The impact of submandibular glands protection on xerostomia as monitored by diffusion-weighted imaging in nasopharyngeal carcinoma patients.

PURPOSE: To determine the impact of sparing submandibular glands (SMGs) on alleviating xerostomia and the functional dynamics of the irradiated parotid glands (PGs) and sublingual glands (SLGs) by diffusion-weighted imaging. METHODS: 97 participants underwent 9 rounds of DWI scans before IC (pre-IC), pre-radiation (pre-RT), the midpoint of radiation (mid-RT), the end of radiation (post-RT), 1, 3, 6, 9, 12 (12m-RT) months following radiation. Apparent diffusion coefficient of SMGs (ADCSMG), PGs (ADCPG), and SLGs (ADCSLG), xerostomia questionnaire scores (XQ), and saliva flow rate measures under unstimulated (uSFR) and stimulated condition (sSFR) were documented. RESULTS: ADCPG, ADCSMG, ADCSLG, and XQ showed a rapid increase with a top at 3m-RT followed by regression, whereas uSFR and sSFR had the reverse trend. The change rate of ADC correlated with the dose to PGs, SMGs, and SLGs, as well as uSFR, sSFR, and XQ scores (p < 0.05 for all, except for uSFR with ADCPG (p = 0.063)). Maingroup for ADCPG, uSFR, and sSFR were significant (p values were 0.028, 0.000, 0.000 respectively); ADCPG in SMG sparing group was lower while uSFR, and sSFR were higher than those in the SMG-unsparing group. Simplegroup for ADCSMG, ADCSLG (all p < 0.05 from mid-RT to 12m-RT), and XQ (all p < 0.001 at mid-, 6m-, 9m-, and 12m-RT) were significant; ADCSMG, ADCSLG, and XQ were lower in the SMG-sparing group. CONCLUSIONS: SMG protection has a great impact on the functional retention of PGs and SLGs, resulting in alleviating xerostomia and improving quality of life. TRIAL REGISTRATION: The clinical trial was also registered with the Chinese Clinical Study Registry (registered number: ChiCTR1900024328, Date: July 6, 2019; URL: https://www.chictr.org.cn/showproj.aspx?proj=40726 ).

Applying a novel two-step deep learning network to improve the automatic delineation of esophagus in non-small cell lung cancer radiotherapy.

Purpose: To introduce a model for automatic segmentation of thoracic organs at risk (OARs), especially the esophagus, in non-small cell lung cancer radiotherapy, using a novel two-step deep learning network. Materials and methods: A total of 59 lung cancer patients' CT images were enrolled, of which 39 patients were randomly selected as the training set, 8 patients as the validation set, and 12 patients as the testing set. The automatic segmentations of the six OARs including the esophagus were carried out. In addition, two sets of treatment plans were made on the basis of the manually delineated tumor and OARs (Plan1) as well as the manually delineated tumor and the automatically delineated OARs (Plan2). The Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and average surface distance (ASD) of the proposed model were compared with those of U-Net as a benchmark. Next, two groups of plans were also compared according to the dose-volume histogram parameters. Results: The DSC, HD95, and ASD of the proposed model were better than those of U-Net, while the two groups of plans were almost the same. The highest mean DSC of the proposed method was 0.94 for the left lung, and the lowest HD95 and ASD were 3.78 and 1.16 mm for the trachea, respectively. Moreover, the DSC reached 0.73 for the esophagus. Conclusions: The two-step segmentation method can accurately segment the OARs of lung cancer. The mean DSC of the esophagus realized preliminary clinical significance (>0.70). Choosing different deep learning networks based on different characteristics of organs offers a new option for automatic segmentation in radiotherapy.

Development and validation of a nomogram for prediction of recovery from moderate-severe xerostomia post-radiotherapy in nasopharyngeal carcinoma patients.

