blot and found that knockdown of S1PR2 could reduce MMP-9 expression in U266 cells. Furthermore, we found NF-κB pathway may mediate the inhibition effects of S1PR2 on cell migration and invasion in MM cells.Conclusion: Our findings demonstrated that S1PR2 downregulation may contribute to the initial extramedullary translocation by promoting cell migration and invasion through NF-κB pathway activation.Keywords: multiple myeloma, extramedullary plasmacytoma, circulating plasma cells, NF-κB, S1PR2

Jun Li,1,* Donggen Jiang,1,* Qian Zhang,2,* Shubin Peng,3 Guolong Liao,1 Xiangwei Yang,1 Jiani Tang,1 Haiyun Xiong,1 Jun Pang1 1Department of Urology, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, People’s Republic of China; 2Department of Rehabilitation Medicine, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, People’s Republic of China; 3Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Pang; Haiyun XiongDepartment of Urology, Seventh Affiliated Hospital, Sun Yat-Sen University, 628 Zhenyuan Road, Shenzhen 518107, People’s Republic of ChinaTel +86-18802044177; +86-18922869986Email pangjun2@mail.sysu.edu.cn; xionghy7@mail.sysu.edu.cnObjective: Renal cell carcinoma (RCC) displays an increasing incidence and mortality rate worldwide in recent years. More and more evidence demonstrated microRNAs function as positive or negative regulatory factors in many cancers, while the role of miR-301a in RCC is still unclear.Material and Methods: The expression and clinical significance of miR-301a were assessed via bioinformatic software on open microarray datasets of the Cancer Genome Atlas (TCGA) and then confirmed by quantitative real-time PCR (qRT-PCR) in RCC cell lines. Loss of function assays were performed in RCC cell lines both in vitro and in vivo. Cell Counting Kit-8 (CCK-8), flow cytometry, luciferase reporter assays, Western blotting, and immunohistochemistry were employed to explore the mechanisms of the effect of miR-301a on RCC.Results: By analyzing RCC clinical specimens and cell lines, we found a uniform increased miR-301a in expression in comparison with normal renal tissue or normal human proximal tubule epithelial cell line (HK-2). In addition, miR-301a upregulation correlated advanced stage and poor prognosis of clear cell RCC (ccRCC). Anti-miR-301a could inhibit growth and cell cycle G1/S transition in RCC cell lines. Moreover, we found that PTEN was identified as a direct target of miR-301a that might partially interrupt miR-301a-induced G1/S transition. Importantly, nude-mouse models revealed that knockdown of miR-301a delayed tumor growth.Conclusion: These results indicate that miR-301a functions as a tumor-promoting miRNA through regulating PTEN expression, representing a novel therapeutic target for RCC.Keywords: miR-301a, PTEN, renal cell carcinoma, proliferation, G1/S transition

Objectives: Chemotherapy-induced nausea and vomiting (CINV) are distressing symptoms. This randomized study evaluated the antiemetic efficacies of standard antiemetic regimen with/without olanzapine. Patients and methods: Eligible patients were chemotherapy-naive Chinese breast cancer patients who were planned for (neo)adjuvant doxorubicin/cyclophosphamide. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomized to Olanzapine (with olanzapine) or Standard arms (without olanzapine). Patients filled in self-reported diaries and completed visual analogue scales for nausea, as well as Functional Living Index-Emesis questionnaires. Blood profiles including fasting glucose and lipids were monitored. Results: 120 patients were randomized. In Cycle 1 doxorubicin/cyclophosphamide, the Olanzapine arm had significantly higher rates of “Complete Response” than the Standard arm: 65.0% vs 38.3% in the overall period (p = 0.0035), 70.0% vs 51.7% in the acute period (p = 0.0397) and 92.9% vs 74.2% in the delayed period (p = 0.0254). Olanzapine arm also had significantly higher rates of “No significant nausea” and “No nausea” during all 3 time-frames and better QOL. Similar findings were also revealed throughout multiple cycles. Pre-study abnormalities in glucose and lipids occurred in 39.7% and 34.2% of the studied population respectively; there were no differences in these parameters between the two arms at end-of-study assessment. Conclusion: The addition of olanzapine to standard aprepitant-based antiemetic regimen provides clinically meaningful improvement in controlling CINV. This was associated with a positive impact on QOL and tolerable toxicity profiles among Chinese breast cancer patients receiving doxorubicin/cyclophosphamide chemotherapy. Further studies on metabolic profiles of breast cancer patients are warranted.

