Automatic tumor segmentation and metachronous single-organ metastasis prediction of nasopharyngeal carcinoma patients based on multi-sequence magnetic resonance imaging.

Background: Distant metastases is the main failure mode of nasopharyngeal carcinoma. However, early prediction of distant metastases in NPC is extremely challenging. Deep learning has made great progress in recent years. Relying on the rich data features of radiomics and the advantages of deep learning in image representation and intelligent learning, this study intends to explore and construct the metachronous single-organ metastases (MSOM) based on multimodal magnetic resonance imaging. Patients and methods: The magnetic resonance imaging data of 186 patients with nasopharyngeal carcinoma before treatment were collected, and the gross tumor volume (GTV) and metastatic lymph nodes (GTVln) prior to treatment were defined on T1WI, T2WI, and CE-T1WI. After image normalization, the deep learning platform Python (version 3.9.12) was used in Ubuntu 20.04.1 LTS to construct automatic tumor detection and the MSOM prediction model. Results: There were 85 of 186 patients who had MSOM (including 32 liver metastases, 25 lung metastases, and 28 bone metastases). The median time to MSOM was 13 months after treatment (7-36 months). The patients were randomly assigned to the training set (N = 140) and validation set (N = 46). By comparison, we found that the overall performance of the automatic tumor detection model based on CE-T1WI was the best (6). The performance of automatic detection for primary tumor (GTV) and lymph node gross tumor volume (GTVln) based on the CE-T1WI model was better than that of models based on T1WI and T2WI (AP@0.5 is 59.6 and 55.6). The prediction model based on CE-T1WI for MSOM prediction achieved the best overall performance, and it obtained the largest AUC value (AUC = 0.733) in the validation set. The precision, recall, precision, and AUC of the prediction model based on CE-T1WI are 0.727, 0.533, 0.730, and 0.733 (95% CI 0.557-0.909), respectively. When clinical data were added to the deep learning prediction model, a better performance of the model could be obtained; the AUC of the integrated model based on T2WI, T1WI, and CE-T1WI were 0.719, 0.738, and 0.775, respectively. By comparing the 3-year survival of high-risk and low-risk patients based on the fusion model, we found that the 3-year DMFS of low and high MSOM risk patients were 95% and 11.4%, respectively (p < 0.001). Conclusion: The intelligent prediction model based on magnetic resonance imaging alone or combined with clinical data achieves excellent performance in automatic tumor detection and MSOM prediction for NPC patients and is worthy of clinical application.

FBXL2 counteracts Grp94 to destabilize EGFR and inhibit EGFR-driven NSCLC growth.

Abnormal activation of epidermal growth factor receptor (EGFR) drives non-small cell lung cancer (NSCLC) development. EGFR mutations-mediated resistance to tyrosine-kinase inhibitors (TKIs) is a major hurdle for NSCLC treatment. Here, we show that F-box protein FBXL2 targets EGFR and EGFR TKI-resistant mutants for proteasome-mediated degradation, resulting in suppression of EGFR-driven NSCLC growth. Reduced FBXL2 expression is associated with poor clinical outcomes of NSCLC patients. Furthermore, we show that glucose-regulated protein 94 (Grp94) protects EGFR from degradation via blockage of FBXL2 binding to EGFR. Moreover, we have identified nebivolol, a clinically used small molecule inhibitor, that can upregulate FBXL2 expression to inhibit EGFR-driven NSCLC growth. Nebivolol in combination with osimertinib or Grp94-inhibitor-1 exhibits strong inhibitory effects on osimertinib-resistant NSCLC. Together, this study demonstrates that the FBXL2-Grp94-EGFR axis plays a critical role in NSCLC development and suggests that targeting FBXL2-Grp94 to destabilize EGFR may represent a putative therapeutic strategy for TKI-resistant NSCLC.

Transcriptional suppression of AMPKα1 promotes breast cancer metastasis upon oncogene activation.

