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This study explored which kinds of cancer are related to a higher incidence of subsequent myelodysplastic syndrome (MDS) after radiotherapy (RT) and chemotherapy (CT).We performed a nested case-control study by using data from the Taiwanese National Health Insurance (NHI) system. The case group included cancer patients who developed MDS. For the control group, 4 cancer patients without MDS were frequency-matched with each MDS case by age, sex, year of cancer diagnosis, and MDS index year. A multivariable logistic regression analysis was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated.Overall, cancer patients who received RT or CT exhibited secondary MDS more frequently than did those who did not (RT: OR = 1.53; 95% CI = 1.33-1.77; CT: OR = 1.51; 95% CI = 1.25-1.82). Analysis by cancer site showed that RT increased the risk of MDS for patients with stomach, colorectal, liver, breast, endometrial, prostate, and kidney cancers. By contrast, CT was more likely to increase the risk of MDS for patients with lung, endometrial, and cervical cancers. Further analysis revealed that RT and CT seemed to have a positive interaction. The major limitation of this study was the lack of certain essential data in the NHI Research Database, such as data regarding cancer stage and treatment dose details.This population-based nested case-control study determined that RT and CT predisposed patients in Taiwan to the development of MDS. This effect was more prominent when both modalities were used.

This study examined and analysed the relationship between the cost-effectiveness and outcome of radiotherapy for oesophageal cancer among hospitals with varying accreditation levels. We selected 428 oesophageal cancer patients from medical and non-medical centres using the National Health Insurance Research Database, which is maintained by the Taiwanese National Health Research Institutes, and compared their medical expenditure and the outcome of their radiotherapy treatment. In this study cohort of patients with oesophageal cancer, 278 patients were treated in medical centres (mean age: 60.1 years) and 150 patients were treated in non-medical centres (mean age: 62.0 years, P = 0.16). The medical centre group exhibited significantly lower medical expenses, mortality and risk of death compared with the non-medical centre group (adjusted hazard ratio = 1.38, 95% confidence interval = 1.11-1.71). Our study determined that radiotherapy for oesophageal cancer costs significantly less, and medical centres had lower mortality rates than non-medical centres. These findings could provide professional organisations and healthcare policy makers with essential information for allocation of resources., (© 2015 John Wiley & Sons Ltd.)

Objectives: This study investigates the relationship between current morphine use and the risk of pulmonary embolism (PE) development in deep vein thrombosis (DVT) patients., Methods: We conducted a population-based nested case-control retrospective analysis using the Longitudinal Health Insurance Database 2000 of Taiwan. A DVT cohort of 3668 patients with no history of PE from 1998 to 2010 and the other cohort of 174 patients who subsequently developed PE were evaluated. Morphine use was designated as 'current' if the prescription duration covered the index date or ended within 30 days before the index date. Logistic regression was used to estimate the odds ratios and 95% confidence intervals (CI), and the multivariable model was applied to control for age., Results: Compared with non-morphine users, DVT patients who received morphine within 30 days of the index date had a 4.54-fold (95% CI = 2.30-8.97) chance of developing PE. The risk of PE development increased with an increase in cumulative dosage and in the average dosage of morphine., Conclusion: The incidence of PE in DVT patients in Taiwan is associated with current morphine treatment (≤30 days) and is dependent on dosage., (© 2014 John Wiley & Sons Ltd.)

Although a relationship between hypertension and the development of renal cancer and other types of cancer have been proposed for decades, the results of epidemiologic studies remain inconclusive. This study was conducted to evaluate the association between hypertension and genitourinary and gynecologic cancers in Taiwan.In this study, we conducted a populated-based retrospective cohort study by using data from the Taiwanese National Health Insurance program. The study period was from 2000 to 2011, and the cohort comprised 111,704 insurants: 57,961 patients with hypertension and 53,743 patients without hypertension. A Cox proportional hazard regression analysis was performed to estimate the effects of hypertension on genitourinary and gynecologic cancers risk.Among the patients with hypertension, the risks of developing renal and uterine corpus cancers were significantly higher in the hypertension group than they were in the nonhypertension group. Further stratified analyses by sex, age, and hypertension duration revealed distinct cancer-specific patterns. Higher cancer risk appears to be more obvious among younger hypertensive patients with longer follow-up time.The results of this study indicate that Taiwanese patients with hypertension have higher risks for some types of cancer, and cancer-specific patterns vary by sex, age, and hypertension duration.

