A despeckling method for ultrasound images utilizing content-aware prior and attention-driven techniques.

The despeckling of ultrasound images contributes to the enhancement of image quality and facilitates precise treatment of conditions such as tumor cancers. However, the use of existing methods for eliminating speckle noise can cause the loss of image texture features, impacting clinical judgment. Thus, maintaining clear lesion boundaries while eliminating speckle noise is a challenging task. This paper presents an innovative approach for denoising ultrasound images using a novel noise reduction network model called content-aware prior and attention-driven (CAPAD). The model employs a neural network to automatically capture the hidden prior features in ultrasound images to guide denoising and embeds the denoiser into the optimization module to simultaneously optimize parameters and noise. Moreover, this model incorporates a content-aware attention module and a loss function that preserves the structural characteristics of the image. These additions enhance the network's capacity to capture and retain valuable information. Extensive qualitative evaluation and quantitative analysis performed on a comprehensive dataset provide compelling evidence of the model's superior denoising capabilities. It excels in noise suppression while successfully preserving the underlying structures within the ultrasound images. Compared to other denoising algorithms, it demonstrates an improvement of approximately 5.88% in PSNR and approximately 3.61% in SSIM. Furthermore, using CAPAD as a preprocessing step for breast tumor segmentation in ultrasound images can greatly improve the accuracy of image segmentation. The experimental results indicate that the utilization of CAPAD leads to a notable enhancement of 10.43% in the AUPRC for breast cancer tumor segmentation.

DUSP1 Signaling Pathway Regulates Cytarabine Sensitivity in Acute Myeloid Leukemia.

Objectives: Dual specificity phosphatase 1 (DUSP1) is high-expressed in various cancers and plays an important role in the cellular response to agents that damage DNA. We aimed to investigate the expressions and mechanisms of DUSP1 signaling pathway regulating cytarabine (Ara-C) resistance in acute myeloid leukemia (AML). Methods: Immunohistochemistry was performed on bone marrow biopsy specimens from AML and controls to explore the expression of DUSP1. Western blot and Q-PCR were used to detect the protein and mRNA expression levels. MTT assay was used to detect the proliferation of cells. Cell apoptosis was detected by flow cytometry. The immune protein-protein interaction (PPI) network of DUSP1 was analyzed in the platform of Pathway Commons, and immune infiltration analysis was used to study the immune microenvironment of AML. Results: We found that the expression levels of DUSP1 in AML patients exceeded that in controls. Survival analysis in public datasets showed that AML patients with higher levels of DUSP1 had poor clinical outcomes. Further public data analysis indicated that DUSP1 was overexpressed in NRAS mutated AML. DUSP1 knockdown by siRNA could sensitize AML cells to Ara-C treatments. The phosphorylation level of mitogen-activated protein kinase (MAPK) pathway was significantly elevated in DUSP1 down-regulated NRAS G13D mutated AML cells. The PPI analysis showed DUSP1 correlated with immune gene CREB1 and CXCL8 in NRAS mutated AML. We also revealed a correlation between tumor-infiltrating immune cells in RAS mutated AML microenvironment. Conclusion: Our findings suggest that DUSP1 signaling pathways may regulate Ara-C sensitivity in AML.

Biomarker Discovery for Early Diagnosis of Papillary Thyroid Carcinoma Using High-Throughput Enhanced Quantitative Plasma Proteomics.

