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author:("Feng, goshen")
1.  Determining appropriate timing of adaptive radiation therapy for nasopharyngeal carcinoma during intensity-modulated radiation therapy 
To determine appropriate timing of an adaptive radiation therapy (ART) replan by evaluating anatomic and dosimetric changes of target volumes and organs at risk (OARs) during intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC).
Nineteen NPC patients were recruited. Each patient had repeat computed tomography (CT) scans after each five fractions and at treatment completion. Automatic re-contouring the targets and OARs by using deformable registration algorithm was conducted through CT-CT fusion. Anatomic changes were assessed by comparing the initial CT and repeated CT. Hybrid plans with re-contouring were generated and the dose-volume histograms (DVH) of the hybrid plan and the original plan were compared.
Progressive volume reductions in gross target volume for primary disease (GTVnx), gross target volume for involved lymph nodes (GTVnd), and parotids were observed over time. Comparing with the original plan, each hybrid plan had no significant difference in homogeneity index (HI) for all the targets. Some parameters for planning target volumes for primary disease and high-risk clinical target volume (PTVnx and PTV1, respectively) improved significantly, notably starting from the 10th fraction. These parameters included mean dose (Dmean), dose to 95 % of the volume (D95), percentage of the volume receiving 95 % of the prescription dose (V95), and conformity index (CI) for PTVnx, and Dmean, D95, and CI for PTV1. The dosimetric parameters for PTVnd remained the same in general except for D95 and V95 which had significant improvement at specific time points; whereas for PTV2, similar trend of dosimetric changes was also observed. Dose to some OARs increased significantly at some time points.
There were significant anatomic and dosimetric changes in the targets and OARs. The target dose coverage in the hybrid plans did not get worse, but overdose occurred in some critical structures. Significant dosimetric changes should be considered as a trigger point at which ART replanning is indicated. D95/V95/CI for PTV2, Dmax for the brain stem, spinal cord, right eyeball and left lens, and Dmean/V30 for the parotids and glottis were taken into account for predicting the need for ART. Two replans at the 5th and 15th fractions were suggested.
PMCID: PMC4573680  PMID: 26377685
2.  The expression of microRNA-375 in plasma and tissue is matched in human colorectal cancer 
BMC Cancer  2014;14:714.
MicroRNAs (miRNAs) offer great potential as cancer biomarkers. The importance of miRNAs profiling in tissue and body fluids in colorectal cancer (CRC) have been addressed respectively in many studies. The purpose of our study is to systematically assess the expression of miRNAs in cancer tissue and matched plasma samples and to evaluate their usefulness as minimally invasive diagnostic biomarkers for the detection of CRC.
The study was divided into two phases: firstly, qRT-PCR based TaqMan Low Density MiRNA Arrays (TLDAs) was used to screen the differentially expressed miRNAs in 6 plasma samples of CRC patients and 6 healthy controls. Secondly, marker validation by stem-loop reverse transcription real-time PCR using an independent set of paired cancer tissues (n = 88) and matched plasma samples (CRC, n = 88; control, n = 40). Correlation analysis was determined by Pearson’s test. Receiver operating characteristic curve analyses were applied to obtain diagnostic utility of the differentially expressed miRNAs. Target gene prediction and signal pathway analyses were used to predict the function of miRNAs.
TLDAs identified 42 miRNAs, which were differentially expressed in patients and healthy individuals. Five of them (miR-375, miR-150, miR-206, miR-125b and miR-126*) were chosen to be validated in plasma and tissue samples. The results indicated that for plasma sample, miR-375 (p < 0.0001) and miR-206 (p = 0.0002) were dysregulated and could discriminate CRC patients from healthy controls. For tissue samples, miR-375 (p < 0.0001), miR-150 (p < 0.0001), miR-125b (p = 0.0065) and miR-126*(p = 0.0009) were down-regulated. miR-375 was significantly down-regulated and positively correlated in both tissue and plasma samples (r = 0.4663, p = 0.0007). Gene ontology and signal pathway analyses showed that most of the target genes that were regulated by miR-375 were involved in some critical pathways in the development and progression of cancer.
Our results indicate that the down-regulation of miR-375 in plasma and tissue is matched in CRC. Moreover, bioinformatics prediction revealed miR-375 association with some critical signal pathways in the development and progression of CRC. Therefore, plasma miR-375 holds great promise to be an alternative tissue biomarker for CRC detection.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2407-14-714) contains supplementary material, which is available to authorized users.