Abstract Purpose Removal of clipped nodes can improve sentinel node biopsy accuracy in breast cancer patients post neoadjuvant chemotherapy (NACT). However, the current methods of clipped node localization have limitations. We evaluated the feasibility of a novel clipped node localization and removal technique by preoperative skin marking of clipped nodes and removal by the Skin Mark clipped Axillary nodes Removal Technique (SMART), with the secondary aim of assessing the ultrasound visibility of the various clips in the axillary nodes after NACT. Methods Invasive breast cancer patients with histologically metastatic axillary nodes, going for NACT, and ≤3 sonographically abnormal axillary nodes were recruited. All abnormal nodes had clips inserted. Patients with M1 disease were excluded. Post‐NACT, patients underwent SMART and axillary lymph node dissection. Specimen radiography and pathological analyses were performed to confirm the clipped node presence. Success, complication rates of SMART, and ultrasound visibility of the various clips were assessed. Results Twenty‐five clipped nodes in 14 patients underwent SMART without complications. The UltraCor Twirl, hydroMARK, UltraClip Dual Trigger, and UltraClip were removed in 13/13 (100%), 7/9 (77.8%), 1/2 (50.0%), and 0/1 (0%), respectively (P = .0103) with UltraCor Twirl having the best ultrasound visibility and removal rate. Removal of three clipped nodes in the same patient (P = .0010) and deeply seated clipped nodes (P = .0167) were associated with SMART failure. Conclusion Skin Mark clipped Axillary nodes Removal Technique is feasible for removing clipped nodes post‐NACT, with 100% observed success rate, using the UltraCor Twirl marker in patients with

Heme oxygenase-1 (HO-1) has antiinflammatory and antioxidant properties and is deemed as a tissue protector. However, effects of HO-1 in prostate cancer remain in controversy. We evaluated the role of HO-1 in prostate carcinoma in vitro and in vivo.Overexpression of HO-1 did not affect prostate cell proliferation in the normal condition but enhanced cell proliferation under serum starvation. HO-1 overexpression enhanced cell invasion of PC-3 cells through epithelial–mesenchymal transition (EMT) induction, which was supported by increased Slug, N-cadherin, and vimentin expressions. In the xenograft animal study, HO-1 overexpression enhanced PC-3 cell tumor growth in vivo. HO-1 attenuated reactive oxygen species induced by H2O2 or pyocyanin treatment in PC-3 and DU145 cells. HO-1 further reduced PC-3 and DU145 cell apoptosis induced by H2O2 or serum starvation. Our results suggested that HO-1 was able to increase prostate carcinoma cell invasion in vitro and tumor growth in vivo. The EMT induction and antioxidant and antiapoptotic effects of HO-1 in the prostate carcinoma cells may be responsible for these findings.

Background. Immune checkpoint inhibitors are a promising therapeutic strategy for breast cancer (BRCA) patients. The tumor microenvironment (TME) can downregulate the immune response to cancer therapy. Our study is aimed at finding a TME-related biomarker to identify patients who might respond to immunotherapy. Method. We downloaded raw data from several databases including TCGA and MDACC to identify TME hub genes associated with overall survival (OS) and the progression-free interval (PFI) by WGCNA. Correlations between hub genes and either tumor-infiltrating immune cells or immune checkpoints were conducted by ssGSEA. Result. TME-related green and black modules were selected by WGCNA to further screen hub genes. Random forest and univariate and multivariate Cox regressions were applied to screen hub genes (MYO1G, TBC1D10C, SELPLG, and LRRC15) and construct a nomogram to predict the survival of BRCA patients. The C-index for the nomogram was 0.713. A DCA of the predictive model revealed that the net benefit of the nomogram was significantly higher than others and the calibration curve demonstrated a good performance by the nomogram. Only TBC1D10C was correlated with both OS and the PFI (both p values < 0.05). TBC1D10C also had a high positive association with tumor-infiltrating immune cells and common immune checkpoints (PD-1, CTLA-4, and TIGIT). Conclusion. We constructed a TME-related gene signature model to predict the survival probability of BRCA patients. We also identified a hub gene, TBC1D10C, which was correlated with both OS and the PFI and had a high positive association with tumor-infiltrating immune cells and common immune checkpoints. TBC1D10C may be a new biomarker to select patients who may benefit from immunotherapy.