Objective: To investigate the relationship between depression and risk of subsequent osteoporosis development., Participants and Methods: A population-based retrospective cohort analysis was conducted using the Longitudinal Health Insurance Database 2000 of Taiwan. We included 32,978 patients in the depression cohort and 131,912 patients in the no-depression cohort between January 1, 1998, and December 31, 2008, and calculated the incidence rates of newly diagnosed osteoporosis. We used Cox proportional hazards models to assess the effects of depression. The Kaplan-Meier method was applied to estimate the cumulative osteoporosis incidence curves., Results: Patients with depression were 1.30 times more likely to experience osteoporosis than those without depression. The risk was higher for patients with severe depression and mild depression than for those without depression. A greater hazard ratio magnitude was observed in patients aged 35 to 49 years. We also observed a significant decrease in osteoporosis risk in patients with depression treated with antidepressant agents., Conclusion: The incidence of osteoporosis in Taiwan is associated with an a priori depression history. The risk was identified in both men and women, particularly in patients aged 35 to 49 years, and was inversely correlated with antidepressant drug treatment., (Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objectives/hypothesis: The study aimed to investigate the prognostic effects of interim (18) fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (PET/CT) during definitive radiotherapy (RT) or chemoradiotherapy (CRT) in patients with head and neck cancer., Study Design: This is a prospectively treatment study., Methods: The pretreatment and interim PET/CT images of 51 patients with advanced pharyngeal cancers receiving definitive RT/CRT were evaluated prospectively. The interim PET/CT images were taken at a cumulative RT dose ranging from 41.4 to 46.8 Gy. The maximum standardized uptake value (SUVm) of the interim PET/CT and the reduction ratio of the SUVm (SRR) between the two images were measured. The differences between patients with or without local failures were examined using the Mann-Whitney test. Overall survival (OS), disease-free survival (DFS), and primary and nodal relapse-free survival rates were calculated using the Kaplan-Meier method. Independent prognosticators were identified using Cox regression analysis., Results: After a median follow-up duration of 23 months, a higher interim SUVm was associated with local failures. Conducting a multivariate analysis revealed that a SUVmax reduction ratio of primary tumor (SRR-P) < 0.64 was associated with the inferior OS (hazard ratio 2.64; P =0.035) and DFS (hazard ratio 2.33; P = 0.045). Patients who had tumors with an SRR-P < 0.64 had a considerably lower 2-year OS and DFS compared with those who had SRR-P ≥ 0.64 (47% vs. 66%; 41% vs. 64%)., Conclusion: A higher interim SUVm was associated with local recurrence. In addition, patients with a lower SRR-P should be considered to be at risk of primary failure., Level of Evidence: 4., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Aim: The present study aimed to evaluate the contribution of X-ray repair cross-complementing group 7 (XRCC7) G6721T (rs7003908) genetic polymorphism and smoking habit on the risk of lung cancer in Taiwanese., Materials and Methods: In this hospital-based case-control study, association of single nucleotide polymorphism XRCC7 G6721T with lung cancer risk were examined among 358 patients with lung cancer and 716 age- and gender-matched healthy controls. The genetic-lifestyle interaction was also investigated., Results: The results showed that the percentages of TT, GT and GG genotypes for XRCC7 G6721T were differentially distributed as 60.9%, 34.9% and 4.2% in the group of patients with lung cancer and 48.7%, 43.3% and 8.0% in the non-cancer control group, respectively (p=3.6*10(-7)). We further stratified the populations by gender and smoking behavior to investigate their combinatorial effects with XRCC7 G6721T genotype on lung cancer risk. The results showed that the GG genotype of XRCC7 G6721T had a protective effect on lung cancer susceptibility which was obvious among males and smokers (p=2.2×10(-4) and 3.1×10(-4), respectively)., Conclusion: The GG and GT genotypes of XRCC7 rs7003908 compared to the TT genotype had a protective effect on lung cancer risk in Taiwan, particularly among males and smokers., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Context: The concern regarding cancer risk has resulted in the recommendation to pull calcitonin nasal spray (CNS) from the market., Objective: We conducted a nested case-control study to evaluate the association between CNS use in osteoporosis patients in Taiwan and their subsequent risk of cancer., Design: This was a population-based nested case-control study., Setting: Data were obtained from the Taiwan National Health Insurance Research Database., Patients or Other Participants: The study cohort consisted of 28 222 patients diagnosed with osteoporosis between January 1, 2000, and December 31, 2011. We identified 1925 cancer patients as the study group and 2 noncancer patients frequency matched according to age at index date, sex, comorbidity, index-year, and osteoporosis-year as the control group., Main Outcome Measures: Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression analysis., Results: Use of CNS in women with osteoporosis significantly increased the risk of liver cancer (OR = 1.94, 95% CI = 1.23-3.05) but decreased the risk of breast cancer (OR = 0.35, 95% CI = 0.15-0.80). Further analysis of monthly CNS dosages showed that the association between CNS and liver cancer is limited to higher-dose users., Conclusion: The findings of this population-based nested case-control study suggest that CNS use might increase the risk of liver cancer in female osteoporosis patients but decrease the risk of breast cancer. Our data do not completely support the decision to discontinue use of CNS in osteoporosis patients.

Background: We conducted a population-based cohort study to assess whether tamoxifen treatment is associated with an increased incidence of diabetes., Methods: Data obtained from the Taiwanese National Health Insurance Research Database were used for a population-based cohort study. The study cohort included 22 257 breast cancer patients diagnosed between 1 January 2000 and 31 December 2004. Among them, 15 210 cases received tamoxifen treatment and 7047 did not. Four subjects without breast cancer were frequency-matched by age and index year as the control group. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariate Cox proportional hazards regression analysis., Results: Breast cancer patients exhibited a 14% higher rate of developing diabetes (adjusted HR=1.14, 95% CI=1.08-1.20) compared with non-breast cancer controls, but the significant difference was limited to tamoxifen users. In addition, tamoxifen users exhibited a significantly increased risk of diabetes compared with non-tamoxifen users among women diagnosed with breast cancer (adjusted HR=1.31, 95% CI=1.19-1.45). Stratification by age groups indicated that both younger and older women diagnosed with breast cancer exhibited a significantly higher risk of diabetes than the normal control subjects did, and tamoxifen users consistently exhibited a significantly higher diabetes risk than non-tamoxifen users or normal control subjects did, regardless of age. Both recent and remote uses of tamoxifen were associated with an increased likelihood of diabetes., Conclusions: The results of this population-based cohort study suggested that tamoxifen use in breast cancer patients might increase subsequent diabetes risk. The underlying mechanism remains unclear and further larger studies are mandatory to validate our findings.