The incidence of thyroid cancer (TC) has been increasing over the last 50 years worldwide. A higher rate of overdiagnosis in indolent thyroid lesions has resulted in unnecessary treatment. An accurate detection of TC at an early stage is highly demanded. We aim to develop an enhanced isobaric labeling-based high-throughput plasma quantitative proteomics to identify biomarkers in a discovery cohort. Selected candidates were tested by enzyme-linked immunosorbent assay (ELISA) in the training cohort and validation cohort. In total, 1063 proteins were quantified, and 129 proteins were differentially expressed between patients and healthy subjects. Serum levels of ISG15 and PLXNB2 were significantly elevated in patients with papillary thyroid cancer (PTC) or thyroid adenoma, compared to healthy subjects (p < 0.001) and patients with nodular goiter (p < 0.001). Receiver operating characteristic (ROC) analysis of combined markers (ISG15 and PLXNB2) significantly distinguished PTC from healthy control (HC) subjects. Similar differentiations were also found between thyroid adenoma and HC subjects. Notably, this combined marker could distinguish stage-I PTC from HC subjects (area under the curve (AUC) = 0.872). Our results revealed that ISG15 and PLXNB2 are independent diagnostic biomarkers for PTC and thyroid adenoma, showing a promising value for the early detection of PTC.

Individualized estimates of intensity-modulated radiotherapy plans after breast conservation surgery for left-sided breast cancer.

OBJECTIVES: The purpose of this study was to explore the influence of individual patient factors, such as volume of the planning target volume (PTV) (VPTV), cardiothoracic ratio (CTR), central lung distance (CLD), and maximal heart distance (MHD), on the design of treatment plans in terms of target dose coverage, integral dose, and dose to organs at risk (OAR) in early breast cancer. METHODS: Ninety-six patients were selected for this study. Radiation doses of 50 Gy and a simultaneous dose of 60 Gy in 25 fractions were administered to the whole breast and tumor bed, respectively. The intensity modulation plan (IMRT) of each patient uses both physical parameters and an equivalent uniform dose (EUD) to optimize the target function. Univariate and multivariate linear regression were used to analyze the relationship between predictive impact factors and OAR percent dose volume, conformity index (CI), and homogeneity index (HI). RESULTS: The average CI and HI values of the left breast cancer plan were 0.595 ± 0.071 (0.3-0.72) and 1.095 ± 0.023 (1.06-1.18), respectively. The CTR (B = 0.21, P = 0.045), VPTV (B = 0.63, P = 0.000), volume of the lung (Vlung) (B = - 0.29, P = 0.005), and MHD (B = 0.22, P = 0.041) were identified as factors influencing the CI index of the left breast cancer intensity modulation plan. VPTV (B = 1.087, P = 0.022) was identified as the influencing factor of the HI index of the left breast cancer intensity modulation plan. volume of the heart (Vheart) (B = - 0.43, P = 0.001) and CLD (B = 0.28, P = 0.008) were influencing factors of the volume of lung (Vlung20) of the lung. The prediction formulas for left-sided breast cancer are noted as follows: CI = 0.459 + 0.19CTR-0.16CLD, Vlung10 = 35.5-0.02Vheart; and Vlung20 = 21.48 + 2.8CLD-0.018Vheart. CONCLUSIONS: CTR, CLD, and MHD can predict the rationality of the parameters of the left breast cancer IMRT. The calculation formula generated based on this information can help the physicist choose the optimal radiation field setting method and improve the quality of the treatment plan.

Combination of Tumor Mutational Burden and DNA Damage Repair Gene Mutations with Stromal/Immune Scores Improved Prognosis Stratification in Patients with Lung Adenocarcinoma.

Background: Both the tumor environment and the genomic landscape of lung cancer may shape patient responses to treatments, including immunotherapy, but their joint impacts on lung adenocarcinoma (LUAD) prognosis are underexplored. Methods: RNA sequencing data and whole-exome sequencing results were downloaded from the TCGA database, and only LUAD-related data were included in this study. Based on gene expression data, the ESTIMATE algorithm was used to estimate stromal and immune scores, and CIBERSORT analysis was used for quantification of the relative abundances of immune cells. Somatic mutations were used for calculating tumor mutation burden (TMB). Specific mutations in genes involved in DNA damage repair (DDR) pathways were identified. The individual and joint associations of stromal and immune score, TMB, and DDR gene mutations with 5-year survival were analyzed by the Kaplan-Meier method and multivariate Cox model. Results: LUAD patients with a high (>highest 25%) stromal or immune score had prolonged survival as compared to those with a low (highest 25%) and low (

Prognostic nomogram and novel risk-scoring system for small cell lung cancer with different patterns of metastases.