Background. Colorectal cancer is one of the most common gastrointestinal malignancies globally. Necroptosis has been proved to play a role in the occurrence and development of the tumor, which makes it a new target for molecular therapy. However, the role of necroptosis in colorectal cancer remains unknown yet. Our study aims to build a prognostic signature of necroptosis-related lncRNAs (nrlncRNAs) to predict the outcomes of patients with colorectal cancer and facilitate in anticancer therapy. Method. We obtained RNA-seq and clinical data of colorectal adenocarcinoma from the TCGA database and got prognosis-related nrlncRNAs by univariate regression analysis. Then, we carried out the LASSO regression and multivariate regression analysis to build the prognostic signature, whose predictive ability was tested by the Kaplan-Meier as well as ROC curves and verified by the internal cohort. Moreover, we divided the cohort into 2 groups based on median of risk scores: high- and low-risk groups. By analyzing the difference in the tumor microenvironment, microsatellite instability, and tumor mutation burden between the two groups, we explored the potential chemotherapy and immunotherapy drugs. Results. We screened out 9 nrlncRNAs and built a prognostic signature based on them. With its good prognostic ability, the risk scores can act as an independent prognostic factor for patients with colorectal cancer. The overall survival rate of patients in high-risk group was significantly higher than the low-risk one. Furthermore, risk scores can also give us hints about the tumor microenvironment and facilitate in predicting the response to the CTLA-4 blocker treatment and other chemotherapeutic agents with potential efficacy such as cisplatin and staurosporine. Conclusions. In conclusion, our prognostic signature of necroptosis-related lncRNAs can facilitate in predicting the prognosis and response to the anticancer therapy of colorectal cancer patients.

Mengping Zhang,1,* Yong Bao,2,* Wei Chen,3,* Mengchao Wei,4 Hui Pang,5 Yu Feng Ren,2 Jie Mei,6 Sheng Ye,1 Shunjun Fu,7 Zhen Wei Peng1,61Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 2Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 3Department of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 4Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 5Department of Medical Records Management, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 6Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 7Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China*These authors contributed equally to this workPurpose: To explore a quantitative predictive model for the risk of chemotherapy-induced severe liver damage (CISLD).Materials and methods: In total, 3870 consecutive cancer patients initially treated with chemotherapy were retrospectively collected and randomly assigned to a training (n=2580) or internal validation (n=1290) set in a 2:1 ratio to construct and validate the model. Additional external validation was performed using another data set (n=413). A total of 486 patients were prospectively enrolled to assess the clinical significance of the model. CISLD was defined as grade ≥3 hepatotoxicity.Results: CISLD was found in 255 (9.9%), 128 (9.9%) and 36 (8.7%) patients in the training, internal and external validation sets, respectively. Serum triglyceride, body mass index and history of hypertension formed the basis of the score model. Patients could be stratified into low, intermediate and high-risk groups with 30% CISLD occurrence, respectively. This model displayed a concordance index (C-index) of 0.834 and was validated in both the internal (C-index, 0.830) and external (C-index, 0.817) sets. The incidence of CISLD was significantly reduced in those who received preventive hepatoprotective drugs compared to those who did not among patients assessed as the intermediate risk group (8.9% vs 17.5%, p=0.042) and the high risk group (15.6% vs 55.8%, p=0.043).Conclusions: The new score model can be used to accurately predict the risk of CISLD in cancer patients undergoing chemotherapy. Clinically, this can be translated into a reference tool for oncologists in the clinical decision-making process before chemotherapy to provide appropriate prevention and interventions for patients with a high risk of CISLD.Keywords: chemotherapy, liver damage, predictive model

Objective To investigate the dynamic characteristics, optimal development time and imaging mechanism of indocyanine green (ICG) in vitro near-infrared fluorescence imaging of subcutaneous xenograft tumor of prostate cancer in nude mice. Methods We selected 10 male SPF BALB/c-nu nude mice to construct PC3 tumor-bearing nude mouse models of human prostate cancer cell line. Seven nude mice were injected with 10mg/kg ICG via tail vein. Near-infrared fluorescence imaging was performed at different time after injection to observe the dynamic characteristics of the transplanted tumor and whole body fluorescence images, and the tumor-to-background ratio (TBR) was calculated. Another three nude mice were injected with 10mg/kg ICG in the same way. After 24h, tumor tissues, different viscera and paraneoplastic adipose tissues were dissected for near-infrared fluorescence imaging. Tumor tissues were taken for pathological section, and the distribution of ICG in tumor tissues was observed under fluorescence microscope. Results The fluorescence intensity at the tumor site of 7 nude mice injected with ICG gradually increased with time, and the background fluorescence around the tumor gradually decreased. After 12h, TBR was the best. The average gray value of each organ of three nude mice was as follows: stomach > large intestine > small intestine > liver > tumor > kidney > peritumoral fat tissue. Under the fluorescence microscope, the tumor tissues showed obvious green fluorescence. Conclusion After intravenous ICG injection, ICG could be concentrated in subcutaneous prostate cancer xenografts through high permeability and retention effect, and the imaging effect is the best in 12-24 hours.