Aim: To compare the effectiveness of intensity-modulated radiotherapy (IMRT) vs. 3D conformal radiotherapy (3DCRT) for clinical stage III non-small cell lung cancer (NSCLC) treated with primary chemoradiotherapy via a population-based retrospective cohort analysis., Patients and Methods: Using the Collaboration Center of Health Information Application (CCHIA) database, we identified 99 patients with stage III NSCLC treated with primary chemoradiotherapy from 2007 to 2009, with complete data available for analysis. We compared the risk of death within two years of diagnosis and the hazard ratio for death between those treated with IMRT and those with 3DCRT. Univariate and multivariate analyses were conducted to determine the efficacy of IMRT and 3DCRT. Sensitivity analyses were also conducted to assess relationships in the various subgroups., Results: The risk of death within two years of diagnosis was similar for IMRT and 3DCRT (36% vs. 37%, p=0.97). For the entire follow-up period, the probability of death was not statistically different when IMRT was compared to 3DCRT (p=0.8). On multivariate analysis, the adjusted hazard ratio of death was statistically insignificantly higher for IMRT vs. 3DCRT (hazard ratio of death=1.54, 95% confidence interval=0.82-2.91, p=0.18). The results remained similar in the sensitivity analyses., Conclusion: Our population-based analysis from CCHIA suggests that for patients with clinical stage III NSCLC treated with primary chemoradiotherapy, the survival outcome of those treated with IMRT was not superior to those treated with 3DCRT. Further prospective studies and cost-effectiveness analyses are warranted., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background & Aims: We investigated whether a diagnosis of colonic diverticular disease is associated with an increased risk for subsequent development of colorectal cancer (CRC) in a nationwide population-based retrospective study., Methods: We identified 41,359 individuals diagnosed with colonic diverticular disease as inpatients from 2000 through 2009 from the Taiwan National Health Insurance Research Database (study cohort) and collected data for 165,436 randomly selected additional subjects, matched by sex, age, and baseline year (comparison cohort). Data were collected until individuals developed CRC or withdrew from the National Health Insurance system, or until December 31, 2010. Cumulative incidences and hazard ratios (HRs) of CRC development were determined. To assess for ascertainment bias, we conducted an analysis excluding the first 12 months of follow-up evaluation., Results: The risk of CRC was significantly higher in the study cohort than in the comparison cohort (HR adjusted for age, sex, and comorbidities, 4.54; 95% confidence interval, 4.19-4.91; P < .0001). In a sensitivity analysis, we excluded the first 12 months of follow-up evaluation after a diagnosis of colonic diverticular disease; subsequent incidence rates for CRC in the study and comparison cohorts were 15.13 and 15.74 per 10,000 person-years, respectively (adjusted HR, 0.96; 95% confidence interval, 0.83-1.11)., Conclusions: Colonic diverticular disease is not associated with an increased risk of subsequent CRC after the first year of diagnosis of colonic diverticular disease. An increased risk was observed in the first year, possibly owing to misclassification and screening effects., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to conduct a systematic review and meta-analysis of the published literature to evaluate the diagnostic accuracy of fluorine-18 2-fluoro-2-deoxy-D-glucose (F-FDG) PET or PET/computed tomography (CT) in the pretherapeutic staging of patients with small-cell lung cancer (SCLC). The authors conducted a systematic MEDLINE search of published articles. Two reviewers independently assessed the methodological quality of each study. We estimated the pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and summary receiver operating characteristic curves in the detection of extensive disease (ED) in patients with SCLC. Twelve studies with a total of 369 patients met the inclusion criteria. The pooled estimates of sensitivity, specificity, LR+, and LR- of F-FDG PET or PET/CT for the detection of ED in SCLC were 97.5% [95% confidence interval (CI), 94.2-99.2%], 98.2% (95% CI, 94.9-99.6%), 19.86 (95% CI, 9.79-40.30), and 0.06 (95% CI, 0.03-0.10), respectively. Whole-body F-FDG PET or PET/CT is a valuable imaging tool for the pretherapeutic assessment of ED in patients with SCLC.

Objective: The objective of this study was to assess prospectively the clinical outcomes of low-dose prophylactic extended-field, intensity-modulated radiotherapy (IMRT) plus concurrent weekly cisplatin for patients with stage IB2-IIIB cervical cancer, positive pelvic lymph nodes (PLNs), and negative para-aortic lymph nodes (PALNs)., Methods: Thirty-two patients with stage IB2-IIIB cervical cancer with positive PLN and negative PALN were included prospectively. All lymph nodes were assessed with positron emission tomography. The PALN field, including lymphatics from the superior border of L1 to the L4-L5 interphase, was irradiated concurrently with pelvic IMRT with a prescribed dose of 40 Gy in 25 fractions. Chemotherapy consisted of cisplatin delivered weekly at a dose of 40 mg/m. Using historical controls treated with pelvic radiotherapy, the survival curves were compared to assess the difference between the 2 treatment periods., Results: Thirty-one patients completed the allocated extended-field IMRT, and all finished the planned pelvic IMRT and brachytherapy. Acute ≥ grade 3 gastrointestinal, genitourinary, and hematologic toxicities were seen in 2, 1, and 18 patients, respectively. During a median follow-up of 33 months, 5 patients developed out-field distant recurrences. One patient had a late grade 3 gastrointestinal complication, and 1 patient had genitourinary toxicity. The 3-year actuarial overall survival, disease-free survival, and distant metastasis-free survival for the study cohort and historic controls were 87% versus 62% (P = 0.02), 82% versus 54% (P = 0.02), and 79% versus 57% (P = 0.01), respectively., Conclusions: Extended-field IMRT of 40 Gy to the PALN plus concurrent cisplatin can effectively eradicate subclinical disease at the PALN and improve the outcome for patients with PLN-positive stage IB2-IIIB cervical cancer.

Background: Morphine is widely used for pain management in cancer patients. Use of heroin, a morphine derivative, is a risk factor for acute coronary syndrome (ACS)., Objective: This study investigates the risk of ACS associated with morphine use by comparing the incidence of ACS in cancer patients treated with and without morphine., Methods: This is a population-based nested case-control study using the Longitudinal Health Insurance Database 2000 in Taiwan. In total, 31,384 patients on the database were diagnosed with cancer without prior history of ACS during 1998-2010. In this cohort, 499 patients subsequently developed ACS and 30,885 patients did not. The 499 patients were designated as the ACS group; controls were selected from the remaining 30,885 patients and matched 3:1 to each case for age, sex, year of cancer diagnosis, and index year. Logistic regression was used to estimate the odds ratios and 95% confidence intervals, and the multivariable model was applied to control for age, sex, and Charlson comorbidity score., Results: Cancer patients who received morphine had a 32% higher risk of developing ACS than non-morphine users. This increase in risk was significant when evaluating the overall cancer patients, but non-significant when evaluating any specific cancer type. The risk of ACS increased significantly with increasing morphine dosage (to ≥65 mg/y)., Conclusion: Morphine treatment is associated with a modest increase in risk of ACS in patients with malignancy, but this association displays low significance in specific cancer types., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aim: To investigate whether hepatitis B virus (HBV) and hepatitis C virus (HCV) increase risk of pancreatic ductal adenocarcinoma (PDAC)., Methods: We recruited 585 patients with cytological and/or pathologically confirmed PDAC in National Taiwan University Hospital from September 2000 to September 2013, and 1716 age-, sex-, and race-matched controls who received a screening program in a community located in Northern Taiwan. Blood samples were tested for the presence of HCV antibodies (anti-HCV), HBV surface antigen (HBsAg), antibodies against HBsAg (anti-HBs), and hepatitis B core antigen (anti-HBc) in all cases and controls. The odds ratio (OR) of PDAC was estimated by logistic regression analysis with adjustment diabetes mellitus (DM) and smoking., Results: HBsAg was positive in 73 cases (12.5%) and 213 controls (12.4%). Anti-HCV was positive in 22 cases (3.8%) and 45 controls (2.6%). Anti-HBs was positive in 338 cases (57.8%) and 1047 controls (61.0%). The estimated ORs of PDAC in multivariate analysis were as follows: DM, 2.08 (95%CI: 1.56-2.76, P < 0.001), smoking, 1.36 (95%CI: 1.02-1.80, P = 0.035), HBsAg(+)/anti-HBc(+)/anti-HBs(-), 0.89 (95%CI: 0.89-1.68, P = 0.219), HBsAg(-)/anti-HBc(+)/anti-HBs(+), 1.03 (95%CI: 0.84-1.25, P = 0.802)., Conclusion: HBV and HCV infection are not associated with risk of PDCA after adjustment for age, sex, DM and smoking, which were independent risk factors of PDAC.