OBJECTIVE: This research is aimed to develop the prognostic nomogram and novel risk-scoring system for small cell lung cancer (SCLC) with different patterns of metastases. METHODS: Data on SCLC patients were extracted from the 2010-2015 Surveillance, Epidemiology, and End Results (SEER) database. This nomogram prognostic model was confirmed in the validation cohort. C-index and calibration curve were used to evaluate the accuracy of nomogram model. The predictive capability and net benefit of nomogram was estimated by decision curve analysis (DCA). The cut-off point of the risk stratification system based on nomogram was assessed by X-tile analysis. RESULTS: Our Cox model indicated that age, gender, American Joint Committee on Cancer (AJCC) stage, metastases, chemotherapy, radiation and surgery were independent predictors for OS in SCLC patients. The C-index value of nomogram integrating significant variables for predicting OS in SCLC patients was 0.752 in SEER training set and 0.748 in SEER validation set, respectively. However, the TNM stage only had C-indexes of 0.464 and 0.472 for predicting OS, respectively. The nomogram prognostic model in this study showed higher C-indexes than those in the TNM stage. The C-index value and high quality of calibration plots indicate that the predictive ability of our nomogram model was of great superiority. DCA showed the nomogram had good clinical value. SCLC patients were further divided into low-risk and high-risk group according to nomogram predicted scores. CONCLUSION: Our nomogram model that integrated significant factors can aid as an individualized clinical predictive tool in SCLC patients.

Efficacy and safety of pyrotinib in advanced lung adenocarcinoma with HER2 mutations: a multicenter, single-arm, phase II trial.

BACKGROUND: There is currently a lack of effective treatments for non-small cell lung cancer (NSCLC) patients harboring HER2 mutations. We examined the efficacy and safety of, and potential resistance mechanism to, pyrotinib, a pan-HER inhibitor, in advanced NSCLC carrying HER2 mutations. METHODS: In this multicenter, single-arm, phase II trial, stage IIIB-IV NSCLC patients harboring HER2 mutations, as determined using next-generation sequencing, were enrolled and treated with pyrotinib at a dose of 400 mg/day. The primary endpoint was 6-month progression-free survival (PFS) rate, and secondary endpoints were objective response rate (ORR), PFS, overall survival (OS), disease control rate (DCR), and safety. The impact of different HER2 mutation types on sensitivity to pyrotinib and the potential of utilizing mutational profile derived from circulating tumor DNA (ctDNA) to predict disease progression were also explored. RESULTS: Seventy-eight patients were enrolled for efficacy and safety analysis. The 6-month PFS rate was 49.5% (95% confidence interval [CI], 39.2-60.8). Pyrotinib produced an ORR of 19.2% (95% CI, 11.2-30.0), with median PFS of 5.6 months (95% CI, 2.8-8.4), and median OS of 10.5 months (95% CI, 8.7-12.3). The median duration of response was 9.9 months (95% CI, 6.2-13.6). All treatment-related adverse events (TRAEs) were grade 1-3 (all, 91.0%; grade 3, 20.5%), and the most common TRAE was diarrhea (all, 85.9%; grade 3, 16.7%). Patients with exon 20 and non-exon 20 HER2 mutations had ORRs of 17.7% and 25.0%, respectively. Brain metastases at baseline and prior exposure to afatinib were not associated with ORR, PFS, or OS. Loss of HER2 mutations and appearance of amplification in HER2 and EGFR were detected upon disease progression. CONCLUSIONS: Pyrotinib exhibited promising efficacy and acceptable safety in NSCLC patients carrying exon 20 and non-exon 20 HER2 mutations and is worth further investigation. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR1800020262.

