Cardiac Dose Predicts the Response to Concurrent Chemoradiotherapy in Esophageal Squamous Cell Carcinoma.

Definitive concurrent chemoradiation (CCRT) is the standard treatment for cervical esophageal cancer and non-surgical candidates. Initial treatment response affects survival; however, few validated markers are available for prediction. This study evaluated the clinical variables and chemoradiation parameters associated with treatment response. Between May 2010 and April 2016, 86 completed CCRT patients' clinical, dosimetric, and laboratory data at baseline and during treatment were collected. Cox regression analysis assessed the risk factors for overall survival (OS). A receiver operating characteristic curve with Youden's index was chosen to obtain the optimal cut-off value of each parameter. Treatment response was defined per Response Evaluation Criteria in Solid Tumors v.1.1 at the first post-CCRT computed tomography scan. Responders had complete and partial responses; non-responders had stable and progressive diseases. Logistic regression (LR) was used to evaluate the variables associated with responders. The Cox regression model confirmed the presence of responders (n = 50) vs. non-responders (n = 36) with a significant difference in OS. In multivariate LR, cardiac dose-volume received ≥10 Gy; the baseline hemoglobin level, highest neutrophil to lymphocyte ratio during CCRT, and cumulative cisplatin dose were significantly associated with the responders. The initial clinical treatment response significantly determines disease outcome. Cardiac irradiation may affect the treatment response.

Ag Nanoparticles Decorated CuO@RF Core-Shell Nanowires for High-Performance Surface-Enhanced Raman Spectroscopy Application.

Vertical-aligned CuO nanowires have been directly fabricated on Cu foil through a facile thermal oxidation process by a hotplate at 550 °C for 6 h under ambient conditions. The intermediate layer of resorcinol-formaldehyde (RF) and silver (Ag) nanoparticles can be sequentially deposited on Cu nanowires to form CuO@RF@Ag core-shell nanowires by a two-step wet chemical approach. The appropriate resorcinol weight and silver nitrate concentration can be favorable to grow the CuO@RF@Ag nanowires with higher surface-enhanced Raman scattering (SERS) enhancement for detecting rhodamine 6G (R6G) molecules. Compared with CuO@Ag nanowires grown by ion sputtering, CuO@RF@Ag nanowires exhibited a higher SERS enhancement factor of 5.33 × 108 and a lower detection limit (10-12 M) for detecting R6G molecules. This result is ascribed to the CuO@RF@Ag nanowires with higher-density hot spots and surface-active sites for enhanced high SERS enhancement, good reproducibility, and uniformity. Furthermore, the CuO@RF@Ag nanowires can also reveal a high-sensitivity SERS-active substrate for detecting amoxicillin (10-10 M) and 5-fluorouracil (10-7 M). CuO@RF@Ag nanowires exhibit a simple fabrication process, high SERS sensitivity, high reproducibility, high uniformity, and low detection limit, which are helpful for the practical application of SERS in different fields.

Optimization Temperature Programming of Microwave-Assisted Synthesis ZnO Nanoneedle Arrays for Optical and Surface-Enhanced Raman Scattering Applications.

This study used a rapid and simple microwave-assisted synthesis method to grow ZnO nanoneedle arrays on the silicon substrate with the ZnO seed layer. The effects of reaction temperature and time on the lengths of ZnO nanoneedle arrays were investigated. The appropriate temperature programming step can grow the longer ZnO nanoneedle arrays at the same reaction time (25 min), which is 2.08 times higher than without the temperature programming step. The geometry of the ZnO nanoneedle arrays features a gradual decrease from the Si substrate to the surface, which provides an excellent progressive refractive index between Si and air, resulting in excellent antireflection properties over an extensive wavelength range. In addition, the ZnO nanoneedle arrays exhibit a suitable structure for uniform deposition of Ag nanoparticles, which can provide three-dimensional hot spots and surface active sites, resulting in higher surface-enhanced Raman scattering (SERS) enhancement, high uniformity, high reusability, and low detection limit for R6G molecule. The ZnO/Ag nanoneedle arrays can also reveal a superior SERS-active substrate detecting amoxicillin (10-8 M). These results are promising for applying the SERS technique for rapid low-concentration determination in different fields.

Accuracy Evaluation of Collapsed Cone Convolution Superposition Algorithms for the Nasopharynx Interface in the Early Stage of Nasopharyngeal Carcinoma.