Purpose: The objective of this study was to examine the predictive role of pretreatment total lesion glycolysis (TLG) of the whole-body and primary tumors in patients with pharyngeal cancer (PC) treated with definitive radiotherapy., Methods: The retrospective analysis examined 74 PC patients treated with radiotherapy. All patients received pretreatment with F-FDG PET/CT. Several autosegmentation methods were used to determine the PET/CT-based metabolic tumor volume (MTV), TLG of the primary tumor, and whole-body TLG (TLGw) for each patient. Overall survival (OS), disease-free survival (DFS), and primary relapse-free survival (PRFS) were examined according to the cutoffs of the median values for MTV, TLG, and gross tumor volume of the primary tumor. Independent prognosticators were identified using Cox regression analysis., Results: After a median follow-up of 33 months, 42 patients remained disease-free, and 32 patients experienced cancer recurrence. Multivariate analysis of the OS and DFS showed that the application of 40% of the maximal uptake of whole body TLG(TLGw40%) was the only predictor of OS or DFS. Patients who had tumors with TLGw40% greater than 92 g had significantly lower 3-year OS and DFS compared with patients who had smaller TLGw. The independent predictors for PRFS were MTV greater than the SUVmax of 2.5 (MTV2.5)., Conclusions: For PC patients treated with definitive radiotherapy, pretreatment with TLGw40% achieved the optimal predictive value for OS and DFS, and MTV2.5 was a prognosticator for PRFS.

Background: Several studies have investigated the relationship between alopecia and prostate cancer. However, little information is available regarding the relationship between alopecia and the risk of cancers in women., Objective: The purpose of this study was to evaluate the possible association between alopecia and thyroid cancer among Taiwanese women., Methods: We used data from the National Health Insurance system of Taiwan. The alopecia cohort comprised 4534 women, and each woman was randomly frequency matched by age, index month, and index year with 4 women from the general population without alopecia. A Cox proportional hazard regression analysis with Bonferroni correction was conducted to estimate the effects of alopecia on the risk of thyroid cancer., Results: In women with alopecia, the overall risk for developing cancer was 22% higher than for subjects without alopecia, but the difference was not significant [hazard ratio (HR) = 1.22, 97.5% confidence interval (97.5% CI) = 0.87-1.70]. However, the risk for developing thyroid cancer among women with alopecia was significantly higher (HR = 2.39, 97.5% CI = 1.05-5.42). Further analyses determined that the alopecia group had a higher incidence of Graves' disease, but not Hashimoto thyroiditis., Conclusion: Although alopecia did not significantly increase cancer risks in women, we found that Taiwanese women with alopecia had a higher risk of developing thyroid cancer that is unlikely to be related to underlying thyroid diseases., (Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Purpose: This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC)., Methods and Materials: Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter., Results: Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal., Conclusions: When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: The aim of the study was to investigate the predictive role of pretreatment metabolic tumor volume (MTV) in patients with squamous cell carcinoma of locally advanced esophageal cancer treated with definitive chemoradiotherapy., Patients and Methods: Ninety patients received pretreatment with (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT, and two types of MTVs were measured on the basis of either a maximal standardized uptake value (SUVmax) of 2.5 (MTV2.5) or a fixed threshold of 20% (MTV20%). Overall survival (OS) and disease-free survival (DFS) were examined, and independent prognosticators were identified by Cox regression analysis., Results: On a median follow-up of 15 months, 51 patients were seen to have died because of tumor recurrence or other illnesses. Multivariate analysis of OS revealed that MTV20%>40 ml was the only predictor of outcome with a lower 1-year OS [P=0.003, hazard ratio (HR)=2.29, 95% confidence interval (CI) 1.36-3.91]. Two independent predictors of DFS were MTV20%>40 ml (P=0.02, HR=1.78, 95% CI 1.09-2.91) and stage IV disease (P=0.01, HR=1.84, 95% CI 1.12-3.03)., Conclusion: Pretreatment MTV20% is a novel marker for OS and DFS in patients with unresectable locally advanced esophageal cancer treated with definitive chemoradiotherapy. Treatment intensification must be considered for patients with higher MTVs.

Background and Purpose: Studies have suggested that multiple sclerosis (MS) might be linked to an overall reduced cancer rate, but a positive relationship is also found for several types of cancer. This study determines whether MS is associated with cancer risk in Taiwan., Methods: Data from the National Health Insurance System of Taiwan were used to assess this issue. The MS cohort included 1292 patients, and each patient was randomly frequency-matched with four participants without MS, based on their age, sex and index year (control cohort). Cox proportional hazards regression analysis was conducted to estimate the influence of MS on cancer risk., Results: A significantly higher risk of developing overall cancer was found amongst the MS cohort compared with the control cohort [adjusted hazard ratio (HR) 1.85, 95% confidence interval (CI) 1.26-2.74], as well as breast cancer (adjusted HR 2.23, 95% CI 1.11-4.46)., Conclusions: The nationwide population-based cohort study revealed that Taiwanese patients with MS have a higher risk of developing overall cancer types and breast cancer in particular., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)