Clinical outcomes of lung adenocarcinoma patients harboring uncommon epidermal growth factor receptor (EGFR) mutations treated with EGFR-tyrosine kinase inhibitors (TKIs).

BACKGROUND: This study aimed to explore the efficacy of different epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma (AC) patients harboring uncommon EGFR mutations. METHODS: Between January 1st, 2013 and October 1st, 2019, 2,680 EGFR mutation-positive patients with confirmed stage IIIB/IV lung AC were enrolled from Zhejiang Cancer Hospital. Uncommon EGFR mutations were detected in 132 patients using next-generation-sequencing. Clinicopathological features between patients with uncommon EGFR mutations and common EGFR mutations were evaluated by the chi-square test. The clinical outcomes of patients with uncommon EGFR mutations were analyzed by the Kaplan-Meier method. RESULTS: Of 132 AC patients with uncommon EGFR mutations, 115 received EGFR-TKIs. Second-generation EGFR-TKIs were associated with longer progression-free survival (PFS) (P=0.116) and overall survival (OS) (P=0.005) than first or third-generation EGFR-TKIs. We also found that patients with compound mutations and double uncommon EGFR mutations had longer PFS (P=0.725) and OS (P=0.741) than those with single uncommon EGFR mutation, although the difference was not significant. In addition, third-generation EGFR-TKIs were more effective than the other two agents in patients with primary T790M mutation regarding PFS (P=0.150) and OS (P=0.033), although the difference in PFS was not significant. CONCLUSIONS: Patients with uncommon EGFR mutations treated with second-generation EGFR-TKIs showed better PFS and OS. EGFR-TKIs were more effective in patients with compound mutations or double uncommon mutations.

Pyrotinib in Patients with HER2-Amplified Advanced Non-Small Cell Lung Cancer: A Prospective, Multicenter, Single-Arm Trial.

PURPOSE: In this study, we aimed to evaluate the efficacy and safety of pyrotinib, a pan-HER inhibitor, in patients with HER2-amplified non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: In this prospective, multicenter, single-arm trial (ChiCTR1800020262), patients with advanced NSCLC with HER2 amplification, as determined by next-generation sequencing, were enrolled and administered pyrotinib orally at 400 mg per day. The primary endpoint was 6-month progression-free survival (PFS) rate. Other endpoints included objective response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), and safety. RESULTS: The enrolled cohort included 27 patients with HER2 amplification. The 6-month PFS rate was 51.9% [95% confidence interval (CI), 34.0-69.3]. The median PFS (mPFS) was 6.3 months (95% CI, 3.0-9.6 months), and median OS was 12.5 months (95% CI, 8.2-16.8 months). Pyrotinib elicited a confirmed ORR of 22.2% (95% CI, 10.6%-40.8%). Patients administered pyrotinib as first-line treatment achieved an mPFS of 12.4 months. Moreover, 30.8% of the patients who had progressed on EGFR tyrosine kinase inhibitor (TKI) responded to pyrotinib. Patients with brain metastases had an ORR of 40%. Treatment-related adverse events (TRAE) occurred in all patients (grade 3, 22.2%), but no grade 4 or higher TRAEs were documented. Diarrhea was the most frequent TRAE (all, 92.6%; grade 3, 7.4%). Loss of HER2 amplification was detected upon disease progression. CONCLUSIONS: Pyrotinib provided antitumor efficacy with a manageable safety profile in HER2-amplified patients with NSCLC.

TROP2 modulates the progression in papillary thyroid carcinoma.