Objective To explore the clinical manifestation, pathological features, treatment regimen and prognosis of primary thyroid lymphoma (PTL) patients. Methods We analyzed retrospectively the clinicopathologic features, diagnosis and treatment of 13 PTL patients confirmed by pathology. Results All patients were B cell non-Hodgkin lymphoma, including three cases of extranodal marginal zone lymphoma and 10 cases of diffuse large B cell lymphoma; 10 patients were in the early stage (stage Ⅰ and Ⅱ) and three patients with advanced stage (stage Ⅲ-Ⅳ); only one patient accepted surgical resection and the rest accepted multi-drug chemotherapy or combined with local radiotherapy; the median survival time was 99.5 months and the 5-year survival rate was 100%. Conclusion The incidence of PTL is low. Thyroid nodules are the main symptoms. More than half of them are accompanied with Hashimoto's thyroiditis. Main pathological type is B cell non-Hodgkin lymphoma. CHOP-based chemotherapy is effective for most of the patients with good prognosis.

Abstract Genetic testing for germline mutations in BRCA1/2 of patients with breast cancer (BC) is part of routine patient care. However, BRCA1/2 mutations account only for a fraction of familial BC. A custom panel of 22 gene sequencing was performed on each patient. Among the 481 female patients, 135 patients were detected to carry pathogenic (P)/likely pathogenic (LP) mutations (28.1%), which corresponded to 12 different cancer predisposition genes [14.6% (70/481) on BRCA1 gene, 5.0% (24/481) on BRCA2 gene, 8.5% (41/481) on non‐BRCA1/2 genes]. Moreover, 24.7% (119/481) of patients had mutation of unknown significance (VUS) in these genes. The most common (8/481) pathogenic mutation is BRCA1 c.5470_5477del, while BRIP1 2392 C > T of patients was detected. All the mutations detected were mainly seen in the homologous recombinant repair pathway. Compared to BRCA2 mutation, BRCA1 mutation is higher in younger female patients (P

Abstract Background This study aimed to determine whether the enhancer of the rudimentary homolog (ERH) gene regulates cell migration and invasion in human bladder urothelial carcinoma (BUC) T24 cells and the underlying mechanism. Methods First, we knocked down ERH in BUC T24 and 5637 cells by shRNA and then used wound healing cell scratch migration assays, transwell cell migration assays, transwell cell invasion chamber experiments and nude mouse tail vein transfer assays to determine the migration and invasion ability after ERH was knocked down. Moreover, we used gene expression profiling chip analysis and further functional experiments to explore the possible mechanism through which ERH knockdown downregulated metastasis ability in T24 cells. Results Wound healing cell scratch migration assays, transwell cell migration assays, transwell cell invasion chamber experiments and nude mouse tail vein transfer assays all showed that the metastasis ability was significantly inhibited in human BUC T24 and 5637 cells with ERH knockdown. A gene expression profiling chip analysis in T24 cells showed that the MYC gene may be an important downstream target of the ERH gene, and the functional experiments showed that MYC is a functional target of ERH in BUC T24 cells. Conclusion ERH knockdown could inhibit the metastasis of BUC T24 cells in vitro and in vivo. This study further explored the mechanism of the ERH gene in the metastasis of the T24 human bladder cancer cell line and found that ERH may regulate MYC gene expression. The results of this research provide a basis for the clinical application of ERH as a potential target for BUC treatment.

Introduction: This study aimed to develop and validate the combination of radiomic features and clinical characteristics that can predict patient survival in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) treated with stereotactic body radiotherapy (SBRT).Materials and Methods: The prediction model was developed in a primary cohort of 70 patients with HCC and PVTT treated with SBRT, using data acquired between December 2015 and June 2017. The radiomic features were extracted from computed tomography (CT) scans. A least absolute shrinkage and selection operator regression model was used to build the model. Multivariate Cox-regression hazard models were created for analyzing survival outcomes and the radiomic features and clinical characteristics were presented with a nomogram. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the model. Participants were divided into a high-risk group and a low-risk group based on the radiomic features.Results: A total of four radiomic features and six clinical characteristics were extracted for survival analysis. A combination of the radiomic features and clinical characteristics resulted in better performance for the estimation of overall survival (OS) [area under the curve (AUC) = 0.859 (CI: 0.770–0.948)] than that with clinical characteristics alone [AUC = 0.761 (CI: 0.641–0.881)]. These patients were divided into high-risk and low-risk groups according to the radiomic features.Conclusion: This study demonstrated that a nomogram of combined radiomic features and clinical characteristics can be conveniently used to assess individualized preoperative prediction of OS in patients with HCC with PVTT before SBRT.