This study combined the use of radiation dosimeteric measurements and a custom-made anthropomorphic phantom in order to evaluate the accuracy of therapeutic dose calculations at the nasopharyngeal air-tissue interface. The doses at the nasopharyngeal air-tissue interface obtained utilizing the Pinnacle and TomoTherapy TPS, which are based on collapsed cone convolution superposition (CCCS) algorithms, were evaluated and measured under single 10 × 10 cm2, 2 × 2 cm2, two parallel opposed 2 × 2 cm2 and clinical fields for early stage of nasopharyngeal carcinoma by using EBT3, GR-200F, and TLD 100. At the air-tissue interface under a 10 × 10 cm2 field, the TPS dose calculation values were in good agreement with the dosimeter measurement with all differences within 3.5%. When measured the single field 2 × 2 cm2, the differences between the average dose were measured at the distal interface for EBT3, GR-200F, and TLD-100 and the calculation values were -15.8%, -16.4%, and -4.9%, respectively. When using the clinical techniques such as IMRT, VMAT, and tomotherapy, the measurement results at the interface for all three techniques did not imply under dose. Small-field sizes will lead to dose overestimation at the nasopharyngeal air-tissue interface due to electronic disequilibrium when using CCCS algorithms. However, under clinical applications of multiangle irradiation, the dose errors caused by this effect were not significant.

Fabrication of Three-Dimensional ZnO: Ga@ITO@Ag SERS-Active Substrate for Sensitive and Repeatable Detectability.

Vertically aligned ZnO: Ga nanotowers can be directly synthesized on a glass substrate with a ZnO seed film via the chemical bath method. A novel heterostructure of ZnO: Ga@ITO@Ag nanotowers was subsequently deposited in the ITO layer and Ag nanoparticles via the facile two-step ion-sputtering processes on the ZnO: Ga nanotowers. The appropriate ion-sputtering times of the ITO layer and Ag nanoparticles can benefit the fabrication of ZnO: Ga@ITO@Ag nanotowers with higher surface-enhanced Raman scattering (SERS) enhancement in detecting rhodamine 6G (R6G) molecules. Compared with ZnO: Ga@Ag nanotowers, ZnO: Ga@ITO@Ag nanotowers exhibited a high SERS enhancement factor of 2.25 × 108 and a lower detection limit (10-14 M) for detecting R6G molecules. In addition, the ITO layer used as an intermediate layer between ZnO: Ga nanotowers and Ag nanoparticles can improve SERS enhancement, sensitivity, uniformity, reusability, detection limit, and stability for detecting amoxicillin molecules. This phenomenon shall be ascribed to the ITO layer exhibiting a synergistic Raman enhancement effect through interfacial charge transfer for enhancing SERS activity. As a result, ZnO: Ga@ITO@Ag nanotowers can construct a three-dimensional SERS substrate for potential applications in environmentally friendly and cost-effective chemical or drug detection.

Low cardiac dose and neutrophil-to-lymphocyte ratio predict overall survival in inoperable esophageal squamous cell cancer patients after chemoradiotherapy.

We aimed to determine the prognostic significance of cardiac dose and hematological immunity parameters in esophageal cancer patients after concurrent chemoradiotherapy (CCRT). During 2010-2015, we identified 101 newly diagnosed esophageal squamous cell cancer patients who had completed definitive CCRT. Patients' clinical, dosimetric, and hematological data, including absolute neutrophil count, absolute lymphocyte count, and neutrophil-to-lymphocyte ratio (NLR), at baseline, during, and post-CCRT were analyzed. Cox proportional hazards were calculated to identify potential risk factors for overall survival (OS). Median OS was 13 months (95% confidence interval [CI]: 10.38-15.63). Univariate analysis revealed that male sex, poor performance status, advanced nodal stage, higher percentage of heart receiving 10 Gy (heart V10), and higher NLR (baseline and follow-up) were significantly associated with worse OS. In multivariate analysis, performance status (ECOG 0 & 1 vs. 2; hazard ratio [HR] 3.12, 95% CI 1.30-7.48), heart V10 (> 84% vs. ≤ 84%; HR 2.24, 95% CI 1.26-3.95), baseline NLR (> 3.56 vs. ≤ 3.56; HR 2.36, 95% CI 1.39-4.00), and follow-up NLR (> 7.4 vs. ≤ 7.4; HR 1.95, 95% CI 1.12-3.41) correlated with worse OS. Volume of low cardiac dose and NLR (baseline and follow-up) were associated with worse patient survival.