PURPOSE: Aim to create and validate a comprehensive nomogram capable of accurately predicting the transition from moderate-severe to normal-mild xerostomia post-radiotherapy (postRT) in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We constructed and internally verified a prediction model using a primary cohort comprising 223 patients who were pathologically diagnosed with NPC from February 2016 to December 2019. LASSO regression model was used to identify the clinical factors and relevant variables (the pre-radiotherapy (XQ-preRT) and immediate post-radiotherapy (XQ-postRT) xerostomia questionnaire scores, as well as the mean dose (Dmean) delivered to the parotid gland (PG), submandibular gland (SMG), sublingual gland (SLG), tubarial gland (TG), and oral cavity). Cox proportional hazards regression analysis was performed to develop the prediction model, which was presented as a nomogram. The models' performance with regard to calibration, discrimination, and clinical usefulness was evaluated. The external validation cohort comprised 78 patients. RESULTS: Due to better discrimination and calibration in the training cohort, age, gender, XQ-postRT, and Dmean of PG, SMG, and TG were included in the individualized prediction model (C-index of 0.741 (95% CI:0.717 to 0.765). Verification of the nomogram's performance in internal and external validation cohorts revealed good discrimination (C-index of 0.729 (0.692 to 0.766) and 0.736 (0.702 to 0.770), respectively) and calibration. Decision curve analysis revealed that the nomogram was clinically useful. The 12-month and 24-month moderate-severe xerostomia rate was statistically lower in the SMG-spared arm (28.4% (0.230 to 35.2) and 5.2% (0.029 to 0.093), respectively) than that in SMG-unspared arm (56.8% (0.474 to 0.672) and 12.5% (0.070 to 0.223), respectively), with an HR of 1.84 (95%CI: 1.412 to 2.397, p = 0.000). The difference in restricted mean survival time for remaining moderate-severe xerostomia between the two arms at 24 months was 5.757 months (95% CI, 3.863 to 7.651; p = 0.000). CONCLUSION: The developed nomogram, incorporating age, gender, XQ-postRT, and Dmean to PG, SMG, and TG, can be used for predicting recovery from moderate-severe xerostomia post-radiotherapy in NPC patients. Sparing SMG is highly important for the patient's recovery.

Automatic segmentation of the tumor in nonsmall-cell lung cancer by combining coarse and fine segmentation.

OBJECTIVES: Radiotherapy plays an important role in the treatment of nonsmall-cell lung cancer (NSCLC). Accurate delineation of tumor is the key to successful radiotherapy. Compared with the commonly used manual delineation ways, which are time-consuming and laborious, the automatic segmentation methods based on deep learning can greatly improve the treatment efficiency. METHODS: In this paper, we introduce an automatic segmentation method by combining coarse and fine segmentations for NSCLC. Coarse segmentation network is the first level, identifing the rough region of the tumor. In this network, according to the tissue structure distribution of the thoracic cavity where tumor is located, we designed a competition method between tumors and organs at risk (OARs), which can increase the proportion of the identified tumor covering the ground truth and reduce false identification. Fine segmentation network is the second level, carrying out precise segmentation on the results of the coarse level. These two networks are independent of each other during training. When they are used, morphological processing of small scale corrosion and large scale expansion is used for the coarse segmentation results, and the outcomes are sent to the fine segmentation part as input, so as to achieve the complementary advantages of the two networks. RESULTS: In the experiment, CT images of 200 patients with NSCLC are used to train the network, and CT images of 60 patients are used to test. Finally, our method produced the Dice similarity coefficient of 0.78 ± 0.10. CONCLUSIONS: The experimental results show that the proposed method can accurately segment the tumor with NSCLC, and can also provide support for clinical diagnosis and treatment.

Application of Diffusion Kurtosis Imaging in Evaluating Acute Xerostomia in Nasopharyngeal Carcinoma Treated With Induction Chemotherapy Plus Concurrent Chemoradiotherapy.

Purpose: The aim of this study was to identify the efficacy of diffusion kurtosis imaging (DKI) in tracking and monitoring the dynamic change of parotid glands (PGs), submandibular glands (SMGs), sublingual glands (SLGs), and acute xerostomia in nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT). Methods: The prospective study recruited 42 participants treated with IC+CCRT. All patients underwent DKI scanning six times: before IC, before RT, in the middle of the RT course, immediately after RT, and 1 and 3 months post-RT. Mean diffusion coefficient (MD) and mean kurtosis (MK) of PG, SMG, SLG, saliva flow rate measured under resting (uSFR) and stimulated condition (sSFR), and xerostomia questionnaire (XQ) scores were recorded. Results: At each time point, sSFR was significantly higher than uSFR (p < 0.05 for all). MD of the salivary glands and XQ scores increased over time while MK, uSFR, and sSFR decreased. After IC, the significant differences were detected in MD and MK of bilateral SMG and MK of the left SLG (p < 0.05 for all), but not in MD and MK of PG, uSFR, sSFR, and XQ scores. After RT, sSFR at 1m-RT decreased significantly (p = 0.03) while no significant differences were detected in uSFR and XQ scores. Moderate-strong correlations were detected in ΔMD-PG-R%, ΔMK-PG-R%, ΔMD-PG-L%, ΔMK-PG-L%, ΔMD-SMG-R%, ΔMK-SMG-R%, ΔMD-SMG-L%, ΔMK-SMG-L%, and ΔMD-SLG-R%, with correlation coefficients (p < 0.05 for all) ranging from 0.401 to 0.714. ΔuSFR% was correlated with ΔMD-SMG% (p = 0.01, r = -0.39), ΔMD-SLG% (p < 0.001, r = -0.532), and ΔMK-SMG% (p < 0.001, r = -0.493). ΔsSFR% correlated with ΔMD-PG% (p = 0.001, r = -0.509), ΔMD-SMG% (p = 0.015, r = -0.221), and ΔMK-PG% (p < 0.001, r = 0.524). ΔXQ% was only correlated with ΔMK-PG% (p = 0.004, r = 0.433). Conclusion: DKI is a promising tool for tracking and monitoring the acute damage of PG, SMG, and SLG induced by IC+CCRT in NPC patients.