AMP-activated protein kinase (AMPK) functions as an energy sensor and is pivotal in maintaining cellular metabolic homeostasis. Numerous studies have shown that down-regulation of AMPK kinase activity or protein stability not only lead to abnormality of metabolism but also contribute to tumor development. However, whether transcription regulation of AMPK plays a critical role in cancer metastasis remains unknown. In this study, we demonstrate that AMPKα1 expression is down-regulated in advanced human breast cancer and is associated with poor clinical outcomes. Transcription of AMPKα1 is inhibited on activation of PI3K and HER2 through ΔNp63α. Ablation of AMPKα1 expression or inhibition of AMPK kinase activity leads to disruption of E-cadherin-mediated cell-cell adhesion in vitro and increased tumor metastasis in vivo. Furthermore, restoration of AMPKα1 expression significantly rescues PI3K/HER2-induced disruption of cell-cell adhesion, cell invasion, and cancer metastasis. Together, these results demonstrate that the transcription control is another layer of AMPK regulation and suggest a critical role for AMPK in regulating cell-cell adhesion and cancer metastasis.

Automatic segmentation of cardiac substructures from noncontrast CT images: accurate enough for dosimetric analysis?

PURPOSE: We evaluated the feasibility of using an automatic segmentation tool to delineate cardiac substructures from noncontrast computed tomography (CT) images for cardiac dosimetry and toxicity analyses for patients with nonsmall cell lung cancer (NSCLC) after radiotherapy. MATERIAL AND METHODS: We used an in-house developed multi-atlas segmentation tool to delineate 11cardiac substructures, including the whole heart, four heart chambers, and six greater vessels, automatically from the averaged 4D-CT planning images of 49 patients with NSCLC. Two experienced radiation oncologists edited the auto-segmented contours. Times for automatic segmentation and modification were recorded. The modified contours were compared with the auto-segmented contours in terms of Dice similarity coefficient (DSC) and mean surface distance (MSD) to evaluate the extent of modification. Differences in dose-volume histogram (DVH) characteristics were also evaluated for the modified versus auto-segmented contours. RESULTS: The mean automatic segmentation time for all 11 structures was 7-9 min. For the 49 patients, the mean DSC values (±SD) ranged from .73 ± .08 to .95 ± .04, and the mean MSD values ranged from 1.3 ± .6 mm to 2.9 ± 5.1 mm. Overall, the modifications were small; the largest modifications were in the pulmonary vein and the inferior vena cava. The heart V30 (volume receiving dose ≥30 Gy) and the mean dose to the whole heart and the four heart chambers were not different for the modified versus the auto-segmented contours based on the statistically significant condition of p < .05. Also, the maximum dose to the great vessels was no different except for the pulmonary vein. CONCLUSIONS: Automatic segmentation of cardiac substructures did not require substantial modifications. Dosimetric evaluation showed no significant difference between the auto-segmented and modified contours for most structures, which suggests that the auto-segmented contours can be used to study cardiac dose-responses in clinical practice.

Clinical characteristics and prognosis of primary Waldeyer's ring and lymph node diffuse large B-cell lymphoma in the rituximab era.

This study was to compare the clinical characteristics and prognosis of Waldeyer's ring diffuse large B-cell lymphoma (WR-DLBCL) and lymph node DLBCL (LN-DLBCL) in the rituximab era. Before propensity score-matched (PSM), WR-DLBCL group shows more favorable clinical characteristics than LN-DLBCL group. After PSM, there was no significant difference in the response rate and survivals between them. The 5-year PFS and OS rates were 65.0% and 78.6% for WR-DLBCL group, respectively, and 53.7% and 66.1% for LN-DLBCL group, respectively. In WR-DLBCL group, ECOG score, Ann Arbor stage, B symptoms and IPI were associated with poor PFS and OS. In LN-DLBCL group, ECOG score, Ann Arbor stage, LDH, and IPI were significant factors to PFS and OS. Multivariate analysis showed that Ann Arbor stage was the only significant factor to PFS for WR-DLBCL group, for LN-DLBCL group, Ann Arbor stage and IPI were independent factors to PFS, LDH was the only significant factor to OS. WR-DLBCL was associated with more favorable clinical characteristics compared with LN-DLBCL, whereas, WR involvement itself did not have a real favorable prognostic significance. The PFS and OS of DLBCL were largely dependent on other prognostic factors such as Ann Arbor stage, LDH or IPI.