Technical Note: Radiotherapy dose characterization of gel dosimetry using shear wave elasticity imaging.

PURPOSE: Radiotherapy is an effective treatment for many types of cancer in clinical settings. Gel dosimetry has the potential to record three-dimensional (3D) dose distribution compared to a conventional ion chamber. As the elasticity of the gel is altered after irradiation due to gel polymerization, we aim to measure the dose recorded in gel dosimetry with ultrasonic shear wave elasticity imaging (SWEI), a nondestructive and quantitative elasticity imaging tool. METHODS: In this study, a cylindrical N-isopropylacrylamide (NIPAM) polymer gel with a diameter of 10 cm and a height of 10 cm and with cellulose as an ultrasonic scatterer was irradiated by a linear accelerator with the irradiation parameters of 6 MV x-ray, dose rate of 100 cGy/min and field size of 10  ×  20 mm2 . The six gel phantoms were irradiated with the dose of 0, 1, 3, 5, 8, or 10 Gy. The gel phantoms were measured with SWEI at 24, 36, and 48 h after x-ray irradiation. The two-dimensional (2D) shear wave velocity and Young's modulus maps corresponding to x-ray dose distribution were reconstructed following a time-of-flight reconstruction from a set of time-series displacement maps. The spatial resolution of the reconstructed SWEI image is ~1 mm. RESULTS: Our results show that the elastic modulus increases linearly as irradiation dose increases (R2  = 0.94 at 24 h, R2  = 0.98 at 36 h, R2  = 0.98 at 48 h), suggesting that the gel elasticity is highly associated with x-ray irradiation dose at 36 h post irradiation, and the dose resolution was 0.66 kPa/Gy. From the 3D elastic modulus maps, the dose distribution along the depth and lateral direction can be reflected in the NIPAM gel dosimetry using SWEI as well. CONCLUSIONS: In this study, the irradiated NIPAM gel phantom was quantitatively measured with SWEI for the first time to read the dose distribution recorded in the gel dosimetry. The results suggest that the gel elasticity is highly associated with x-ray irradiation dose. In the future, 2D/or 3D dose distribution from intensity modulated radiotherapy (IMRT) or other potential particle radiotherapy will be measured and reconstructed with SWEI and compared with the dose map from a treatment planning system (TPS) in the clinic.

Prognostic significance of lung radiation dose in patients with esophageal cancer treated with neoadjuvant chemoradiotherapy.

BACKGROUND: The prognostic significance of radiation dose to the lung or heart is unknown in esophageal cancer patients receiving neoadjuvant chemoradiotherapy followed by surgery (trimodal therapy). This study aimed to determine the association between lung and heart radiation dose volumes and prognosis of esophageal cancer after trimodal therapy. METHODS: This study reviewed 123 esophageal cancer patients treated with trimodal therapy in two tertiary institutions between 2010 and 2015. The dose-volume histogram parameter of Vx was defined as the percentage of total organ volume receiving a radiation dose of x (Gy) or more. Predictors of overall survival (OS) were identified using Cox regression models. Receiver-operating characteristic curves were used to select cut-off values for dose-volume. RESULTS: Median follow-up was 28.3 months (range: 4.7-92.8 months). Median OS and progression-free survival were 34.0 months (95% confidence interval [CI]: 27.4-40.6 months) and 24.8 months (95% CI, 18.9-30.7 months), respectively. Multivariate analyses showed that lung V20 (hazard ratio, 1.09; 95% CI: 1.04-1.14; p < 0.001) and lung V5 (hazard ratio, 1.02; 95% CI: 1.00-1.05; p = 0.03) were associated with OS when adjusting for surgical margin and pathological treatment response. The 5-year OS for patients with lung V20 ≤ 23% vs. patients with lung V20 > 23% was 54.4% vs. 5% (p < 0.001) whereas that for patients with lung V5 ≤ 56% vs. patients with lung V5 > 56% was 81.5% vs. 23.4% (p < 0.001). Mean heart dose showed no association with survival outcomes. CONCLUSIONS: Lung radiation dose was independently associated with survival outcomes in esophageal cancer patients treated with neoadjuvant chemoradiotherapy and surgery.