Objective: Accurate staging is of great importance in treatment selection for patients with nasopharyngeal carcinoma (NPC). The aims of this study were to construct radiomic models of NPC staging based on positron emission tomography (PET) and magnetic resonance (MR) images and to investigate the correlation between metabolic parameters and radiomic features.Methods: A total of 100 consecutive cases of NPC (70 in training and 30 in the testing cohort) with undifferentiated carcinoma confirmed pathologically were recruited. Metabolic parameters of the local lesions of NPC were measured. A total of 396 radiomic features based on PET and MRI images were calculated [including histogram, Haralick, shape factor, gray level co-occurrence matrix (GLCM), and run length matrix (RLM)] and selected [using maximum relevance and minimum redundancy (mRMR) and least shrinkage and selection operator (LASSO)], respectively. The logistic regression models were established according to these features. Finally, the relationship between the metabolic parameters and radiomic features was analyzed.Results: We selected the nine most relevant radiomic features (six from MR images and three from PET images) from local NPC lesions. In the PET model, the area under the receiver operating characteristic (ROC) curve (AUC), accuracy, sensitivity, and the specificity of the training group were 0.84, 0.75, 0.90, and 0.69, respectively. In the MR model, those metrics were 0.85, 0.83, 0.75, and 0.86, respectively. Pearson's correlation analysis showed that the metabolic parameters had different degrees of correlation with the selected radiomic features.Conclusion: The PET and MR radiomic models were helpful in the diagnosis of NPC staging. There were correlations between the metabolic parameters and radiomic features of primary NPC based on PET/MR. In the future, PET/MR-based radiomic models, with further improvement and validation, can be a more useful and economical tool for predicting local invasion and distant metastasis of NPC.

Objective: To construct and validate a combined Nomogram model based on radiomic and semantic features to preoperatively classify serous and mucinous pathological types in patients with ovarian cystadenoma.Methods: A total of 103 patients with pathology-confirmed ovarian cystadenoma who underwent CT examination were collected from two institutions. All cases divided into training cohort (N = 73) and external validation cohort (N = 30). The CT semantic features were identified by two abdominal radiologists. The preprocessed initial CT images were used for CT radiomic features extraction. The LASSO regression were applied to identify optimal radiomic features and construct the Radscore. A Nomogram model was constructed combining the Radscore and the optimal semantic feature. The model performance was evaluated by ROC analysis, calibration curve and decision curve analysis (DCA).Result: Five optimal features were ultimately selected and contributed to the Radscore construction. Unilocular/multilocular identification was significant difference from semantic features. The Nomogram model showed a better performance in both training cohort (AUC = 0.94, 95%CI 0.86–0.98) and external validation cohort (AUC = 0.92, 95%CI 0.76–0.98). The calibration curve and DCA analysis indicated a better accuracy of the Nomogram model for classification than either Radscore or the loculus alone.Conclusion: The Nomogram model combined radiomic and semantic features could be used as imaging biomarker for classification of serous and mucinous types of ovarian cystadenomas.

Abstract Background To investigate whether PET/CT-guided bone marrow biopsy adds complementary information for evaluation of bone marrow involvement (BMI) in newly diagnosed lymphomas. Methods Patients with newly diagnosed lymphomas that received both 18F-FDG PET/CT and bone marrow biopsy (BMB) were included in this retrospective study. PET/CT classification of bone lesions was classified as isolated, multifocal (2 lesions or more), diffuse (homogeneous uptake of the entire axial skeleton), or negative. BMBs included PET/CT-guided targeted BMB and/or the routine unilateral iliac crest biopsy. Of 34 patients with focal lesions on PET/CT scan, 30 received both PET/CT-guided targeted BMB and iliac crest biopsy, and 4 patients received targeted biopsy without iliac crest biopsy. The final diagnosis of BMI depends on BMB results. Results A total of 299 patients with lymphomas were included. PET/CT classification of bone lesions was isolated (16/5.4%), multifocal (67/22.4%), diffuse (52/17.4%), and negative (164/54.8%). If only positive iliac crest biopsy was considered as the reference standard, the sensitivity of 18F-FDG PET/CT for identifying focal and diffuse BMI was 48 and 56%, respectively, and the respective specificities were 70 and 83%. Three of 30 patients (10.0%) with focal lesions on PET/CT were confirmed to be false-positive by targeted BMB, and 25 of 30 patients (83.3%) with focal lesions on PET/CT were confirmed as false-negative by iliac crest biopsy. Conclusion It is insufficient to evaluate BMI in newly diagnosed lymphomas using both 18F-FDG PET/CT and routine iliac crest biopsy. 18F-FDG PET/CT imaging should be performed before BMB. In focal bone lesions, PET/CT-guided targeted BMB may complement the results of possible false-positive PET/CT and false-negative iliac crest biopsy findings. However, in diffuse and negative lesions, iliac crest biopsy cannot be safely omitted.