Incidence and Predictors of Pericardial Effusion After Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer.

PURPOSE: Findings from Radiation Therapy Oncology Group (RTOG) 0617 suggested that collateral radiation to the heart may contribute to early death in patients receiving chemoradiation therapy for non-small cell lung cancer (NSCLC); however, reports of cardiac toxicity after thoracic radiation therapy (RT) remain limited. Because pericardial disease is the most common cardiac complication of thoracic RT, we investigated the incidence of and risk factors for pericardial effusion (PCE) in patients enrolled in a phase 2 prospective randomized study of intensity modulated RT versus proton therapy for locally advanced NSCLC. METHODS AND MATERIALS: From July 2009 through April 2014, 201 patients were prospectively treated with proton beam therapy or intensity modulated RT to 60 to 74 Gy with concurrent chemotherapy. The primary endpoint (grade ≥2 PCE) was diagnosed on review of follow-up images. Clinical characteristics and cardiac dose-volume parameters associated with PCE were identified via Cox proportional hazards modeling and recursive partitioning analysis of null Martingale residuals. Reproducibility was evaluated in a separate retrospective cohort of 301 patients. RESULTS: The cumulative incidence rates of PCE among patients in the trial were 31.4% at 1 year and 45.4% at 2 years, with a median time to PCE of 8.9 months. Several cardiac dose-volume parameters (eg, V20 [volume receiving ≥20 Gy] to V65 [volume receiving ≥65 Gy]) predicted PCE, but heart volume receiving ≥35 Gy (HV35) was the most strongly associated, with a cutoff volume of 10%. On multivariate analysis, HV35 >10% independently predicted PCE (hazard ratio [HR], 2.14; P=.002), a finding that maintained reproducibility in the retrospective validation cohort. Other factors associated with PCE included receipt of adjuvant chemotherapy (HR, 2.82; P<.001) and prior cardiac disease (HR, 1.68; P=.020). CONCLUSIONS: PCE was common after RT for NSCLC, occurring in nearly half of patients even after moderate radiation doses to the heart. Adjuvant chemotherapy may increase the risk of PCE, and HV35 >10% may identify patients at risk of development of this cardiac toxicity.

Predicting brain metastases for non-small cell lung cancer based on magnetic resonance imaging.

In this study the relationship between brain structure and brain metastases (BM) occurrence was analyzed. A model for predicting the time of BM onset in patients with non-small cell lung cancer (NSCLC) was proposed. Twenty patients were used to develop the model, whereas the remaining 69 were used for independent validation and verification of the model. Magnetic resonance images were segmented into cerebrospinal fluid, gray matter (GM), and white matter using voxel-based morphometry. Automatic anatomic labeling template was used to extract 116 brain regions from the GM volume. The elapsed time between the MRI acquisitions and BM diagnosed was analyzed using the least absolute shrinkage and selection operator method. The model was validated using the leave-one-out cross validation (LOOCV) and permutation test. The GM volume of the extracted 11 regions of interest increased with the progression of BM from NSCLC. LOOCV test on the model indicated that the measured and predicted BM onset were highly correlated (r = 0.834, P = 0.0000). For the 69 independent validating patients, accuracy, sensitivity, and specificity of the model for predicting BM occurrence were 70, 75, and 66%, respectively, in 6 months and 74, 82, and 60%, respectively, in 1 year. The extracted brain GM volumes and interval times for BM occurrence were correlated. The established model based on MRI data may reliably predict BM in 6 months or 1 year. Further studies with larger sample size are needed to validate the findings in a clinical setting.

Incidence of small lymph node metastases in patients with nasopharyngeal carcinoma: Clinical implications for prognosis and treatment.