Background: To determine the impact of body-mass factors (BMF) before radiotherapy and changes during radiotherapy on the magnitude of setup displacement in patients with head and neck cancer (HNC)., Methods: The clinical data of 30 patients with HNC was analyzed using the alignment data from daily on-line on-board imaging from image-guided radiotherapy. BMFs included body weight, body height, and the circumference and bilateral thickness of the neck. Changes in the BMFs during treatment were retrieved from cone beam computed tomography at the 10th and 20th fractions. Setup errors for each patient were assessed by systematic error (SE) and random error (RE) through the superior-inferior (SI), anterior-posterior (AP), and medial-lateral (ML) directions, and couch rotation (CR). Using the median values of the BMFs as a cutoff, the impact of the factors on the magnitude of displacement was assessed by the Mann-Whitney U test., Results: A higher body weight before radiotherapy correlated with a greater AP-SE (p = 0.045), SI-RE (p = 0.023), and CR-SE (p = 0.033). A longer body height was associated with a greater SI-RE (p = 0.002). A performance status score of 1 or 2 was related to a greater AP-SE (p = 0.043), AP-RE (p = 0.015), and SI-RE (p = 0.043). Among the ratios of the BMFs during radiotherapy, the values at the level of mastoid tip at the 20th fraction were associated with greater setup errors., Conclusions: To reduce setup errors in patients with HNC receiving RT, the use of on-line image-guided radiotherapy is recommended for patients with a large body weight or height, and a performance status score of 1-2. In addition, adaptive planning should be considered for those who have a large reduction ratio in the circumference (<1) and thickness (<0.94) over the level of the mastoid tip during the 20th fraction of treatment.

Background: This study investigated the relationship between recent morphine use and risk of subdural haemorrhage (SDH) in patients with cancer., Methods: This study identified a malignancy cohort of 25,322 patients who had never received morphine treatment. In this malignancy cohort, 200 patients who subsequently developed SDH were designated as the SDH group. Control-group patients without SDH were selected from the malignancy cohort and were matched ∼4:1 to each SDH case for age, sex, year of cancer diagnosis and index year. Morphine use was designated as 'recent' if the prescription duration covered the index date or ended within 6 months before the index date. Logistic regression was used to estimate odds ratios and 95% confidence intervals and a multivariable model was applied to control for age, sex and cerebrovascular disease., Results: Compared with non-morphine users, patients with cancer who received morphine within 6 months of the index date exhibited a 2.58-fold (95% CI = 1.23-5.39) increase in the risk of developing SDH. The risk of SDH development increased as the duration of morphine treatment increased., Conclusion: The incidence of SDH in patients with cancer in Taiwan is associated with recent morphine treatment (≤6 months) and is dependent on the duration of morphine use.

Objective: To evaluate the risk of prostate and bladder cancers in patients with spinal cord injury (SCI)., Materials and Methods: We used data obtained from the National Health Insurance system of Taiwan for this study. The SCI cohort contained 54,401 patients with SCI, and each patient was randomly frequency matched with 4 people from the general population (without SCI) based on age, sex, and index date. Incidence rates, SCI cohort to non-SCI cohort rate ratios, and hazard ratios were measured to evaluate the cancer risks., Results: Patients with SCI showed a significantly lower risk of developing prostate cancer compared with subjects without SCI (adjusted hazard ratio = 0.73; 95% confidence interval = 0.59, 0.90), after accounting for the competing risk of death. No significant difference in the risk of bladder cancer emerged between the SCI and control groups. Further analyses found a higher spinal level of SCI tended to predict a lower risk for prostate cancer., Conclusions: Patients with SCI incurred a lower risk for prostate cancer compared with people without SCI. The risk for bladder cancer did not differ between people with or without SCI., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This paper presents a population-based retrospective cohort study to identify the differences in secondary primary cancer (SPC) among hypopharyngeal, laryngeal, and other sites of head and neck cancer (HNC). Data were collected from the Taiwan National Health Insurance Research Database (NHIRD) for the period 1979-2010. The study cohort comprised 5914 newly diagnosed hypopharyngeal and laryngeal patients from the registry of the Catastrophic Illness Patients Database (CIPD). The comparison cohort comprised 5914 patients with other sites of HNC. We used a multivariate Cox proportional-hazards regression model to assess the risk of developing SPC. The incidence of SPC in the study cohort was 68% higher compared with the comparison cohort (23.9 vs. 14.2 per 1000 person-years, Incident Rate Ratio = 1.68). The study cohort had a higher adjusted hazard ratio (HR) in oesophageal cancer (HR = 3.47) and lung cancer (HR = 1.89). The difference in SPC incidence between the study and comparison cohort was significant., (© 2013 John Wiley & Sons Ltd.)

Objectives: Few studies have investigated the relationship between ankylosing spondylitis (AS) and other inflammatory spondyloarthritis and subsequent cancer. The aim of this study was to determine whether AS is associated with cancer risk., Method: We used data from the National Health Insurance (NHI) system of Taiwan to investigate this association. The AS cohort included 4133 patients, and each patient was randomly frequency matched with four persons without AS based on sex, age, and entry year (control cohort). We conducted a Cox proportional hazards regression analysis to estimate the influence of AS on cancer risk., Results: Among patients with AS, the overall risk of developing cancer was 38% higher than that of people without AS, and the difference was significant [adjusted hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.18-1.60]. This phenomenon held true even when we analysed males and females separately. The risk of developing lung or head and neck cancer among patients with AS was significantly higher; and risks for liver, bladder, and uterus cancers were marginally significantly higher., Conclusions: This nationwide population-based cohort study shows that Taiwanese patients with AS have a higher risk of developing cancer, particularly lung or head and neck cancer.