Three-dimensional dose comparison of flattening filter (FF) and flattening filter-free (FFF) radiation therapy by using NIPAM gel dosimetry.

Intensity-modulated radiotherapy and volumetric modulated arc therapy are modern radiation therapy technologies that can create the desired dose distribution by multileaf collimator movement and dose-rate control. However, the homogeneous dose delivery of small-field irradiation techniques shows disagreement with that of treatment planning system. The removal of the flattening filter by flattening filter free (FFF) beam irradiation increases dose conformity and further reduces treatment delivery time in radiosurgery. This study aims to investigate the dose distribution of FFF and flattened beams for small-field irradiation by using the 3D gel dosimeter. The N-isopropylacrylamide (NIPAM) polymer gel dosimeter was employed to record the 3D dose distribution. In addition, flattened and FFF beams were compared using the gamma evaluation technique. The use of an FFF accelerator resulted in excellent radiation treatments with short delivery times and low doses to normal tissues and organs. Results also showed that the passing rate increased with the decrease of field size (30 × 30, 20 × 20, and 10 × 10 mm2) at post-irradiation times of 24, 48, 72, and 96 h. The passing rates for each field size were retained at the same level when gamma criteria, namely, distance-to-agreement (DTA) = 3 mm/dose difference (DD) = 3%, were used. Nevertheless, the passing rates for each field size decreased slowly after 48 h when DTA = 2 mm/DD = 2%. The Wilcoxon signed-rank test was used to determine statistical difference with a significant level of p < 0.05. The passing rates of flattened and FFF beams showed no significant difference. The edge enhancement effect in the flattened beam was more evident than in the FFF beam. The 3D NIPAM gel dosimeter can be used for dose verification of small field for radiation therapy with high dose rate.

Is unenhanced 18F-FDG-PET/CT better than enhanced CT in the detection of retropharyngeal lymph node metastasis in nasopharyngeal carcinoma?

Positron-emission tomography/computed tomography (PET/CT) has been proposed as a means to enhance the pretreatment evaluation of cervical lymph node status in patients with nasopharyngeal carcinoma (NPC). We conducted a prospective study to compare PET/CT and enhanced CT for the detection of retropharyngeal lymph node (RLN) metastasis in NPC, and to ascertain the factors that affect its diagnostic performance. Our study population was made up of 33 patients-24 men and 9 women, aged 30 to 81 years (mean: 52)-with newly diagnosed NPC who had been treated over a 2-year period. All patients underwent enhanced CT first, followed by unenhanced 18F-fluorodeoxyglucose (FDG) PET/CT. The detection rate of RLN metastasis on PET/CT was significantly lower than that on enhanced CT (36.4 vs. 75.8%; p < 0.001). A total of 25 of 26 nodes with a discordant finding were negative on PET/CT; they included 13 metastatic lymph nodes with low FDG uptake, 9 that were located close to the primary tumor, 2 that were confluent RLNs, and 1 that was adjacent to the physiologic FDG-avid prevertebral muscle. The maximum standardized uptake value (SUVmax) of RLNs was positively correlated with the minimum axial diameter (r = 0.803, p < 0.001). The PET/CT detection rate was 0% for lymph nodes smaller than 5 mm, 9% for those 5 to 10 mm, and 73% for those 1 cm or larger. The detection rate of PET/CT at level C1 was significantly lower than that at C2 (22 vs. 67%; p = 0.035). We conclude that unenhanced PET/CT is markedly inferior to enhanced CT for detecting RLN metastasis in NPC, especially in lymph nodes with a minimum axial diameter of less than 1 cm and those in proximity to the primary tumor. Using enhanced CT in PET/CT is justified to improve the recognition of RLN metastasis in patients with NPC.

Colon cancer mesenchymal stem cells modulate the tumorigenicity of colon cancer through interleukin 6.