PMCID: PMC4181388  PMID: 25255814
Colorectal cancer; MicroRNA; Plasma; Tissue; Biomarker; Diagnosis
3.  A prospective, randomized study on hepatotoxicity of anastrozole compared with tamoxifen in women with breast cancer 
Cancer Science  2014;105(9):1182-1188.
Tamoxifen and anastrozole are widely used as adjuvant treatment for early stage breast cancer, but their hepatotoxicity is not fully defined. We aimed to compare hepatotoxicity of anastrozole with tamoxifen in the adjuvant setting in postmenopausal breast cancer patients. Three hundred and fifty-three Chinese postmenopausal women with hormone receptor-positive early breast cancer were randomized to anastrozole or tamoxifen after optimal primary therapy. The primary end-point was fatty liver disease, defined as a liver–spleen ratio <0.9 as determined using a computed tomography scan. The secondary end-points included abnormal liver function and treatment failure during the 3-year follow up. The cumulative incidence of fatty liver disease after 3 years was lower in the anastrozole arm than that of tamoxifen (14.6% vs 41.1%, P < 0.0001; relative risk, 0.30; 95% CI, 0.21–0.45). However, there was no difference in the cumulative incidence of abnormal liver function (24.6% vs 24.7%, P = 0.61). Interestingly, a higher treatment failure rate was observed in the tamoxifen arm compared with anastrozole and median times to treatment failure were 15.1 months and 37.1 months, respectively (P < 0.0001; HR, 0.27; 95% CI, 0.20–0.37). The most commonly reported adverse events were ‘reproductive system disorders’ in the tamoxifen group (17.1%), and ‘musculoskeletal disorders’ in the anastrozole group (14.6%). Postmenopausal women with hormone receptor-positive breast cancer receiving adjuvant anastrozole displayed less fatty liver disease, suggesting that this drug had a more favorable hepatic safety profile than tamoxifen and may be preferred for patients with potential hepatic dysfunction.
PMCID: PMC4462391  PMID: 24975596
Anastrozole; breast cancer; clinical trial; fatty liver disease; hepatotoxicity; tamoxifen
4.  Radiation dose to the brachial plexus in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy: An increased risk of an excessive dose to the brachial plexus adjacent to gross nodal disease 
This retrospective study aimed to evaluate the dose to the brachial plexus in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Twenty-eight patients were selected and the brachial plexus was delineated retrospectively. Brachial plexus adjacent/not adjacent to nodes were defined and abbreviated as BPAN and BPNAN, respectively. Dose distribution was recalculated and a dose-volume histogram was generated based on the original treatment plan. The maximum dose to the left brachial plexus was 59.12–78.47 Gy, and the percentage of patients receiving the maximum dose exceeding 60, 66 and 70 Gy was 96.4, 57.1 and 25.0%, respectively; the maximum dose to the right brachial plexus was 59.74–80.31 Gy, and the percentage of patients exposed to a maximum dose exceeding 60, 66 and 70 Gy was 96.4, 64.3 and 39.3%, respectively. For the left brachial plexus, the maximum doses to the BPANs and the BPNANs were 72.84±3.91 and 64.81±3.47 Gy, respectively (p<0.001). For the right brachial plexus, the maximum doses to the BPANs and the BPNANs were 72.91±4.74 and 64.91±3.52 Gy, respectively (p<0.001). The difference between the left BPANs and the left BPNANs was statistically significant not only for V60 (3.60 vs. 1.01 cm3, p=0.028) but also for V66 (1.26 vs. 0.11 cm3, p=0.046). There were significant differences in V60 (3.68 vs. 1.16 cm3, p<0.001) and V66 (1.83 vs. 1.23 cm3, p=0.012) between the right BPANs and the right BPNANs. In conclusion, a large proportion of patients were exposed to the maximum dose to the brachial plexus exceeding the Radiation Therapy Oncology Group-recommended restraints when the brachial plexus was not outlined. The BPANs are at a significantly higher risk of receiving an excessive radiation dose when compared to the BPNANs. A further study is underway to test whether brachial plexus contouring assists in the dose reduction to the brachial plexus for IMRT optimization.
PMCID: PMC3439114  PMID: 22970028
brachial plexus; nasopharyngeal carcinoma; intensity-modulated radiation therapy; dose distribution
5.  The changes of Th17 cells and the related cytokines in the progression of human colorectal cancers 
BMC Cancer  2012;12:418.