BACKGROUND: Patients with nasopharyngeal carcinoma (NPC) often present small lymph nodes. The purpose of this study was to determine the prognostic impact on local recurrence of small lymph nodes, defined as smaller than 10 mm in greatest diameter. METHODS: Consecutive patients treated by intensity-modulated radiotherapy (IMRT) for pathologically confirmed NPC were analyzed retrospectively. Those without small lymph nodes were excluded from the study. From January 2005 to January 2011, 275 patients with NPC represented with 2722 small lymph nodes, which were analyzed. Small lymph node axial diameter was measured using CT/MRI before radiotherapy (RT), at 50 Gy, and 6 months after the end of RT. The dose received by the small lymph nodes and the changes in lymph node diameter were recorded. Clinical endpoints were overall survival (OS), locoregional control, disease-specific survival (DSS), and distant metastasis-free survival. Median follow-up time was 55 months (range, 5-96 months). RESULTS: Patients were grouped according to the dose received by the small lymph nodes and the number of small lymph nodes. Only 27 patients (9.8%) had a decrease ≥50% in the small lymph node diameter at 50 Gy and 53 patients (19.3%) had a decrease ≥50% at 6 months after RT. The 5-year locoregional control, distant metastasis-free survival, DSS, and OS were 93.5%, 85.2%, 88.8%, and 87.0%, respectively. Multivariate analyses showed that T classification and N classification are independent prognostic factors for OS. However, the dose received and the numbers of small lymph nodes were not statistically associated with any of the survival endpoints. CONCLUSION: In the IMRT era, N classification remains an independent prognostic factor in NPC. However, the incidence of small lymph nodes is not a significant prognostic factor in patients with NPC. The presence of small lymph nodes should not influence the nodal contouring or the dose delivered to nodal areas. © 2016 Wiley Periodicals, Inc. Head Neck 39: 305-310, 2017.

Cervical nodal necrosis is an independent survival predictor in nasopharyngeal carcinoma: an observational cohort study.

PURPOSE: Most nasopharyngeal carcinoma (NPC) patients present with locoregionally advanced disease at the time of diagnosis; however, there is a lack of consensus on specific prognostic factors potentially improving overall survival, especially in late-stage disease. Herein, we conducted a retrospective study to evaluate various potential prognostic factors in order to provide useful information for clinical treatment of T3/T4-stage NPC. PATIENTS AND METHODS: A total of 189 previously untreated NPC patients were enrolled in the current study. All patients received intensity-modulated radiotherapy. Survival, death, relapse-free survival (both local and regional), and metastasis were recorded during follow-up. Factors affecting patient survival were assessed by using univariate and multivariate analyses. RESULTS: The median follow-up time was 69 months. The 5-year local-regional recurrence-free survival, distant metastasis-free survival, progression-free survival (PFS), and overall survival (OS) of the entire group were 89.8%, 71.5%, 66.3%, and 68.9%, respectively. Univariate analysis revealed significant differences in the 5-year PFS (58.5% vs 72.5%, P=0.015) and OS (59.5% vs 75.8%, P=0.033) rates of patients with and without cervical nodal necrosis (CNN). Subgroup analyses revealed that CNN was associated with poorer distant metastasis-free survival and PFS among patients with N2 stage (P=0.046 and P=0.005) and with poorer PFS among patients with T3 or III stage (all P=0.022). Multivariate analysis revealed CNN to be an independent prognostic factor for PFS and OS (PFS: adjusted hazard ratio, 1.860; 95% CI: 1.134-3.051; P=0.014; OS: adjusted hazard ratio, 1.754; 95% CI: 1.061-2.899; P=0.028). CONCLUSION: CNN is a potential independent negative prognostic factor in NPC patients. Our results suggest that stratification of NPC patients based on their CNN status should be considered as part of NPC disease management.

Dosimetric study for cervix carcinoma treatment using intensity modulated radiation therapy (IMRT) compensation based on 3D intracavitary brachytherapy technique.