Rationale and Objectives: Although low-dose computed tomography (CT) is a recommended modality for lung cancer screening in high-risk populations, the role of other modalities, such as [(18)F]fluorodeoxyglucose-positron emission tomography (PET), is unclear. We conducted a systematic review to describe the role of PET in lung cancer screening., Materials and Methods: A systematic review was conducted by reviewing primary studies focusing on PET screening for lung cancer until July 2012. Two independent reviewers identified studies that were compatible for inclusion/exclusion criteria. The analysis was restricted to English and included studies published since 2000. A descriptive analysis was used to summarize the results, and the pooled diagnostic performance of selective PET screening was calculated by weighted average using individual sample sizes., Results: Among the identified studies (n = 3497), 12 studies were included for analysis. None of the studies evaluated the efficacy of primary PET screening specific to lung cancer. Eight studies focused on primary PET screening for all types of cancer; the detection rates of lung cancer were low. Four studies reported evidence of lung cancer screening programs with selective PET, in which the estimated pooled sensitivity and specificity was 83% and 91%, respectively., Conclusions: The role of primary PET screening for lung cancer remains unknown. However, PET has high sensitivity and specificity as a selective screening modality. Further studies must be conducted to evaluate the use of PET or PET/computed tomography screening for high-risk populations, preferably using randomized trials or prospective registration., Advances in Knowledge: Our meta-analysis indicates that PET has high sensitivity and specificity as a selective screening modality.

Objective: To evaluate the association between urinary tract stone (UTS) and urinary tract cancer (UTC) in Taiwanese patients, as the results of epidemiological studies about the relationship between UTS and the development of UTC remain inconclusive., Patients/subjects and Methods: We conducted a population-based cohort study using data from the Taiwanese National Health Insurance system. The UTS cohort included 21 862 patients, and each patient was randomly frequency-matched for age, sex, and index year with two insured members of the general population who did not have UTS. Cox proportional hazard regression analysis was performed to estimate the effect of UTS on the risk of UTC., Results: Patients with UTS were at a significantly higher risk of developing UTC compared with the comparison group (adjusted hazard ratio 4.66; 95% confidence interval 2.97-7.30). Women were at higher risk than men. Further analyses showed that the level of UTC was associated with that of UTS, and that the risk for UTC became more divergent for the two groups over time., Conclusions: Taiwanese patients with UTS, particularly women, had a higher risk for developing UTC than patients without UTS. The risk became more marked over time for this group., (© 2013 The Authors. BJU International © 2013 BJU International.)

Purpose: We conducted a nested case-control study to evaluate the association between risk of cancer and mirtazapine use in depression patients in Taiwan., Methods: We obtained data from the Taiwan National Health Insurance Research Database to conduct a population-based nested case-control study. The study cohort included 16 897 patients diagnosed with depression between January 1, 2000 and December 31, 2008. We identified 530 cancer patients as the study group and matched 4 non-cancer subjects with each cancer patient by incident density, age, and sex. Odds ratios and 95% confidence intervals were estimated using multivariate conditional logistic regression analysis., Results: Use of mirtazapine for depression did not have significant effect on overall cancer incidence (odds ratio: 1.03, 95% confidence interval: 0.72-1.48). Further analysis of annual mirtazapine dosages and the duration of mirtazapine use revealed no significant effect on cancer risk., Conclusion: The findings of this population-based nested case-control study suggest that mirtazapine use may not provide a tumor suppression effect in humans such as that seen in the animal model. Future large-scale and in-depth investigations in this area are warranted., (Copyright © 2013 John Wiley & Sons, Ltd.)

This study compared TomoTherapy (TM), with Volumetric-Modulated Arc Therapy (RapidArc, RA), and dynamic intensity-modulated radiotherapy (dIMRT) for locally advanced esophageal cancer (LAEC) with a simultaneous integrated boost (SIB) technique with regard to the target coverage and sparing of organs at risk (OARs). Twelve patients receiving four-dimensional computed tomography simulation were enrolled for dosimetric comparison. Gross tumor volume was contoured with the maximum intensity projection method. Using an SIB method, Planning target volume low (PTVL) and planning target volume high (PTVH) were prescribed as 54 Gy and 60 Gy, respectively, each administered in 30 fractions. We compared the results of statistical analysis for target coverage, homogeneity index (HI) and conformity index (CI) of PTVs, parameters of OARs and monitor unit (MU) were compared for analysis. The HI for PTVH varied significantly for the 3 techniques of TM, RA, and dIMRT (4.38 ± 0.86, 6.40 ± 0.86, and 6.11 ± 0.68, respectively; P , 0.001). The CI scores for PTVH also differed across TM, RA, and dIMRT (0.64 6 0.06, 0.53 6 0.06, and 0.59 ± 0.05, respectively; P < 0.001). The HI for PTVL showed a significant difference among TM, RA, and dIMRT (15.44 ± 0.88, 20.88 ± 1.03 and 18.65 ± 1.42, respectively; P < 0.001). The percentage of lung volume receiving 5 Gy (V5) and 20 Gy (V20) (for V5: TM 54.4 ± 8.0%; RA 67.5 ± 14.5%, P < 0.01; dIMRT 44.8 ± 8.2%; for V20: 13.6 6 3.3%, 12.2 ± 3.6%, 18.1 6 3.4%, P = 0.001, respectively). For RA, the lung V5 ≥ 65% was observed in 6 patients and the V10 ≥ 50 % in one patient. TM, RA and dIMRT provided comparable coverage of the target and sparing of OARs. TM demonstrated superior CI and HI for tumor coverage and lowered the specified dose parameters for lung. RA provided an advantage in terms of the lowest MU and V20 of the lung, but its higher lung V5 was of some concern about lung toxicity.

Background and Objectives: Patients with node-negative breast cancer (NNBC) usually have a good prognosis, but tumor recurrence still compromises survival. In this study, we sought to identify clinical and pathologic factors that predict recurrence., Methods: A total of 716 patients who were proved with pT1-2N0M0 breast cancer between 2005 and 2009 were enrolled in this study., Results: Forty-seven of the 716 patients developed tumor recurrence during the 47.0 months of median follow-up. The significant risk factors of recurrence were lymphovascular invasion (LVI) (hazard ratio [HR] = 4.60, 95% CI. 2.32-9.10) and Nottingham grade 3 (HR = 4.99, 95% CI. 1.06-23.48); adjuvant radiotherapy (HR = 0.35, 95% CI. 0.14-0.92) prevented tumor recurrence. Furthermore, we investigate the therapeutic impact of adjuvant chemotherapy and radiotherapy on patients with LVI and Nottingham grade 3. The adverse effect of LVI and grade 3 can be abrogated by adjuvant radiotherapy in recurrence-free survival (RFS) (LVI((+)) radiotherapy((+)) , no recurrence; grade 3((+)) radiotherapy((+)) , HR = 0.82, 95% CI. 0.18-3.70). However, adjuvant chemotherapy did not., Conclusions: LVI and Nottingham grade 3 were the independent risk factors predicting tumor recurrence for patients with NNBC. Adjuvant radiotherapy might be considered in NNBC patients with these unfavorable factors to improve the RFS., (© 2013 Wiley Periodicals, Inc.)