Background: Tumor-associated calcium signal transducer 2 (TROP2) is over expressed in various kinds of human cancers and plays important roles in the proliferation, invasion and metastasis of tumor cells. However, the expression and molecular mechanism of TROP2 in thyroid papillary carcinoma (PTC) are unclear. Methods: The expressions of TROP2 in PTC and control tissue were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. The proliferation and invasion of PTC cell lines were examined by cell cloning and transwell assays. RNA sequencing analysis and public data analysis were assessed to investigate the potential mechanisms of TROP2 in PTC. Gene correlation analysis was conducted to explore the association between TROP2 and the related gene ISG15 in patients with PTC. Results: The expression of TROP2 was significantly higher in PTC than control. The high expression of TROP2 protein was associated with lymph node metastasis, tumor size and capsular infiltration (P<0.05). SiRNA-mediated TROP2 gene expression silencing can significantly inhibit proliferation and migration of PTC cells. ISG15 decreased in TROP2 siRNA PTC cells and increased in PTC patients significantly. There was a significant correlation between the expression of TROP2 and ISG15 in PTC patients. TROP2 interacted directly with ATP6V1A, CEBPA and SOX5 and then further interacted with the immune genes. TROP2 expression and tumor-infiltrating immune cells were also correlated in thyroid cancer microenvironment. Conclusions: TROP2 promotes the development of PTC. TROP2 expression was correlated with ISG15 and tumor-infiltrating immune cells in thyroid cancer.

HER2 transmembrane domain mutation: comprehensive characteristics and real-world evidence of treatment response in Chinese lung adenocarcinoma.

BACKGROUND: HER2 transmembrane domain (TMD) mutation has been reported as a rare driver mutation associated with advanced stage disease and a poor prognosis in patients with lung adenocarcinoma (LUAD). We aimed to comprehensively profile the genetic landscape and treatment response information of HER2 TMD-mutant LUAD. METHODS: An in-house database of 7,812 LUAD patients was screened for mutation prevalence. A multi-center cohort of 16 HER2 V659E-mutant patients and an external cohort of 38 HER2-mutant patients from cBioPortal with overall survival (OS) data were analyzed. Eight patients from the in-house cohort were included in the real-world study of treatment response. Molecular docking simulation and binding affinity prediction were performed. RESULTS: In Chinese LUAD, the prevalence of HER2 TMD mutation was 0.18% (14/7,812), and 0.14% (11/7,812) for the HER2 V659E mutation. The most recurrent co-alteration was TP53 mutation (n=4, 25%) and HER2 amplification (n=2, 12.5%). TMD-mutant patients were diagnosed at more advance stages (P<0.001) and had poorer OS (median OS 10.0 vs. 61.6 months, HR =7.9, 95% CI: 1.0-61.0, P<0.001) than non-TMD mutations. The overall response rate of targeted therapy, chemo-based therapy, and immunotherapy was 57.1%, 22.2%, and 0%, respectively. We postulated to challenge the resistance of tyrosine kinase inhibitor (TKI) with another with stronger binding energy to HER2 and supported the conclusion with a successful case. Additionally, we demonstrated a three-month response to the off-label use of pyrotinib in fifth-line therapy. CONCLUSIONS: Comapred with non-TMD mtuations, HER2 TMD mutation is a rare driver mutation with poorer prognosis in LUAD. Targeted therapy is the dominant choice for patients harboring this targetable mutation and longer OS could possibly be achieved through rechallenge with TKI of stronger binding affinity. Response to fifth-line pyrotinib was observed.

Outcomes of icotinib combined with concurrent chemoradiotherapy in locally advanced cervical cancer.