Multipotent mesenchymal stem cells (MSCs) have been isolated from several tumors and are implicated to play critical roles to increase malignant cell growth, invasion and metastasis. Here, we show that the MSC-like cells were isolated from human colon cancer tissues. These isolated hCC-MSCs (human colon cancer-derived mesenchymal stem cells) shared similar characteristic features with bone marrow-derived MSCs, which include cell morphology, surface antigens and specific gene expression. Additionally, the hCC-MSCs could differentiate into osteocytes or adipocytes under appropriate culture conditions. The conditioned medium collected from the cultured hCC-MSCs was shown to enhance the migration and invasive activity of HCT-116 colon cancer cells in vitro. Besides, transplantation of HCT-116 cells along with hCC-MSCs in nude mice increased the tumor growth and metastasis. Further study revealed that IL-6 present in the hCC-MSC-conditioned medium sufficiently induced the levels of Notch-1 and CD44 in HCT-116 and HT-29 cells, which contribute to enhance tumorigenic activity of HCT-116 and HT-29 cells. By using immunohistochemical staining, the intense co-expression of IL-6, Notch-1 and CD44 was predominantly detected in human colon cancer tissues. Taken together, our findings suggest the importance of the IL-6/Notch-1/CD44 signaling axis in the interaction between hCC-MSCs and colon cancer cells.

Chemotherapy with modified docetaxel, cisplatin, and 5-fluorouracil in patients with metastatic head and neck cancer.

INTRODUCTION: This retrospective study evaluates the efficacy of palliative chemotherapy with a modified docetaxel, cisplatin, 5-fluorouracil (5-FU; "TPF" regimen) regimen (mTPF; reduced doses of docetaxel, cisplatin, and 5-FU with reduction of intravenous 5-FU from 4 days to 2 days) in Asian patients with recurrent and metastatic squamous cell carcinoma of head and neck (HNSCC) after surgery and adjuvant chemoradiation. METHODS: The mTPF regimen was used in this study. Fifty-five patients (from January 2007 to October 2009) received docetaxel on day 1, followed by cisplatin and 5-FU administered continuous infusion on day 2 for another 48 hours every 3 weeks for three to six cycles. RESULTS: The disease control rate was 81%. The overall response rate was 56%. Five patients achieved complete remission; 26 patients had partial remission; 14 patients had stable disease. Ten patients had disease progression. The metastatic sites that responded well to mTPF regimen (either complete or partial remission) were: neck lymph node, lung, liver, and skin. The median follow-up was 15 months (range 1-28 months). The median overall survival was 10 months (range 2-28 months). The common nonhematological toxicity was alopecia and the most common hematological adverse event was neutropenia. Thirty-one patients (56%) had grade 3-4 neutropenia. CONCLUSION: The mTPF chemotherapy regimen is efficacious for the palliative treatment of recurrent and metastatic HNSCC in Asian patients.

Association of high levels of Jagged-1 and Notch-1 expression with poor prognosis in head and neck cancer.

BACKGROUND: The aim of this study was to evaluate the prognostic value of the Jagged-1/Notch-1 expression in patients with head and neck carcinoma and to examine the possible role of the Jagged-1/Notch-1 signaling in tumorigenesis. METHODS: Immunohistochemical staining was performed on 59 formalin-fixed, paraffin-embedded head and neck carcinoma surgical specimens for Jagged-1 and Notch-1 expression. The head and neck cancer cell line, Fadu, with or without ectopic expression of the intracellular domain of Notch-1 (NICD) was also used for examining the tumorigenic capacity in vitro and in vivo. RESULTS: The study included 59 patients with a median age of 54 years (range, 35-73 years). Patients harboring tumors with both high-level Jagged-1 (J1(Hi)) and high-level Notch-1 (N1(Hi)) had a worse overall survival than the patients only with J1(Hi) or N1(Hi) as well as the patients with low-level Jagged-1 and Notch-1 (J1(Lo)/N1(Lo)) (P < 0.001). The 5-year survival rate and the median survival time were 5% and 10.9 months for J1(Hi)/N1(Hi) patients, while they were 35.04% and 47.7 months for non-J1(Hi)/Ni(Hi) patients. Ectopic expression of the active Notch-1 (NICD) in Fadu cells greatly enhanced cell migration and invasiveness in vitro and tumorigenic capacity in vivo. CONCLUSIONS: High-level coexpression of Jagged-1 and Notch-1 is associated with poor overall survival in patients with head and neck cancer. Constitutive activation of the Notch signaling, which is possibly initiated by the direct interaction between Jagged-1 and Notch-1 in head and neck cancer, confers tumor cells with a more aggressive phenotype.

Quantitative ultrasound of the calcaneus in hemodialysis patients.