Unlabelled: Chronic use of morphine is a risk factor for endocrinopathy and osteoporosis. Bisphosphonates accentuated the protective effect to develop osteoporosis in female patients with malignancy with morphine treatment., Introduction: This study investigates the risk of osteoporosis associated with morphine use by comparing the incidence of osteoporosis in female cancer patients treated with and without morphine., Methods: A population-based nested case-control retrospective analysis was performed using the Longitudinal Health Insurance Database 2000 and Registry for Catastrophic Illness Patients of Taiwan. A malignancy cohort of 12,467 female patients without a history of osteoporosis during 1998-2010, and then 639 patients who subsequently developed osteoporosis as the osteoporosis group, were evaluated. Control-group patients were selected from the malignancy cohort without osteoporosis and frequency matched to each osteoporosis case 2:1 for age, year of cancer diagnosis, and index year. Logistic regression was used to estimate the odds ratios and 95% confidence intervals, and the multivariable model was applied to control for age., Results: Female cancer patients who received morphine had a 10% lower risk of developing osteoporosis than non-morphine users, but this risk reduction was not significant. For patients treated with bisphosphonates, the morphine group had significantly lower odds in developing osteoporosis than the non-morphine group., Conclusion: Morphine treatment is not associated with the incidence of osteoporosis, and bisphosphonates accentuated the protective effect of morphine in the development of osteoporosis in female patients with malignancy in Taiwan.

Objective: To provide an efficient way for tracking patients' condition over long periods of time and to facilitate the collection of clinical data from different types of narrative reports, it is critical to develop an efficient method for smoothly analyzing the clinical data accumulated in narrative reports., Materials and Methods: To facilitate liver cancer clinical research, a method was developed for extracting clinical factors from various types of narrative clinical reports, including ultrasound reports, radiology reports, pathology reports, operation notes, admission notes, and discharge summaries. An information extraction (IE) module was developed for tracking disease progression in liver cancer patients over time, and a rule-based classifier was developed for answering whether patients met the clinical research eligibility criteria. The classifier provided the answers and direct/indirect evidence (evidence sentences) for the clinical questions. To evaluate the implemented IE module and the classifier, the gold-standard annotations and answers were developed manually, and the results of the implemented system were compared with the gold standard., Results: The IE model achieved an F-score from 92.40% to 99.59%, and the classifier achieved accuracy from 96.15% to 100%., Conclusions: The application was successfully applied to the various types of narrative clinical reports. It might be applied to the key extraction for other types of cancer patients.

Unlabelled: The present study assessed the diagnostic performances of (18)F-FDG PET or PET/CT in detecting peritoneal carcinomatosis in patients with cancer., Methods: Through a search of MEDLINE (January 1998 to September 2012), an overall weighted average for sensitivity and specificity was calculated using the weighted averages of the sample sizes in each relevant study. Pooled estimates of positive and negative likelihood ratios were calculated using fixed and random effects models, respectively, according to the heterogeneity among studies. A summary receiver operating characteristics (sROC) curve was constructed and the area under the sROC curve (AUC) was calculated. To explore heterogeneity, due to sources other than threshold effects, I-square was calculated., Results: The present study included analyses of patients (n = 513) from 7 studies. Results indicated a significant heterogeneity for sensitivity and specificity (I(2) > 50% and P < 0.05). The overall pooled estimates for sensitivity and specificity of FDG PET or PET/CT scans in the detection of peritoneal carcinomatosis were 72.4% (95% CI, 64.4%-79.5%) and 96.7% (95% CI, 94.4%-98.3%), respectively. The positive likelihood ratio was 10.414 (95% CI, 6.195-17.506) and the negative likelihood ratio 0.312 (95% CI, 0.159-0.612). The AUC was 0.9404. The overall diagnostic accuracy (Q* index) was 87.8%., Conclusion: The high specificity may provide the reliability of a positive FDG PET or PET/CT to detect peritoneal carcinomatosis in patients with cancer. FDG PET or PET/CT has only weak power to exclude the presence of peritoneal carcinomatosis. By a good overall diagnostic accuracy, FDG PET or PET/CT may prove beneficial to surgeons when selecting appropriate patients on whom to perform laparoscopy or laparotomy.

Objectives: We address the potential problem of stroke induced by morphine exposure by comparing the incidence of stroke in cancer patients treated with and without morphine., Methods: We performed a population-based nested case–control retrospective analysis on the Longitudinal Health Insurance Database 2000 and Registry for Catastrophic Illness Patients of Taiwan. This study is based on a malignancy cohort of 31 611 patients without a history of stroke, and 1208 patients who subsequently developed stroke served as the stroke group. Four controls of matched age, sex, entry year and entry month for each case were selected from the malignancy cohort from the non-stroke group. We used logistic regression to estimate the odds ratios and 95% confidence intervals, and applied the multivariable model to control for age, sex, hypertension, diabetes, hyperlipidemia and cardiovascular disease., Results: Cancer patients who received morphine had a 12% higher risk of developing stroke than non-morphine users. However, the difference was nonsignificant. A significant difference only appears in prostate cancer patients, where morphine users have a 3.02-fold (4.24- and 2.90-fold for hemorrhagic and ischemic strokes, respectively) higher risk of suffering from stroke. The risk increased significantly as the morphine dosage increased to 170 mg/year of treatment., Conclusions: Intense morphine treatment may be associated with an increased stroke incidence in patients with malignancy, and the association is particularly significant for prostate cancer patients.

Primary infiltrating ductal carcinoma of the axillary breast is rare and has a high frequency of lymph node (LN) involvement. We report a woman with primary infiltrating ductal carcinoma arising from the right axillary breast with metastasis to the contralateral chest wall. Excisional biopsy of the left chest wall nodule and the right axillary mass was carried out and both showed invasive ductal carcinomas histologically. The lesion of the right axillary mass arose from the breast tissue, rather than the LN. Further surgery proved the right axillary LN metastasis. After further review, a primary infiltrating ductal carcinoma of the right axillary breast with metastasis to axillary LNs and contralateral chest wall was diagnosed. The patient also received chemotherapy and radiation and there was no evidence of tumor recurrence after treatment. The present report demonstrated a rare case with uncommon manifestation. Lesions of uncertain origin around the periphery of the breast should be suspected for breast carcinoma., (Copyright © 2013. Published by Elsevier B.V.)