Abstract Background Pancreatic ductal adenocarcinoma has dismal prognosis. Most patients receive radiation therapy (RT), which is complicated by respiration induced organ motion in upper abdomen. The purpose of this study is to report our early clinical experience in a novel self-gated k-space sorted four-dimensional magnetic resonance imaging (4D-MRI) with slab-selective (SS) excitation to highlight tumor infiltrating blood vessels for pancreatic RT. Methods Ten consecutive patients with borderline resectable or locally advanced pancreatic cancer were recruited to the study. Non-contrast 4D-MRI with and without slab-selective excitation and 4D-CT with delay contrast were performed on all patients. Vessel-tissue CNR were calculated for aorta and critical vessels (superior mesenteric artery or superior mesenteric vein) encompassed by tumor. Respiratory motion trajectories for tumor, as well as involved vessels were analyzed on SS-4D-MRI. Intra-class cross correlation (ICC) between tumor volume and involved vessels were calculated. Results Among all 4D imaging modalities evaluated, SS-4D-MRI sampling trajectory results in images with highest vessel-tissue CNR comparing to non-slab-selective 4D-MRI and 4D-CT for all patients studied. Average (±standard deviation) CNR for involved vessels are 13.1 ± 8.4 and 3.2 ± 2.7 for SS-4D-MRI and 4D-CT, respectively. The ICC factors comparing tumor and involved vessels motion trajectories are 0.93 ± 0.10, 0.65 ± 0.31 and 0.77 ± 0.23 for superior-inferior, anterior-posterior and medial-lateral directions respectively. Conclusions A novel 4D-MRI sequence based on 3D-radial sampling and slab-selective excitation has been assessed for pancreatic cancer patients. The non-contrast 4D-MRI images showed significantly better contrast to noise ratio for the vessels that limit tumor resectability compared to 4D-CT with delayed contrast. The sequence has great potential in accurately defining both the tumor and boost volume margins for pancreas RT with simultaneous integrated boost.

Winnie Yeo,1,2 Frankie KF Mo,1,2 Elizabeth Pang,1,2 Joyce JS Suen,1 Jane Koh,1,2 Claudia HW Yip,1 Christopher CH Yip,1 Leung Li,1 Herbert HF Loong,1,2 Giok S Liem1 1Department of Clinical Oncology, Sir YK Pao Centre for Cancer, Prince of Wales Hospital, 2Hong Kong Cancer Institute, State Key Laboratory of Oncology in South China, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong Introduction: Understanding of quality of life (QoL) of young Chinese breast cancer patients after adjuvant cytotoxic chemotherapy is limited. This study aims to assess the QoL of premenopausal Chinese breast cancer women after receiving adjuvant chemotherapy.Patients and methods: Eligibility criteria included stage I–III breast cancer, premenopausal and age ≤45 years at cancer diagnosis and having received adjuvant chemotherapy within 3–10 years before entry to the present study. Patients’ background demographics at the time of breast cancer diagnosis, together with tumor characteristics and anticancer treatments, were collected. At the time of study entry, the menopausal status based on menstrual history, body mass index, and QoL (assessed using Functional Assessment of Cancer Therapy-Breast +4) were recorded.Results: Two hundred and eighty patients were recruited. Ninety-five patients (33.9%) underwent breast-conserving surgery, and nearly all (98.6%) underwent axillary dissection. For adjuvant therapies, 249 patients (88.9%) received anthracycline-containing chemotherapy and 79 (28.2%) received taxane-containing chemotherapy, while 68 (24.3%) received both. One hundred and eighty six patients (66.4%) received adjuvant radiotherapy, and 214 (76.4%) received adjuvant tamoxifen. The median time from breast cancer diagnosis to study entry was 5.01 years. QoL assessment at study entry revealed that older patients had worse social well-being (SWB; mean scores for age ≤40, 41–45, 46–50 and >50 years were 22.0, 19.3, 19.1 and 18.1, respectively, P=0.0442). Patients who underwent axillary dissection had worse scores for breast cancer subscale (BCS; mean score 22.2 vs. 28.3, P=0.0212). Patients who underwent taxane-containing chemotherapy had worse scores for arm subscale (mean score 13.8 vs. 15.3, P=0.0053).Conclusion: At a median follow-up of 5 years post-diagnosis, patients who were younger had fewer disturbances in their SWB. Patients who had axillary dissection had worse BCS scores, while those who received taxane had worse scores for arm subscale. Further studies are warranted for breast-specific QoL to address the specific issues encountered by breast cancer patients. Keywords: cytotoxic, QoL, FACT-B+4, cancer survivors breast, premenopausal