Concurrent chemoradiotherapy (CRT) based on cisplatin is recognized as the current standard treatment for locally advanced cervical cancer. The treatment of cervical cancer has reached a plateau in the last 20 years. Previous studies have proven that the epidermal growth factor receptor is correlated with chemo- and radioresistance and treatment failure. Hence, the purpose of this study was to investigate the efficacy and safety of icotinib combined with CRT in the treatment of locally advanced cervical cancer. Eligibility criteria included patients treated in the radiotherapy department of Taizhou Central Hospital of Zhejiang Province for stage IIB to IIIB cervical cancers who had not received anti-tumor treatment before and a performance status of 0 to 2. Patients were given icotinib 125 mg three times a day for 6 weeks, which was one week before the start of radiotherapy (500 centigrays in 28 fractions) and chemotherapy (40 mg/m2 administered weekly for 3-5 cycles). There were 29 patients who completed the I+CRT treatment, and it was tolerated well. The median follow-up time was 50 months and 27 patients (93.10%) achieved complete responses. The 5-year cumulative overall survival rate and disease-free survival rate were 58.4% and 60.9%, respectively. The treatment with I+CRT is safe and effective for locally advanced cervical cancer. As far as we know, this is the first study to report the 5-year survival rate of locally advanced cervical cancer with targeted therapy combined with chemoradiotherapy.

Tumor mutation burden in Chinese cancer patients and the underlying driving pathways of high tumor mutation burden across different cancer types.

BACKGROUND: Tumor mutation burden (TMB) has an important association with immunotherapy responses. TMB in the Chinese population has not been well established. Finding differences between the Chinese and Caucasian populations and elucidating the underlying biological mechanisms of high TMB might help develop more precise and effective means for TMB and immunotherapy response prediction. METHODS: Chinese cancer patients fresh tissue (n=2,177), formalin-fixed, paraffin-embed (FFPE) specimens (n=3,294), and pleural fluid (n=189) were profiled using a 295- or 520-gene next-generation sequencing (NGS) panel. The association of the TMB status with a series of molecular features and biological pathways was determined using bootstrapping. RESULTS: TMB, measured by 295- or 520-cancer-related gene panels, was correlated with whole-exome sequencing (WES) TMB based on the in silico simulation in The Cancer Genome Atlas cohort. The median TMB of our data was slightly higher than that from the Foundation Medicine Inc. (FMI) dataset. TMB was also slightly different within the same cancer type between the Chinese and Caucasian population. We discovered that the underlying pathways of TMB status varied greatly and sometimes had an opposite association with TMB across different cancer types. Moreover, we developed a 23-gene and a 16-gene signature to predict TMB prediction for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively, indicating a histology-specific mechanism for driving high-TMB in lung cancer. CONCLUSIONS: TMB varies among different ethnic populations. Our findings extend the knowledge of the underlying biological mechanisms for high TMB and might be helpful for developing more precise and accessible TMB assessment panels and algorithms in more cancer types.

Changes in plasma EBV-DNA and immune status in patients with nasopharyngeal carcinoma after treatment with intensity-modulated radiotherapy.

BACKGROUND: Previous studies reported the early diagnostic values of plasma Epstein-Barr virus (EBV)-DNA. The present study aimed to assess the relationship between the concentration of plasma EBV-DNA and the number of CD8+PD-1+(programmed cell death-1,PD-1) and regulatory T (Treg) cells in patients with nasopharyngeal carcinoma (NPC) who were treated with intensity-modulated radiotherapy (IMRT). METHODS: This study included 37 patients treated with IMRT. Peripheral blood samples were collected two times for each patient, before radiation therapy and 1 week after the treatment. Further, the numbers of CD4+, Treg, CD8+, and CD8+PD1+ cells were determined by flow cytometry. RESULTS: The changes after IMRT were determined by comparing the numbers of neutrophils, lymphocytes, CD4+, Treg, CD8+, CD8+PD1+ cells, and the concentration of plasma EBV-DNA between pretreatment and post-treatment groups. IMRT could reduce the expression level of PD-1 and the number of Treg cells. The concentration of plasma EBV-DNA and the expression level of CD8+PD-1+ were closely associated with the occurrence and development of NPC. Thus, EBV-DNA can be used as an important marker for early diagnosis, and IMRT can strongly reduce the copies of EBV-DNA. CONCLUSIONS: This study showed that IMRT could reverse T-cell exhaustion and reduce the copies of EBV-DNA. In clinical practice, plasma EBV-DNA is a sensitive biomarker for diagnosis, prognosis, and evaluation of clinical efficacy.