Geometric and Dosimetric Evaluation of the Automatic Delineation of Organs at Risk (OARs) in Non-Small-Cell Lung Cancer Radiotherapy Based on a Modified DenseNet Deep Learning Network.

Purpose: To introduce an end-to-end automatic segmentation model for organs at risk (OARs) in thoracic CT images based on modified DenseNet, and reduce the workload of radiation oncologists. Materials and Methods: The computed tomography (CT) images of 36 lung cancer patients were included in this study, of which 27 patients' images were randomly selected as the training set, 9 patients' as the testing set. The validation set was generated by cross validation and 6 patients' images were randomly selected from the training set during each epoch as the validation set. The autosegmentation task of the left and right lungs, spinal cord, heart, trachea and esophagus was implemented, and the whole training time was approximately 5 hours. Geometric evaluation metrics including the Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95) and average surface distance (ASD), were used to assess the autosegmentation performance of OARs based on the proposed model and were compared with those based on U-Net as benchmarks. Then, two sets of treatment plans were optimized based on the manually contoured targets and OARs (Plan1), as well as the manually contours targets and the automatically contoured OARs (Plan2). Dosimetric parameters, including Dmax, Dmean and Vx, of OARs were obtained and compared. Results: The DSC, HD95 and ASD of the proposed model were better than those of U-Net. The differences in the DSC of the spinal cord and esophagus, differences in the HD95 of the spinal cord, heart, trachea and esophagus, as well as differences in the ASD of the spinal cord were statistically significant between the two models (P<0.05). The differences in the dose-volume parameters of the two sets of plans were not statistically significant (P>0.05). Moreover, compared with manual segmentation, autosegmentation significantly reduced the contouring time by nearly 40.7% (P<0.05). Conclusions: The bilateral lungs, spinal cord, heart and trachea could be accurately delineated using the proposed model in this study; however, the automatic segmentation effect of the esophagus must still be further improved. The concept of feature map reuse provides a new idea for automatic medical image segmentation.

Hypofractionated radiotherapy in ten fractions for postmastectomy patients: a phase II study compared with another hypofractionation schedule with sixteen fractions.

BACKGROUND: The purpose of this phase II study was to evaluate the feasibility of hypofractionated radiotherapy (HFRT) with a dose of 36.5 Gy in 10 fractions in postmastectomy patients. METHODS: From March 2014 to December 2015, 85 patients with locally advanced breast cancer were eligible to participate in this study with a schedule of 36.5 Gy in 10 fractions. Intensity-modulated radiation therapy (IMRT) was delivered to the chest wall with or without the supraclavicular region. The primary endpoint was radiation-related toxicities. The secondary endpoints were locoregional failure-free survival (LRFFS), disease-free survival (DFS) and overall survival (OS). And the outcomes were compared with our retrospective study of 72 patients with 42.5 Gy in 16 fractions. RESULTS: The median follow-up was 69.0 (range 66.5-71.5) months in the 36.5 Gy group and 93.0 (range 91.9-94.1) months in the 42.5 Gy group, respectively. Radiation-related toxicities were mainly grade 1, although a few patients had grade 2 plexopathy (1.2%) and acute skin toxicity (1.2%) in the 36.5 Gy group, and grade 2 acute skin toxicity (5.6%) and lymphedema (4.2%) in the 42.5 Gy group. There were no significant differences between the groups in acute and late toxicities. For all the patients, the 5-year LRFFS, DFS and OS were 97.7 and 100.0%, 93.1 and 90.3%, 98.8 and 97.2%, respectively, without significant differences between the groups. CONCLUSION: Postmastectomy HFRT with a schedule of 36.5 Gy in 10 fractions was feasible, with mild toxicities and excellent 5-year clinical outcome. TRIAL REGISTRATION: Trial registration number: ChiCTR-ONRC-14004391 . Date of registration: 9/3/2014.