Abstract Background Primary malignant lymphoma of the prostate (PMLP) is prone to occur in the elderly, and it has no significant correlation with lactate dehydrogenase (LDH) and prostate specific antigen (PSA). Clinical symptoms and imaging data of PMLP remain unspecific, and its prognosis is poor. A previous result showed that collapsin response mediator protein 4 (CRMP4) promotor methylation can be used as a predictor for lymph node metastases in prostate biopsies. However, the relationship between CRMP4 promotor methylation and PMLP has not been studied. Methods We investigated the clinicopathological features of PMLP and the significance of CRMP4 methylation in PMLP. The clinical data and diagnosis information of 10 patients with PMLP were retrospectively analyzed. The CRMP4 promotor methylation level in paraffin-embedded tissues of the 10 patients with PMLP were determined and then compared to limited prostate cancer (LPCa) and its negative lymph node tissue [LPCa-LN (−) (10 cases)] and also to metastatic prostate adenocarcinoma (mPCa) and its positive lymph node tissue [mPCa-LN (+) (10 cases)]. Methylation of the CRMP4 promotor in each group was analyzed statistically. A receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of CRMP4 methylation in PMLP. Results The average methylation value of CRMP4 in 10 PMLP patients, 20 cases of prostate adenocarcinoma tissue, 10 cases LPCa-LN (−) and 10 cases mPCa-LN (+) were 42.3, 30.6, 6.7 and 20.3%, respectively. A Kruskal–Wallis test showed that the difference of CRMP4 methylation was significant (X2 = 38.0, P 40.9% could diagnose PMLP. This method had 90% sensitivity and 95% specificity under conditions of CRMP4 methylation > 40.9%. The area under the curve (AUC) was 0.957. Conclusions Methylation of the CRMP4 gene was significantly increased in PMLP, and it is expected to become a new predictor for PMLP.

Background and objective Radiofrequency ablation (RFA) combined with chemotherapy has a certain short-term therapeutic effect for the treatment of advanced non-small cell lung cancer (NSCLC), but whether it can improve the long-term survival rate of patients is still controversy. This study retrospectively analyzed the difference of long-term efficacy between RFA combined with chemotherapy and chemotherapy alone in the treatment of patients with advanced NSCLC. Methods A total of 77 patients with stage IIIb and stage IV NSCLC who underwent radiofrequency ablation and chemotherapy in the Department of Thoracic Surgery, Xuanwu Hospital, Capital University of Medical Sciences from September 2009 to December 2015 were enrolled as the treatment group. Chemotherapy with no radiofrequency ablation was performed in 56 patients with stage IIIb and stage IV NSCLC as the control group. Two groups of patients were followed up by telephone about their living conditions. “Survival” package of R software version 3.4.1 was used for statistical analysis. Two sets of data baseline levels were tested by chi-square test. The bias was processed by Cox regression model and the survival curve was plotted using covariate mean substitution method. Results The first-year survival rate of the treatment group was 70.74%, the two-year survival rate was 39.31% and the median survival time was 22.1 months. The one-year survival rate was 54.54% in the control group, the two-year survival rate was 19.49%, the median survival for 18.1 months. The long-term survival rate of the treatment group was better than that of the control group (P

Purpose: Our purpose was to investigate interfraction setup error of the immobilization device required to implement transperineal ultrasound compared with the current, standard immobilization device. Patient comfort and radiation therapist (RT) satisfaction were also assessed. Methods and materials: Cone beam computed tomography images were acquired before 4069 fractions from 111 patients (control group, n = 56; intervention group, n = 55) were analyzed. The intervention group was immobilized using the Clarity Immobilization System (CIS), comprising a knee rest with autoscan probe kit and transperineal ultrasound probe (n = 55), and control group using a leg immobilizer (LI) (n = 56). Interfraction setup errors were compared for both groups. Weekly questionnaires using a 10-point visual analog scale were administered to both patient groups to measure and compare patient comfort. RT acceptance for both devices was also compared using a survey. Results: There was no significant difference in the magnitude of interfraction cone beam computed tomography–derived setup shifts in the lateral and anteroposterior direction between the LI and CIS (P = .878 and .690, respectively). However, a significant difference (P = .003) was observed in the superoinferior direction between the 2 groups of patients. Patient-reported level of comfort and stability demonstrated no significant difference between groups (P = .994 and .132). RT user acceptance measures for the LI and CIS were ease of handling (100% vs 53.7%), storage (100% vs 61.1%), and cleaning of the devices (100% vs 64.8%), respectively. Conclusions: The CIS demonstrated stability and reproducibility in prostate treatment setup comparable to LI. The CIS device had no impact on patient comfort; however, RTs indicated a preference for LI over the CIS mainly because of its weight and bulkiness.