Unique genomic profiles obtained from cerebrospinal fluid cell-free DNA of non-small cell lung cancer patients with leptomeningeal metastases.

BACKGROUND: Leptomeningeal metastases (LM), associated with poor prognosis, are frequent complications of advanced non-small cell lung cancer (NSCLC) patients, especially in patients with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the mutational landscape of LM has not been comprehensively investigated in large cohorts and the underlining biology of LM remains elusive. Some studies have explored the potential of cerebrospinal fluid (CSF) in reflecting the molecular profile of LM but with limited number of patients enrolled. METHODS: In this study, we performed capture-based targeted sequencing using a panel consisting of 168 lung cancer-related genes on matched CSF and plasma samples from 72 advanced NSCLC patients with confirmed LM to interrogate the potential of CSF as a source of liquid biopsy. RESULTS: We revealed a rate of detection of 81.5% and 62.5% for CSF and plasma, respectively (p = 0.008). The maximum allelic fraction (MaxAF) was also significantly higher in CSF (43.6% vs. 4.6%) (p < 0.001). CSF, harboring a unique genomic profile by having a significant number of CSF-specific mutations, primarily copy number variations, is superior to plasma in reflecting the mutational profile of LM. Further pathway enrichment analysis revealed that most of CSF-specific mutations participated in pathways relevant to the tumorigenesis and the development of metastases. Moreover, our data also revealed that TP53 loss of heterozygosity (LOH) predominantly existed in CSF (p < 0.001). CONCLUSIONS: Collectively, we demonstrated that CSF provides a more comprehensive profile of LM than plasma in a large cohort, thus can be used as an alternative source of liquid biopsy for LM patients.

High HLA-F Expression Is a Poor Prognosis Factor in Patients with Nasopharyngeal Carcinoma.

BACKGROUND AND AIMS: In patients with nasopharyngeal carcinoma (NPC), local treatment failure and distant metastasis contribute largely to poor outcomes. The nasopharynx is an important lymphoid tissue, and NPC tumourigenesis and development are partly attributed to immune system disorders. Human leukocyte antigen F (HLA-F) has shown a close correlation with NPC in many genome-wide association studies (GWASs). However, clinical studies rarely explore the relationship of HLA-F expression with the clinical parameters and outcomes in patients with NPC. METHODS: In this study, we used immunohistochemistry to evaluate HLA-F expression in 74 paraffin-embedded NPC tissue sections and then analysed the association between HLA-F expression and clinical parameters and outcomes. The plasma concentration of soluble HLA-F (sHLA-F) in NPC patients and normal controls was also detected, via enzyme-linked immunosorbent assay (ELISA). RESULTS: Low, moderate, and high HLA-F expression levels were observed in 47.3% (35/74), 35.1% (26/74), and 17.6% (13/74), respectively, of the tissue samples. HLA-F expression showed a significant correlation with local recurrence (p = 0.037) and distant metastasis (p = 0.024) and was also an independent factor for local recurrence-free survival (LRFS; p = 0.016) and distant metastasis-free survival (DMFS; p = 0.004). Although the mean concentration of plasma sHLA-F in the NPC patients was higher than that in the normal controls (13.63 pg/ml vs. 10.06 pg/ml), no statistical significance was observed (p = 0.118). CONCLUSIONS: Our study provides the first evidence that high HLA-F expression is associated with NPC local recurrence and distant metastasis and may be regarded as a poor prognostic factor for NPC patients. Additional studies using larger sample sizes may be necessary to determine whether sHLA-F is a feasible NPC diagnostic indicator.

Outcome and prognostic factors in cervical cancer patients treated with surgery and concurrent chemoradiotherapy: a retrospective study.