Effects of salbutamol on the kinetics of sevoflurane and the occurrence of early postoperative pulmonary complications in patients with mild-to-moderate chronic obstructive pulmonary disease: A randomized controlled study.

Bronchodilators dilate the bronchi and increase lung volumes, thereby improving respiratory physiology in patients with chronic obstructive pulmonary disease (COPD). However, their effects on sevoflurane kinetics remain unknown. We aimed to determine whether inhaled salbutamol affected the wash-in and wash-out kinetics of sevoflurane and the occurrence of early postoperative pulmonary complications (PPCs) in patients with COPD undergoing elective surgery. This randomized, placebo-controlled study included 63 consecutive patients with COPD allocated to the salbutamol (n = 30) and control groups (n = 33). The salbutamol group received salbutamol aerosol (2 puffs of ~200 µg) 30 min before anesthesia induction and 30 min before surgery completion. The control group received a placebo. Sevoflurane kinetics were determined by collecting end-tidal samples from the first breaths at 1, 2, 3, 4, 5, 7, 10, and 15 min before the surgery (wash-in) and after closing the vaporizer (wash-out). PPCs were recorded for 7 days. The salbutamol group had higher end-tidal to inhaled sevoflurane ratios (p<0.05, p<0.01) than the control group, from 3 to 10 min during the wash-in period, but no significant differences were observed during the wash-out period. The arterial partial pressure of oxygen to the fraction of inhaled oxygen was significantly higher in the salbutamol group at 30 (320.3±17.6 vs. 291.5±29.6 mmHg; p = 0.033) and 60 min (327.8±32.3 vs. 309.2±30.5 mmHg; p = 0.003). The dead space to tidal volume ratios at 30 (20.5±6.4% vs. 26.3±6.0%, p = 0.042) and 60 min (19.6±5.1% vs. 24.8±5.5%, p = 0.007) and the incidence of bronchospasm (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.23-0.67, p = 0.023) and respiratory infiltration (OR 0.52, 95% CI, 0.40-0.65, p = 0.017) were lower in the salbutamol group. In patients with COPD, salbutamol accelerates the wash-in rate of sevoflurane and decreases the occurrence of postoperative bronchospasm and pulmonary infiltration within the first 7 days.

Dosimetric evaluation of helical tomotherapy and volumetric-modulated arc therapy for malignant pleural mesothelioma: a planning study for dose escalation.

BACKGROUND: To compare the dosimetric differences between helical tomotherapy (HT) and volumetric-modulated arc therapy (VMAT) treatment plans for inoperable malignant pleural mesothelioma (MPM). METHODS: Ten patients with inoperable MPM were retrospectively planned with the HT and VMAT techniques, and the dose-volume histogram (DVH)-based parameters of the planning target volume (PTV) and organs at risk (OARs) were compared. RESULTS: Compared with the VMAT plans, the target homogeneity index (HI) and conformity index (CI) of the HT plans were significantly better (HI: 1.04±0.01 vs. 1.11±0.03, CI: 0.80±0.07 vs. 0.71±0.12, respectively) (P<0.001, P=0.013, respectively). Regarding the OARs, including the ipsilateral lung, contralateral lung, heart, and spinal cord, the differences among the V30 (Vx: fraction of volume receiving >5, 10, 20, and 30 Gy, respectively) of the ipsilateral lung and V5, V10, and V20 of the contralateral lung were statistically significant (P=0.031, P=0.030, P=0.021, P=0.003, respectively). However, there was no significant differences between HT plans and VMAT plans, regarding the V5, V10 and V20 of the ipsilateral lung, V3 of the contralateral lung, V5 and Dmean of the heart, and Dmax of the cord. The treatment delivery time of the VMAT was significantly shorter than that of the HT (mean delivery time: 3.27±1.65 vs. 11.11±3.75 min, respectively) (P<0.001). CONCLUSIONS: Compared to the VMAT plans, the HT plans not only demonstrated more optimal target coverage and conformity but also considerably reduced the dose-volume parameters of the OARs in both low-dose areas in contralateral lung and high-dose areas in ipsilateral lung and contralateral lung, which is correlated to radiation injury. However, the treatment delivery time of the HT plans was longer.