Background and objective The group of small cell lung cancer (SCLC) are usually highly sensitive to chemotherapy, and less than 15% of them are resistant to drugs. We respectively evaluate the correlation of the sequence and timing of radiotherapy with progression-free survival (PFS) and overall survival (OS) in patients with limited-stage SCLC (LS-SCLC), and to figure out whether concurrent chemoradiotherapy is superior to sequent chemoradiotherapy. Methods Sixty-seven patients diagnosed with LS-SCLC from January 2009 to June 2014 failed to respond to induction chemotherapy. According to the sequence of therapy, they were divided into concurrent chemoradiotherapy group (n=32) and sequent chemoradiotherapy group (n=35). Ninety-four percent of the patients were diagnosed with stage III, and six percent were stage Ib-IIb. Twenty-five patients were treated with prophylactic cranial irradiation (PCI). The Kaplan-Meier method was used to calculate survival time and Log-rank test was used for between-group comparisons. Between-group comparison of categorical data was made by χ2 test. Results In all patients, the 2-year OS, PFS and LC rates were 53.7%, 20.9% and 58.2%. The 2-year OS and PFS rates of concurrent chemoradiotherapy group and sequent chemoradiotherapy were 37.5% vs 54.3% (P=0.048) and 12.5% vs 28.6% (P=0.149). Hematologic toxicities were more common in concurrent group than sequent one (P=0.031), and no statistical difference was observed between the two groups in terms of grade 3 radiation esophagitis, pneumonitis and gastrointestinal reactions (9.4% vs 0, P=0.176; 12.5% vs 2.9%, P=0.318; 12.5% vs 2.9%, P=0.109). Patients treated with PCI have superior OS and PFS comparing with those not (56.0% vs 38.1%, P=0.029; 24% vs 19%, P=0.012). Conclusion Concurrent chemoradiotherapy with original chemotherapy regimens may not be suitable for patients who failed to respond to induction chemotherapy in LS-SCLC, and second-line regimens or radiotherapy alone can be used for them, but prospective trils with large sample are still needed to confirm that.

Objective To investigate the application of dose-volume (DV) combined with equivalent uniform dose (EUD) in the optimization of organ at risk (OAR) in IMRT on nasopharyngeal carcinoma. Methods We selected 55 patients with nasopharyngeal carcinoma who received IMRT planning in the Department of Oncology, The Affiliated Hospital of Southwest Medical University. The optimization methods were divided into conventional DV optimization and DV and EUD combined optimization. The dosages of the target and OAR after two optimization methods were evaluated. Results There was no significant difference in the prescription dose, homogeneity index or conformity index between the two groups (all P > 0.05). We found that the mean OAR doses for DV and EUD combined optimization were significantly lower than those for conventional DV optimization (all P < 0.001). Conclusion DV and EUD combined optimization is successfully applied to the optimization of OAR in IMRT on nasopharyngeal carcinoma, and we give an evaluation methods for the dosimetry of organs at risk in IMRT, in order to reduce the influence of subjective factors.

Background: Myeloid/Lymphoid Neoplasm with FGFR1 Rearrangement is a rare kind of hematological malignant disease.Case presentation: A 37-year-old male patient experienced three distinct disease stages from myeloproliferative neoplasm (MPN), T-cell lymphoblastic lymphoma (T-LBL) to a much more complexed phage of a mixed phenotype acute leukemia (MPAL). Both genetic and genomic alternations were detected including chromosomal abnormality and genic mutations.Result: Karyotyping and fluorescence in situ hybridization (FISH) analysis of either bone marrow or lymph node sample confirmed the presence of the FGFR1 rearrangement. Amplifications of RUNX1, ERG, and U2AF1 genes were identified by next generation sequencing. Furthermore, a frame-shift variant of F330fs*>149 in the RUNX1 gene and a missense mutation of R2263Q in NOTCH1 were also detected.Conclusion: The FGFR1 rearrangement functions as a trigging oncogenic event. Then other genetic events such as RUNX1 and/or NOTCH1 alternations further lead to progression of disease with trilineage blasts assignment.