PURPOSE: Intensity modulated radiation therapy (IMRT) compensation based on 3D high-dose-rate (HDR) intracavitary brachytherapy (ICBT) boost technique (ICBT + IMRT) has been used in our hospital for advanced cervix carcinoma patients. The purpose of this study was to compare the dosimetric results of the four different boost techniques (the conventional 2D HDR intracavitary brachytherapy [CICBT], 3D optimized HDR intracavitary brachytherapy [OICBT], and IMRT-alone with the applicator in situ). MATERIAL AND METHODS: For 30 patients with locally advanced cervical carcinoma, after the completion of external beam radiotherapy (EBRT) for whole pelvic irradiation 45 Gy/25 fractions, five fractions of ICBT + IMRT boost with 6 Gy/fractions for high risk clinical target volume (HRCTV), and 5 Gy/fractions for intermediate risk clinical target volume (IRCTV) were applied. Computed tomography (CT) and magnetic resonance imaging (MRI) scans were acquired using an in situ CT/MRI-compatible applicator. The gross tumor volume (GTV), the high/intermediate-risk clinical target volume (HRCTV/IRCTV), bladder, rectum, and sigmoid were contoured by CT scans. RESULTS: For ICBT + IMRT plan, values of D90, D100 of HRCTV, D90, D100, and V100 of IRCTV significantly increased (p < 0.05) in comparison to OICBT and CICBT. The D2cc values for bladder, rectum, and sigmoid were significantly lower than that of CICBT and IMRT alone. In all patients, the mean rectum V60 Gy values generated from ICBT + IMRT and OICBT techniques were very similar but for bladder and sigmoid, the V60 Gy values generated from ICBT + IMRT were higher than that of OICBT. For the ICBT + IMRT plan, the standard deviations (SD) of D90 and D2cc were found to be lower than other three treatment plans. CONCLUSIONS: The ICBT + IMRT technique not only provides good target coverage but also maintains low doses (D2cc) to the OAR. ICBT + IMRT is an optional technique to boost parametrial region or tumor of large size and irregular shape when intracavitary/interstitial brachytherapy cannot be used.

Effect of Kangfuxin Solution on Chemo/Radiotherapy-Induced Mucositis in Nasopharyngeal Carcinoma Patients: A Multicenter, Prospective Randomized Phase III Clinical Study.

Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group) or compound borax gargle (control group) during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and the Verbal Rating Scale (VRS). Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P = 0.01). The time to different grade of oral mucositis occurrence (grade 1, 2, or 3) was longer in test group (P < 0.01), and the accumulated radiation dose was also higher in test group comparing to the control group (P < 0.05). The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P < 0.01). No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application.

Prognostic value of CD44 expression in patients with hepatocellular carcinoma: meta-analysis.

BACKGROUND: CD44 has been reported to be involved with tumor growth and metastasis and has also been implicated as a CSC marker in hepatocellular carcinoma (HCC). However, the prognostic value of CD44 still remains controversial; hence, we investigated the correlation between CD44 and the clinicopathological features of HCC by meta-analysis. METHODS: Identification and review of publications assessing clinical or prognostic significance of CD44 expression in HCC until November 1, 2015. A meta-analysis was performed to clarify the association between CD44 expression and clinical outcomes. RESULTS: A total of 14 publications met the criteria and comprised 2235 cases. Analysis of these data showed that CD44 expression was not significantly associated with the tumor differentiation (OR 1.48, 95 % confidence interval [CI] 0.85-2.60, P = 0.17), AFP level of HCC patients (OR 0.83, 95 % CI 0.52-1.33, P = 0.45), or disease-free survival (relative risk [RR] 1.15, 95 % CI, 0.85-1.54; P = 0.36). However, in the identified studies, CD44 expression was highly correlated with tumor TNM classification (OR 2.38, 95 % CI 1.23-4.60; P = 0.01) and decreased overall survival (RR 1.49, 95 % CI, 1.26-1.76; P < 0.00001). CONCLUSIONS: This meta-analysis shows CD44 expression in HCC is connected with decreased overall and thus marks a worse prognosis.

Clinical Outcome and Prognostic Factors of Intensity-Modulated Radiotherapy for T4 Stage Nasopharyngeal Carcinoma.