Preliminary results on anal cancer by applying intensity modulated radiotherapy and synchronous capecitabine chemotherapy simultaneously.

BACKGROUND: Anal cancer is a rare clinical disease with the incidence rate of 1-2/10 million. The present study aims to assess the feasibility, safety and short-term outcome of the simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) schedule with oral capecitabine in patients with anal cancer. METHODS: From September 2009 to February 2014, a total of 10 patients with anal carcinoma were treated with SIB-IMRT in 32 daily fractions of 1.8 Gy to the primary tumor and macroscopically involved lymph nodes and 32 fractions of 1.55 Gy electively to the bilateral iliac and inguinal lymph node areas with concurrent capecitabine 625 mg/m2 twice daily 5 days/week. Two patients received a sequential radiation boost dose of 2×1.8 Gy on macroscopic residual tumor in week 5 of treatment. Acute and late toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. RESULTS: All patients completed chemoradiation without any treatment break. Grade 3 acute skin toxicity was observed in 4 patients (40%). No grade 4 toxicity was observed. Mean follow-up was 20 months (range: 6-60 months). The 2-year-local control, colostomy-free survival, distant metastases-free survival and overall survival (OS) rates were 100% (10/10), 90% (9/10), 90% (9/10), and 90% (9/10), respectively. CONCLUSIONS: SIB-IMRT with concomitant capecitabine 625 mg/m2 b.i.d. on irradiation days resulted in an acceptable safety profile, and proved to be a tolerable and effective treatment regimen for locally advanced anal cancer. However, a larger number of patients and a longer follow-up are required to assess its potential superiority.

Expression of ICOSL is associated with decreased survival in invasive breast cancer.

BACKGROUND: Inducible co-stimulator (ICOS) is a CD28-related molecule exclusively expressed on activated T cells and plays a critical role in modulating the immune response in breast cancer. The blockage of ICOS pathway has been shown to inhibit the activity of Type 2 T helper cells, thus potentially protecting against cancer growth. The current study aims to investigate the correlation between inducible co-stimulator ligand (ICOSL) expression in tumor tissues and the prognoses of patients with invasive breast cancer. METHODS: Tumor samples from 562 Chinese patients with invasive breast carcinomas were collected between 2003 and 2010. The expression of ICOSL on breast tumor and adjacent non-cancerous tissue was determined via immunohistochemistry. The overall survival (OS) of patients with positive and negative ICOSL expression were described using Kaplan-Meier curves, respectively. Parametric correlation method was used to analyze the correlation between ICOSL expression and other clinicopathological parameters. ICOSL was selected as a dependent variable for multivariate analysis. RESULTS: Positive ICOSL expression was identified on the plasma membrane in both cytoplasm and the nucleus of breast cancer cells. Membrane-expressed ICOSL is determined as an independent prognostic factor for OS in breast cancer but without significantly correlating with other clinicopathologic parameters such as age, menopausal status, depth of invasion, lymph node metastasis status, histologic classification, etc. CONCLUSION: Our study suggests that the up-regulated expression of ICOSL protein in breast tumor cells can be associated with poor prognoses in invasive breast carcinomas.

Predictive value of excision repair cross-complementing group 2 gene Lys751Gln and Asp312Asn polymorphisms in melanoma risk.

Epidemiological studies have assessed the association between excision repair cross-complementing group 2 (ERCC2) Lys751Gln and Asp312Asn polymorphisms and melanoma risk with conflicting results. Relevant articles were searched from PubMed, Embase, and Web of Science with a time limit of 3 September 2016. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. We performed this meta-analysis with 12 studies including 6157 cases and 8873 controls for Lys751Gln and nine studies including 5037 cases and 7542 controls for Asp312Asn polymorphism. Overall, no significant associations were found under all the models for Lys751Gln polymorphism, and significant associations were found for Asp312Asn polymorphism for AA versus GG (OR=1.12, 95% CI=1.00-1.26) and for the recessive model (OR=1.11, 95% CI=1.00-1.24). In the stratification analyses by source of control: for Lys751Gln polymorphism, significant associations were found for CC versus AA (OR=1.19, 95% CI=1.04-1.36) and the recessive model (OR=1.15, 95% CI=1.02-1.30); for Asp312Asn polymorphism, significant associations were found for AA versus GG (OR=1.31, 95% CI=1.11-1.53) and the recessive model (OR=1.29, 95% CI=1.11-1.50). This meta-analysis suggested that both the Lys751Gln and Asp312Asn polymorphisms were risk factors for melanoma risk in population-based subgroup.