BACKGROUND: The objective of this study is to analyze the treatment outcome and secondary reactions in 98 patients with stage I-III cervical carcinoma who underwent postoperative radiotherapy. METHODS: From 2006 to 2014, 98 patients with stage I-III cervical carcinoma were treated with postoperative radiotherapy. The major histological type, found in 92.86% of the patients (91 cases), was squamous cell carcinoma. Patients were staged according to the 2002 TNM guidelines. The postoperative radiotherapy methods included two-field irradiation (16 patients, 16.32%), four-field box irradiation (16 patients, 16.32%), and intensity-modulated radiotherapy (IMRT; 66 patients, 67.36%). The survival rates were represented using Kaplan-Meier curves, and prognosis analyses were performed using Cox multivariate analyses. RESULTS: The 5-year overall survival and progression-free survival rates were 82.0 and 76.0%, respectively. Only one patient (1.02%) developed a grade 3 acute radiation enteritis, while grade 3 and 4 myelosuppression was noted in 17 patients (17.35%) and one patient (1.02%), respectively. Multivariate analyses showed that anemia before radiotherapy and tumor size were predictors of the OS (P = 0.008, P = 0.045) rates. CONCLUSIONS: Postoperative radiotherapy for patients with risk factors of cervical cancer procured good efficacy levels with mild side effects. Anemia and tumor size were important OS predictors.

Expression of HIF-1α and HIF-2α correlates to biological and clinical significance in papillary thyroid carcinoma.

BACKGROUND: The aim of this study was to detect the expression of hypoxia-inducible factor (HIF)-1α and HIF-2α in papillary thyroid carcinoma (PTC) compared with normal thyroid tissues. METHODS: The mRNA levels and protein levels of HIF-1α and HIF-2α were detected by real-time PCR and Western blot separately in 30 pairs of PTCs and normal thyroid cases. The protein levels were also detected by immunohistochemistry (IHC) using 92 samples of PTC group and 46 normal samples as control group for analyzing the biological and clinical significance of the expression of HIF-1α/HIF-2α. RESULTS: Real-time PCR results showed the mRNA level of HIF-1α and HIF-2α were significantly higher in PTC than normal group (P<0.001). Also, significantly higher positive rates (73%/65%) of HIF-1α and HIF-2α were observed in PTC compared with the control group (27%/35%) by IHC (P<0.01); the consistent results were gotten with Western blot. Although we did not find a significant correlation between the expression of HIF-1α and HIF-2α with gender, age, calcification, or Hashimoto's disease in the present study (P>0.05), both of their expressions were correlated to lymph node metastasis (P<0.05), capsular invasion (P<0.05), and TNM stage (P<0.05). CONCLUSIONS: Overexpression of HIF-1α and HIF-2α are associated with the carcinogenesis of PTC, served as potential biomarkers of PTC.

A planning study of simultaneous integrated boost with forward IMRT for multiple brain metastases.

The objective of this study was to evaluate the dose conformity and feasibility of whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in patients with 1 to 3 brain metastases. Forward intensity-modulated radiation therapy plans were generated for 10 patients with 1 to 3 brain metastases on Pinnacle 6.2 Treatment Planning System. The prescribed dose was 30 Gy to the whole brain (planning target volume [PTV]wbrt) and 40 Gy to individual brain metastases (PTVboost) simultaneously, and both doses were given in 10 fractions. The maximum diameters of individual brain metastases ranged from 1.6 to 6 cm, and the summated PTVs per patient ranged from 1.62 to 69.81 cm(3). Conformity and feasibility were evaluated regarding conformation number and treatment delivery time. One hundred percent volume of the PTVboost received at least 95% of the prescribed dose in all cases. The maximum doses were less than 110% of the prescribed dose to the PTVboost, and all of the hot spots were within the PTVboost. The volume of the PTVwbrt that received at least 95% of the prescribed dose ranged from 99.2% to 100%. The mean values of conformation number were 0.682. The mean treatment delivery time was 2.79 minutes. Ten beams were used on an average in these plans. Whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in 1 to 3 brain metastases is feasible, and treatment delivery time is short.