Objective. To analyze the clinical outcomes and prognostic factors of intensity-modulated radiotherapy (IMRT) for T4 stage nasopharyngeal carcinoma (NPC). Methods. Between March 2005 and March 2010, 110 patients with T4 stage NPC without distant metastases were treated. All patients received IMRT. Induction and/or concurrent chemotherapy were given. 47 (42.7%) patients received IMRT replanning. Results. The 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 90.1%, 97.0%, 67.5%, 63.9%, and 64.5%, respectively. Eleven patients experienced local-regional failure and total distant metastasis occurred in 34 patients. 45 patients died and 26 patients died of distant metastasis alone. The 5-year LRFS rates were 97.7% and 83.8% for the patients that received and did not receive IMRT replanning, respectively (P = 0.023). Metastasis to the retropharyngeal lymph nodes (RLN) was associated with inferior 5-year OS rate (61.0% versus 91.7%, P = 0.034). The gross tumor volume of the right/left lymph nodes (GTVln) was an independent prognostic factor for DMFS (P = 0.006) and PFS (P = 0.018). GTVln was with marginal significance as the prognostic factor for OS (P = 0.050). Conclusion. IMRT provides excellent local-regional control for T4 stage NPC. Benefit of IMRT replanning may be associated with improvement in local control. Incorporating GTVln into the N staging system may provide better prognostic information.

CRTC2 and PROM1 expression in non-small cell lung cancer: analysis by Western blot and immunohistochemistry.

Accumulating evidence supports that genetic factors are another risk factors for lung cancer. Previously, we used whole exome sequencing with sanger sequencing to search for genetic-related mutations in one of four individuals from a pedigree with lung cancer history. Then, we used PCR-RFLP and direct-sequence in the sample size of 318 individuals with lung cancer (cases) and 272 controls. Recently, we detected two new genes including CRTC2 (CREB regulated transcription coactivator 2) and PROM1(human prominin-1,CD133). We investigated the CRTC2 mutation and PROM1 mutation of surgically resected NSCLC tissues (n=200). The presence or absence of CRTC2 and PROM1 mutation was analyzed by direct sequencing. The expression of CRTC2 and PROM1 was studied by western blot and immunohistochemical analysis of the lung cancer tissues which had the mutation of the two genes(cases), the samples without mutations(controls) and the normal lung tissue(controls). CRTC2 and PROM1 mutations in 5 NSCLC tissues and 3 NSCLC tissues out of the samples were identified. The positive results were closely correlated with clinicopathological features, such as male gender, adenocarcinoma, smoker status, and older age (≥55). We found that the CRTC2 and PROM1 expression were significantly higher in tissues of NSCLS with mutations than that without mutations and the normal lung tissue. The results imply that the high expression of CRTC2 and PROM1 may play an important role in the development and hereditary of NSCLC.

A dosimetry study precisely outlining the heart substructure of left breast cancer patients using intensity-modulated radiation therapy.

The purpose of this study was to evaluate the feasibility of delineating the substructure of the heart by using 64-slice spiral CT coronary angiography (CTA) in breast cancer patients who underwent left breast-conserving surgery, and to compare the dosimetric differences between the targets and organs at risk in the prone and supine positions in intensity-modulated radiation therapy (IMRT) planning. From January to December 2011, ten patients who underwent left breast-conserving surgery were enrolled in this study. CTA was performed in both the supine and prone positions during the simulation, and conventional scanning without CTA was performed at the same time. Image registration was performed for paired image series using a commercially available planning system. In a conventional image series, the clinical target volume (CTV) of the whole breast, planning target volume (PTV), bilateral lungs (L-Lung, R-Lung), spinal cord, contralateral breast (R-Breast), and heart were delineated. In the CTA image series, the left ventricular (LV) and left anterior descending coronary arteries (LAD) and the planning risk volume (LAD-PRV) of the LAD (LAD with a 1 cm margin) were outlined. For each patient, two separate IMRT plans were developed for the supine and prone positions. A total of 20 plans were generated. The following indicators were compared: Dmean and D95 for the PTV; Dmean, V5, and V20 for the left lung; Dmean, V10, V20, V25, V30, and V40 for the heart and its substructures (LAD-PRV, LV); Dmean and V5 for the right lung; and Dmax and Dmean for the right breast. Using CTA to delineate the substructures of the heart is simple and straightforward. Plans for both the prone and supine positions reached the prescribed dose for the PTV without significant differences. Dose distributions were acceptable for both the prone and supine positions. However, the LAD-PRV, LV, heart, and L-Lung received smaller doses in the prone position plans than in the supine position plans. The Dmean values reduced by 445.83 cGy (p = 0.043), 575.00 cGy (p = 0.003), 402.00 cGy (p = 0.039), and 553.33 cGy (p = 0.004) in the LAD-PRV, LV, heart, and L-Lung. In addition, the V25 lessened 12.54% (p = 0.042) and 8.70% (p = 0.019) in the LV and heart, while the V20 was decreased 8.57% (p = 0.042), 15.21% (p = 0.026), 12.59% (p = 0.011), and 10.62% (p = 0.006) in the LAD-PRV, LV, heart, and L-Lung, respectively. Similarly, the V10 and V30 were reduced by 28.31% (p = 0.029) and 5.54% (p = 0.034) in the heart, while the V5 was cut back 27.86% (p = 0.031) in the L-Lung. For most Asian women with average-sized breasts after breast conserving treatment (BCT), prone positioning during IMRT radiation will reduce the dose to the ipsilateral lung, heart, and substructures of the heart, which may reduce the incidence of cardiovascular events after radiotherapy more than radiation therapy performed in a supine position. Using CTA to delineate the substructures of the heart is easy and intuitive. It is cost-effective and highly recommended for breast cancer IMRT. However, the dose-volume limits of the heart substructures remain to be determined.