MicroRNA-330 inhibited cell proliferation and enhanced chemosensitivity to 5-fluorouracil in colorectal cancer by directly targeting thymidylate synthase.

Colorectal cancer (CRC) is the third most common cancer in males and the second most common in females, worldwide. Currently, 5-fluorouracil (5-FU)-mediated chemotherapy is the adjuvant treatment for patients with CRC following surgical resection. However, a number of patients with CRC develop 5-FU resistance, which is a major challenge for the effective treatment of cancer. Therefore, it is important to investigate the molecular mechanisms underlying chemoresistance and the therapeutic treatments that may improve the treatment of CRC. The present study demonstrated that microRNA (miR)-330 was significantly downregulated in CRC tissues and cell lines. Ectopic miR-330 expression decreased cell proliferation and enhanced cell chemosensitivity to 5-FU via the cell apoptosis pathway in CRC. In addition, thymidylate synthase (TYMS) was revealed to be a direct target gene of miR-330 in CRC. Knockdown of TYMS inhibited CRC cell proliferation, and enhanced cell chemosensitivity to 5-FU by promoting cell apoptosis. In conclusion, the results of the present study indicated that miR-330 targeted TYMS to inhibit the proliferation and enhance the chemosensitivity of CRC cells to 5-FU by promoting cell apoptosis. The present study provided important insight into the molecular mechanism underlying 5-FU-mediated chemoresistance and a novel therapeutic strategy for the enhancement of efficacy in CRC treatment.

The Expression and Clinical Outcome of pCHK2-Thr68 and pCDC25C-Ser216 in Breast Cancer.

Checkpoint kinase 2 (CHK2) and cell division cycle 25C (CDC25C) are two proteins involved in the DNA damage response pathway, playing essential roles in maintaining genome integrity. As one of the major hallmarks of abnormal cellular division, genomic instability occurs in most cancers. In this study, we identified the functional expression of pCHK2-Thr68 and pCDC25C-Ser216 in breast cancer, as well as its association with breast cancer survival. Tissue microarray analysis using immunohistochemistry was constructed to identify the expression of pCHK2-Thr68 and pCDC25C-Ser216 in 292 female breast cancer patients. The relationship among protein expression, clinicopathological factors (e.g., human epidermal growth factor receptor 2 (HER 2), tumor size, tumor-node-metastasis (TNM) classification), and overall survival of the breast cancer tissues were analyzed using Pearson's χ-square (χ²) test, Fisher's exact test, multivariate logistic regression and Kaplan-Meier survival analysis. Significantly higher expressions of pCHK2-Thr68 and pCDC25C-Ser216 were observed in the nucleus of the breast cancer cells compared to the paracancerous tissue (pCHK2-Thr68, 20.38% vs. 0%; pCDC25C-Ser216, 82.26% vs. 24.24%). The expression of pCHK2-Thr68 and pCDC25C-Ser216 in breast cancer showed a positive linear correlation (p = 0.026). High expression of pCHK2-Thr68 was associated with decreased patient survival (p = 0.001), but was not an independent prognostic factor. Our results suggest that pCHK2-Thr68 and pCDC25C-Ser216 play important roles in breast cancer and may be potential treatment targets.

Phosphorylated-p38 mitogen-activated protein kinase expression is associated with clinical factors in invasive breast cancer.

PURPOSE: P38 mitogen-activated protein kinases (MAPK) level is an important prognostic factor in breast cancer. This study was performed to detect the expressions of P-p38 MAPK expression in breast cancer and explore their correlations with clinicopathological factors. EXPERIMENTAL DESIGN: Tumor samples from 355 Chinese patients diagnosed with invasive breast cancer and adjacent non-cancerous tissue were collected between 2003 and 2010. The expression of P-p38 MAPK was analyzed using immunohistochemical staining. The correlations between P-p38 MAPK expression and clinicopathological findings including age, AJCC Stage, Histologic characters, ER, PR, and HER2 were analyzed using the parametric correlation method. P-p38 MAPK was selected as dependent variable to perform multivariate analysis respectively at last. RESULTS: Overall, 161 (45 %) and 183 (52 %) of the 355 specimens showed positive P-p38 MAPK staining in the cytoplasm and nucleus respectively, which were significant higher than that in the adjacent non-cancerous tissues in both the cytoplasm and the nucleus. High P-p38 MAPK expression of cytoplasm and nucleus were both associated with positive PR status in luminal A/B type of breast cancer, and were both associated with positive HER2 status in HER2-positive type of breast cancer. The result of multivariate analysis demonstrated that HER2 and PR were both significantly association with P-p38 MAPK expression of cytoplasm and nucleus. CONCLUSIONS: Our study suggests that P-p38 MAPK expression were significantly associated with clinicopathological factors and PR/HER2 might association with phosphorylation of p38 MAPK in different types of breast cancer.