The aim of this study was to investigate the bone status of hemodialysis patients and identify factors that have influence on bone quality. Four hundred eighty-nine subjects (213 males and 276 females) on maintenance hemodialysis and 696 healthy subjects (309 men, 387 women) were enrolled in this study. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and quantitative ultrasound index (QUI) were assessed by quantitative ultrasound (QUS) at the right calcaneus in both groups. Serum levels of intact parathyroid (iPTH), total alkaline phosphatase (ALP), calcium and phosphate were measured to determine their influence on bone status in hemodialysis patients. All QUS parameters were significantly lower in hemodialysis patients than in controls (p < 0.0001). Stepwise multiple linear regression analysis in male patients indicated that age, weight, calcium-phosphate product and ALP were significant predictors of QUS parameters (adjusted R(2) = 0.15 in SOS; adjusted R(2) = 0.17 in BUA and QUI). In female patients, same findings including number of parity were observed in SOS only (adjusted R(2) = 0.25 in SOS). In postmenopausal patients, the duration of menopause was significant negatively correlated with all QUS parameters (p < 0.01). In conclusion, patients on maintenance hemodialysis had additional risk of bone loss. Advanced age, low body weight, high calcium-phosphate product and high ALP level were important risk factors for deterioration of bone quality.

Prognostic value of pretreatment CD44 mRNA in peripheral blood of patients with locally advanced head and neck cancer.

This study investigates the clinical significance of CD44 messenger RNA (mRNA) expression in the peripheral blood of patients with head and neck cancer. Real-time reverse transcriptase-polymerase chain reaction analysis was used to quantify CD44 mRNA levels in the peripheral blood of patients with locally advanced head and neck cancer. All patients were enrolled between January 2006 and December 2008 and had received chemotherapy/radiotherapy for their head and neck cancers. The pretreatment CD44 mRNA levels at a cutoff point of greater than fivefold were associated with an odds ratio of 12.5 for poor prognosis (95% CI, 3.9-40; p<0.001) and could predict poor treatment response in patients with locally advanced head and neck cancers. Larger prospective studies comparing the current assay with standardized methodologies are warranted.

Docetaxel, carboplatin and 5-fluorouracil (TCF) chemotherapy in patients with unresectable metastatic carcinoma of cervix.

OBJECTIVES: This retrospective study evaluates the efficacy and safety of chemotherapy with docetaxel, carboplatin and 5-FU (TCF) in patients with metastatic cervical carcinoma. METHODS: Between January 2006 and April 2007, 23 patients with metastatic cervical carcinoma were included in the study. Patients fulfilling the following criteria were enrolled: histologically confirmed metastatic cervical carcinoma; documented progressive disease (PD) after cisplatinum-based treatment if applicable; an Eastern Cooperative Oncology Group (ECOG) performance scale of 0-2; not candidates for local therapy; measurable metastatic lesions as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST); and adequate hematologic, hepatic, and renal functions. Treatment consisted of intravenous docetaxel at 60 mg/m(2) diluted in 500 ml 5% glucose administered over 1 h on day 1, followed by carboplatin (AUC of 5 or 6) given as a 1-h intravenous infusion delivered on day 2, followed by 5-FU at 500 mg/m(2) diluted in 500 ml normal saline continuously infusion for 24 h for 2 days on day 2. Chemotherapy was repeated every 21 days, and a total of 1-5 courses were performed. RESULTS: There were 3 (13%) complete responses; 4(17%) partial responses; 6 (26%) with stable disease, and 10 (43%) with disease progression. The overall response rate was 56%. After a median follow-up of 16 months, the median overall survival was 12 months. Neutropenia was the most severe toxicity. CONCLUSIONS: The combination of docetaxel, carboplatin and 5-fluorouracil (TCF) appears to have activity in metastatic cervical carcinoma with acceptable toxicity profile.

Prediction of outcome of patients with metastatic breast cancer: evaluation with prognostic factors and Nottingham prognostic index.