Identification and validation of PROM1 and CRTC2 mutations in lung cancer patients.

BACKGROUND: Genetic alterations could be responsible lung cancer, the leading cause of worldwide cancer death. METHODS: This study investigated gene mutations in a Han Chinese family of lung cancer using the whole genome exome sequencing and subsequent Sanger sequencing validation and then confirmed alteration of prominin 1(PROM1) and cyclic AMP-response element binding protein-regulated transcription co-activator2 (CRTC2) in blood samples of 343 sporadic lung cancer patients vs. 280 healthy controls as well as in 200 pairs of lung cancer and the corresponding normal tissues using PCR-restriction fragment length polymorphism and directed DNA sequencing of PCR products. RESULTS: The data showed PROM1 (p. S281R) and CRTC2 (p. R379C) mutations, in 5 and 2 cases of these 343 sporadic lung cancer patients, respectively. Notably, these mutations were absent in the healthy controls. Furthermore, in the 200 lung cancer and the matched normal tissues, PROM1 mutation occurred in 3 patients (i.e., one squamous cell carcinoma and two adenocarcinomas) with a mutation frequency of 1.5%, while CRTC2 mutation occurred in 5 patients (two squamous cell carcinomas and three adenocarcinomas) with a mutation frequency of 2.5%. CONCLUSIONS: The data from the current study demonstrated novel PROM1 and CRTC2 mutations, which could promote lung cancer development.

GSTP1 Ile105Val polymorphism and colorectal cancer risk: an updated analysis.

BACKGROUND: Many studies have investigated the association between the Glutathione S transferase-P1 (GSTP1) Ile105Val polymorphism and colorectal cancer (CRC) susceptibility, but the results were conflicting. The aim of this study is to quantitatively summarize the relationship between this polymorphism and CRC risk. METHODS: Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure (CNKI) and Chinese Biomedicine databases for studies published before December 2012. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for GSTP1 polymorphism and CRC were calculated in a fixed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. RESULTS: This meta-analysis included 29 case-control studies, which included 8160 CRC cases and 10,450 controls. Overall, the variant genotypes (ValVal and IleVal) of the Ile105Val were not associated with CRC risk when compared with the wild-type IleIle homozygote. Similarly, no associations were found in the dominant and recessive models. When stratifying for ethnicity, source of controls, study sample size and genotyping methods, no evidence of significant association was observed in any subgroup, except among those studies taking others as genotyping methods (recessive model, OR=0.71, 95%CI=0.52-0.96). Limiting the analysis to the studies within Hardy-Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study. CONCLUSION: This updated meta-analysis suggests that the GSTP1 Ile105Val polymorphism may not be associated with CRC risk, while the observed decrease in risk of CRC may be due to small-study bias.