Quantitative assessment of the association between XRCC1 Arg399Gln and Arg194Trp polymorphisms and risk of cutaneous melanoma.

Accumulating evidence has suggested that the XRCC1 Arg399Gln and Arg194Trp polymorphisms might be related to cutaneous melanoma susceptibility. However, epidemiologic findings have been inconsistent. We have assessed reported studies by meta-analysis to perform a more precise estimation of the association between the XRCC1 two polymorphisms (Arg399Gln, Arg194Trp) and risk of cutaneous melanoma. A total of seven eligible articles were selected for this meta-analysis, including 3454 cases and 3811 controls for the XRCC1 Arg399Gln polymorphism and 1256 cases and 1575 controls for the XRCC1 Arg194Trp polymorphism. Overall, no significant associations were found in all genetic models when the studies were pooled into the meta-analysis for the Arg399Gln and Arg194Trp polymorphisms. When stratified by source of control, significant associations were found for the Arg399Gln polymorphism in the population-based subgroup under AA versus GG [odds ratio (OR)=1.43, 95% confidence interval (CI)=1.08-1.88]; the dominant model AA/GA versus GG (OR=1.25, 95% CI=1.04-1.51); and the recessive model AA versus GA/GG (OR=1.31, 95% CI=1.01-1.68). No significant associations were found for the Arg194Trp polymorphism in the subgroup analysis. This meta-analysis suggested that the XRCC1 Arg399Gln polymorphism was a risk factor for cutaneous melanoma in population-based subgroup.

Association between the CYP1A2 rs762551 Polymorphism and Bladder Cancer Susceptibility: a Meta-Analysis Based on Case-Control Studies.

BACKGROUND: Previous studies evaluated associations between the CYP1A2 rs762551 polymorphism and bladder cancer risk. However, the results were inconsistent. We therefore performed a meta-analysis of the published case-control studies to assess in detail the association between CYP1A2 rs762551 polymorphism and bladder cancer risk. MATERIALS AND METHODS: PubMed, Embase and Web of Science were searched to identify relevant studies and the pooled odds ratio (OR) and 95 % confidence interval (95%CI) were calculated. RESULTS: A total of seven articles including 3,013 cases and 2,771 controls were finally included. Overall, a significant association was found between the CYP1A2 rs762551 polymorphism and bladder cancer susceptibility for CC vs AA (OR=0.82, 95% CI=0.69~0.99), but no significant associations were found for the other three models (AC vs AA: OR=0.91, 95% CI=0.81~1.02; the dominant model: OR=0.90, 95% CI=0.80~1.00; the recessive model: OR=0.84, 95% CI =0.72~1.00). In the subgroup analysis by ethnicity, we detected significant associations between the CYP1A2 rs762551 polymorphism and bladder cancer susceptibility for GA vs GG (OR = 0.78, 95% CI =0.64~0.96) and for the recessive model (OR=0.80, 95% CI=0.66~0.96) in Caucasians, but not for Asians. CONCLUSIONS: The results from the meta-analysis suggested that the CYP1A2 rs762551 polymorphism is a protective factor for bladder cancer, especially in Caucasians.

A patient with a large intrathoracic malignant schwannoma who showed a complete clinical response to rAd-p53-combined with radiotherapy.