GOALS OF WORK: The purpose of this study is to analyze the survival rate of patients with metastatic breast cancer and to evaluate the outcome of these patients using prognostic factors and Nottingham prognostic index. MATERIALS AND METHODS: From February 1992 to August 2008, 135 patients with metastatic breast cancer were treated at the Changhua Christian Hospital. In these patients, we evaluated the significance of the following factors in predicting the survival rate after the occurrence of metastasis: age, initial stage at primary diagnosis, histological grade, Karnofsky performance status (KPS), estrogen receptor (ER), progesterone receptor status, human epidermoid growth factor receptor 2 overexpression status, number of axillary lymph node metastasis, history of adjuvant radiotherapy and/or chemotherapy, disease-free interval, status of local recurrence, status of various sites of distant metastases, number of distant metastases, and Nottingham prognostic index. MAIN RESULTS: The 1-, 2-, and 5-year survival rates were 53.3%, 25.2%, and 1.5%, respectively. In the univariate analysis, KPS, histological grade, ER status, initial stage at primary diagnosis, number of axillary lymph node metastasis, liver metastasis, disease-free interval, first-/second-/third-line chemotherapy for recurrence or metastasis, number of metastases, and Nottingham prognostic index had significant impact on survival. The median survival of patients determined as corresponding to Nottingham low-risk group, intermediate-risk group, and high-risk group was 29.3, 17.9, and 4.6 months, respectively. In our multivariate analysis, Karnofsky performance status (p = 0.030) and Nottingham prognostic index (p ≤ 0.0001) were significant prognostic factors for survival, while first-/second-/third-line chemotherapy for recurrence or metastasis (p = 0.002) was a significant predictor for the outcome of the treatment. CONCLUSIONS: The prognosis of patients with metastatic breast cancer is poor. In spite of the fact that many advances in treatment have been made, numerous additional questions have arisen; new drugs and therapeutic regimens are needed to improve the outcomes of patients, and further well-designed randomized trials are warranted.

Effect of cigarette smoking on bone mineral density in healthy Taiwanese middle-aged men.

The effect of cigarette smoking in relation to bone mineral density (BMD) remains inconclusive, especially in middle-aged men. This cross-sectional study was conducted to examine the effect of smoking on BMD in 837 healthy Taiwanese males (532 never-smokers, 258 current smokers, 47 former smokers; aged 46-64 yr), recruited at their routine health examination. Subjects with suspected conditions affecting bone metabolism or receiving any medications affecting bone metabolism were excluded. BMD of the lumbar spine (LSBMD) and femoral neck (FNBMD) was measured with dual-energy X-ray absorptiometry. After adjustment for confounding variables (age, weight, physical activity, alcohol consumption, and caffeine intake), we found that the mean value of LSBMD was significantly (2.9%) lower in current smoker compared with never-smokers (p=0.024), but no significant difference was observed in FNBMD. No statistically significant association was observed between former smokers and never-smokers in any of the BMD sites, indicating that quitting smoking did have a positive effect on bone density. Compared with never-smokers, current heavy smokers who consumed at least 20 cigarettes/d (n=94) had 3.8% lower LSBMD (p=0.04), but no significant difference was observed in FNBMD. In the correlation analysis, the duration of smoking was negatively associated with LSBMD (r=-0.166, p=0.004), but no association was shown in FNBMD. Our results suggested that both smoking status and duration of smoking were deleterious factors on the bone density of the lumbar spine, and the effect was cumulative with duration and quantity.

Prognostic factors affecting the outcome of brain metastases from breast cancer.

GOALS OF WORK: The purpose of this study is to analyze the overall survival rate of patients with brain metastases from breast cancer and to determine prognostic factors affecting outcomes of these patients. PATIENTS AND METHODS: From July 1988 to December 2004, 48 female patients with brain metastases from breast cancer underwent full-dose whole-brain radiotherapy (WBRT). In these patients we evaluated the significance of the following factors in predicting the survival rate after WBRT: age, extracranial metastases, number of brain metastases, total dose of WBRT, Karnofsky performance status (KPS), and Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class. RESULTS: The median overall survival rate was 7.3 months. The 1- and 2-year overall survival rates were 37 and 20%, respectively. In univariate analysis, KPS (p<0.0001), number of lesions of brain metastases (p=0.0149), age (p=0.0452), and RPA class (p<0.0001) were statistically significant prognostic factors for overall survival. In multivariate analysis, KPS (p<0.001) and number of brain metastases (p=0.039) were significant prognostic factors for overall survival. CONCLUSIONS: Survival of breast cancer patients with brain metastases treated with WBRT is poor. To improve survival, enrollment of more patients with brain metastases from breast cancer for prospective trials involving a multimodality approach that combines radiation and systemic therapies based on appropriate patient triage is warranted.