The role of Th17 cells in colorectal tumorigenesis and development still remains unclear, despite the fact that it has been established in the pathogenesis of autoimmune diseases.
We first analyzed Th17 cells and Treg cells using flow cytometry in the circulation of colorectal adenoma (CRA) and colorectal carcinoma (CRC) patients and healthy controls, and the frequency of Th17 cells in peripheral blood mononuclear cells (PBMCs) stimulated by anti-CD3 plus anti-CD28 and treated by IL-1β, IL-6, and TGF-β in different concentrations. We then detected cytokines IL-1β, IL-6, IL-17A, IL-21, IL-23 or TGF-β by ELISA in sera and supernatants from both normal and tumor tissues cultured ex vivo.
It was found that the percentage of Th17 and Treg cells increased in the circulation of both CRA and CRC patients; the increase of Th17 cells in the circulation occurred in early stages, whereas the increase of Treg cells in the circulation and the increase of Th17 cells in tumor tissues occurred in advanced stages. The subsequent cytokine profiling showed that, along CRC progression, IL-1β, IL-17A and IL-23 underwent a similar change, while IL-6 in CRC exhibited an opposite change, with Th17 cells. In addition, high levels of TGF-β and IL-17A were detected in tumor tissues rather than in normal mucosa. The in vitro experiment further demonstrated that IL-1β, IL-6 or TGF-β modulated Th17 cell expansion in PBMC.
Our study reveals a unique change of Th17 cells, which is regulated possibly by IL-1β, IL-6 and TGF-β in the progression of CRC.
PMCID: PMC3488332  PMID: 22994684
Colorectal adenoma; Colorectal cancer; Th17 cells; Treg cells; Cytokines
6.  A Case Report of Scrotal Carcinoma and Review of the Literature 
Case Reports in Oncology  2012;5(2):434-438.
Scrotal carcinoma is a rare tumor. We report one case of such disease in a 60-year-old man presenting with an ulcerated-bleeding lesion on the left side of the scrotum and an enlarged lymph node in the left inguinal region. Biopsy of the ulcerated lesion found squamous cell carcinoma of the scrotum. He underwent initial tumor resection and left inguinal lymph node biopsy followed by postoperative concurrent chemoradiotherapy. Postoperative pathological examination confirmed well-differentiated squamous cell carcinoma of the scrotum and lymph node metastasis. Five months after the treatment, the size of the lymph node was dramatically decreased, with no signs of tumor progression. Surgical treatment combined with concurrent chemoradiotherapy may be an appropriate management approach to achieve palliative symptom relief for this disease.
PMCID: PMC3433011  PMID: 22949906
Scrotal carcinoma; Radiation therapy; Lymph node metastasis
7.  Interfractional and intrafractional errors assessed by daily cone-beam computed tomography in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy: a prospective study 
Journal of Radiation Research  2012;53(6):954-960.
This prospective study was to assess interfractional and intrafractional errors and to estimate appropriate margins for planning target volume (PTV) by using daily cone-beam computed tomography (CBCT) guidance in nasopharyngeal carcinoma (NPC). Daily pretreatment and post-treatment CBCT scans were acquired separately after initial patient setup and after the completion of each treatment fraction in 10 patients treated with IMRT. Online corrections were made before treatment if any translational setup error was found. Interfractional and intrafractional errors were recorded in the right–left (RL), superior–inferior (SI) and anterior–posterior (AP) directions. For the translational shifts, interfractional errors >2 mm occurred in 21.7% of measurements in the RL direction, 12.7% in the SI direction and 34.1% in the AP direction, respectively. Online correction resulted in 100% of residual errors ≤2 mm in the RL and SI directions, and 95.5% of residual errors ≤2 mm in the AP direction. No residual errors >3 mm occurred in the three directions. For the rotational shifts, a significant reduction was found in the magnitudes of residual errors compared with those of interfractional errors. A margin of 4.9 mm, 4.0 mm and 6.3 mm was required in the RL, SI and AP directions, respectively, when daily CBCT scans were not performed. With daily CBCT, the margins were reduced to 1.2 mm in all directions. In conclusion, daily CBCT guidance is an effective modality to improve the accuracy of IMRT for NPC. The online correction could result in a 70–81% reduction in margin size.
PMCID: PMC3483844  PMID: 22843373
nasopharyngeal carcinoma; intensity-modulated radiotherapy; cone-beam computed tomography; image-guided radiation therapy; setup error

Results 1-7 (7)