The prognosis of postoperatively recurred malignant schwannoma is poor and there is no effective treatment. We had a patient who was found to have a large intrathoracic tumor 1 year after surgery and could not tolerate an operation for the second time. We then decided to evaluate the synergistic effect of recombinant adenovirus-p53 (rAd-p53) combined with radiotherapy for the patient. rAd-p53 was injected intratumorally twice a week before radiotherapy, a total of 10 times, over a course of treatment. Radiotherapy then followed gene therapy at five fractions a week for 5 weeks, with a total dosage of 80.6 Gy/31f in the center part of the tumor and 62 Gy/31f in other locations. The pathological diagnosis of malignant schwannoma indicated that the p53 expression was strongly positive and vascular endothelial growth factor and Bcl-2 were positive before treatment on protein immunohistochemical staining. After treatment, the diameter of the tumor was noticeably reduced and the center part of the tumor presented as a fluid anechoic area and cavities on computed tomographic scanning. The result of the puncture biopsy showed that there were many fibronecrotic tissues and no significant tumor cells. The p53 expression was weakly positive, Vascular endothelial growth factor was negative, and Bcl-2 was weakly positive after treatment on protein immunohistochemical staining.

Genetic Association between the XPG Asp1104His Polymorphism and Head and Neck Cancer Susceptibility: Evidence Based on a Meta-Analysis.

BACKGROUND: Previous studies evaluating the association between the xeroderma pigmentosum group G (XPG) Asp1104His polymorphism and head and neck cancer susceptibility have proven controversial. This meta-analysis of the literature was performed to obtain a more precise estimation of the relationship. MATERIALS AND METHODS: We systematically searched PubMed, Embase and Web of Science with a time limit of Dec 18, 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of any association. RESULTS: We performed a meta-analysis of eight published case-control studies, including 3,621 cases and 5,475 controls. Overall, no significant association was found between the XPG Asp1104His polymorphism and head and neck cancer susceptibility under all genetic models. In the subgroup analysis by ethnicity, the XPG Asp1104His polymorphism had statistically significant association with elevated head and neck cancer risk under CC vs GG (OR=1.24, 95% CI=1.00~1.54) and the recessive model (OR=1.22, 95%CI=1.01~1.46) in Asian populations. A similar result was found under CC vs GG (OR =1.22, 95%CI =1.01~1.47) in the population based subgroup by source of control. When performed by tumor site, the XPG Asp1104His polymorphism had statistically significant association with elevated laryngeal cancer under all genetic models (CC vs GG: OR=1.59, 95% CI=1.16~2.19; GC vs GG: OR=1.38, 95%CI=1.10~1.72; dominant model: OR=1.42, 95% CI=1.15~1.74; recessive model: OR=1.36, 95% CI=1.02~1.81). CONCLUSIONS: This meta-analysis suggested that the XPG Asp1104His polymorphism is a risk factor for head and neck cancer susceptibility, especially for laryngeal cancer and in Asian populations.

Dosimetric Evaluation of Different Intensity-Modulated Radiotherapy Techniques for Breast Cancer After Conservative Surgery.

Intensity-modulated radiotherapy (IMRT) potentially leads to a more favorite dose distribution compared to 3-dimensional or conventional tangential radiotherapy (RT) for breast cancer after conservative surgery or mastectomy. The aim of this study was to compare dosimetric parameters of the planning target volume (PTV) and organs at risk (OARs) among helical tomotherapy (HT), inverse-planned IMRT (IP-IMRT), and forward-planned field in field (FP-FIF) IMRT techniques after breast-conserving surgery. Computed tomography scans from 20 patients (12 left sided and 8 right sided) previously treated with T1N0 carcinoma were selected for this dosimetric planning study. We designed HT, IP-IMRT, and FP-FIF plans for each patient. Plans were compared according to dose-volume histogram analysis in terms of PTV homogeneity and conformity indices (HI and CI) as well as OARs dose and volume parameters. Both HI and CI of the PTV showed statistically significant difference among IP-IMRT, FP-FIF, and HT with those of HT were best (P < .05). Compared to FP-FIF, IP-IMRT showed smaller exposed volumes of ipsilateral lung, heart, contralateral lung, and breast, while HT indicated smaller exposed volumes of ipsilateral lung but larger exposed volumes of contralateral lung and breast as well as heart. In addition, HT demonstrated an increase in exposed volume of ipsilateral lung (except for fraction of lung volume receiving >30 Gy and 20 Gy), heart, contralateral lung, and breast compared with IP-IMRT. For breast cancer radiotherapy (RT) after conservative surgery, HT provides better dose homogeneity and conformity of PTV compared to IP-IMRT and FP-FIF techniques, especially for patients with supraclavicular lymph nodes involved. Meanwhile, HT decreases the OAR volumes receiving higher doses with an increase in the volumes receiving low doses, which is known to lead to an increased rate of radiation-induced secondary malignancies. Hence, composite factors including dosimetric advantage, clinical effect, and economic burden should be taken into comprehensive consideration when choosing an RT technique in clinical practice.