Background: Comparing initial 45 Gy of pelvic intensity-modulated radiation therapy (IMRT) and non-IMRT in terms of the late toxicities associated with advanced cervical cancer that has also been treated with definitive concurrent chemoradiotherapy and high-dose rate intracavitary brachytherapy (HDRICB)., Patients and Methods: This retrospective study included 320 stage IB2-IIIB cervical cancer patients treated with CCRT (83 IMRT and 237 non-IMRT). The two groups had similar stage and HDRICB ratings. Following 45 Gy to the pelvis, HDRICB of 24 Gy in four courses was prescribed. Late toxicities, including rectal complications (RC), bladder complications (BC) and non-rectal intestinal injury (NRRII), were scored by the Common Terminology Criteria for Adverse Events. A logistic regression was used to estimate the odds ratio (OR) of the complications., Results: With a median follow-up duration of 33 and 77 months for IMRT and non-IMRT, 33 patients had Grade 2 or higher late RC (7.2% IMRT, 11.4% non-IMRT), whereas that for BC was 40 (9.6% IMRT, 13.5% non-IMRT) and for NRRII was 48 (12.0% IMRT, 16.0% non-IMRT). The cumulative rate for total grade 3 or higher gastrointestinal or genitourinary toxicities was 8.4% and 11.8% (p = 0.33). IMRT did not reduce the OR for all endpoints; however, the ORs for rectum and bladder reference doses to Point A were associated with RC and BC., Conclusions: Locally advanced cervical cancer patients treated with initial 45Gy of pelvic IMRT and HDRICB have similar treatment-related late toxicities as those treated with non-IMRT. Optimization of the brachytherapy scheme is essential to minimize late toxicities.

This study examines the possible association between urinary tract infection (UTI) and urinary tract cancer (UTC). Data from the National Health Insurance system of Taiwan were used for the analysis. The UTI cohort included 70 116 patients who were diagnosed and recruited between 1997 and 2010. Each patient was randomly frequency-matched with two people without UTI from the general population based on their age, sex, and month of UTI diagnosis. Cox's proportional hazard regression analysis was used to estimate the effects of UTI on UTC risk until the end of follow-up on December 31, 2010. Patients with UTI had a significantly higher risk of developing UTC than healthy people (adjusted hazard ratio, 4.66; 95% confidence interval, 3.55-6.10). Further analyses indicated that risks are potentially related to the level of the lesion site. This study indicated that patients with UTI had a higher risk of developing UTC., (© 2013 Japanese Cancer Association.)

Background: To evaluate whether the location of moist desquamation matches high dose area for breast cancer patients receiving adjuvant radiotherapy (RT) after breast conservative surgery., Methods: One hundred and nine breast cancer patients were enrolled to this study. Their highest skin dose area (the hot spot) was estimated from the treatment planning. We divided the irradiated field into breast; sternal/parasternal; axillary; and inframammary fold areas. The location for moist desquamation was recorded to see if it matches the hot spot. We also analyzed other possible risk factors which may be related to the moist desquamation., Results: Forty-eight patients with 65 locations developed moist desquamation during the RT course. Patients with larger breast sizes and easy to sweat are two independent risk factors for moist desquamation. The distribution of moist desquamation occurred most in the axillary area. All nine patients with the hot spots located at the axillary area developed moist desquamation at the axillary area, and six out of seven patients with the hot spots located at the inframammary fold developed moist desquamation there. The majority of patients with moist desquamation over the breast or sternal/parasternal areas had the hot spots located at these areas., Conclusions: For a patient with moist desquamation, if a hot spot is located at the axillary or inframammary fold areas, it is very likely to have moist desquamation occur there. On the other hand, if moist desquamation occurs over the breast or sternal/parasternal areas, we can highly expect these two areas are also the hot spot locations.

Background: A meta-analysis was conducted to evaluate the accuracy of whole-body positron emission tomography (PET) or PET/CT in M staging of nasopharyngeal carcinoma (NPC)., Methods: Through a search of relevant English language studies from October 1996 to September 2011, pooled estimated sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and summary receiver operating characteristic (SROC) curves of whole-body PET or PET/CT in M staging of NPC were calculated., Results: Three PET and 5 PET/CT studies were identified. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of FDG-PET or PET/CT were 0.83 (95% confidence interval [CI], 0.77-0.88), 0.97 (95% CI, 0.95-0.98), 23.38 (95% CI, 16.22-33.69), and 0.19 (95% CI, 0.13-0.25), respectively. The area under curve was 0.9764 and Q* index estimate was 0.9307 for FDG-PET or PET/CT., Conclusion: Current evidence confirms the good diagnostic performance of the whole-body FDG-PET or PET/CT in M staging of NPC., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: The purpose of the study was to explore the possible association between the use of insulin sensitizers (thiazolidinediones, TZDs) and the risk of cancer in Taiwanese diabetic patients., Patients and Methods: From the National Health Insurance Research Database (NHIRD) of Taiwan, we identified 22 910 diabetic patients newly diagnosed from 2001 to 2009 and 91 636 non-diabetic comparisons frequency matched with age, sex, and calendar year, excluding those with cancer at the baseline. Among the diabetics, 4159 patients were treated with TZDs and the rest of 18 752 patients were on other anti-diabetic medications (non-TZDs)., Results: In comparison to the non-diabetes group, the non-TZDs group had an increased risk of developing cancer [the adjusted hazard ratio (HR): 1.20 and 95% confidence interval (CI) = 1.11-1.30]. The TZDs group had a HR of 1.18 (95% CI = 0.98-1.42). Analysis of site-specific cancer risks showed that both TZDs and non-TZDs groups with elevated risks of colorectal and pancreatic cancer. However, the non-TZDs group had an increased risk of liver cancer when comparing with TZD and non-diabetes groups., Conclusion: This study suggests that patients with diabetes are at an elevated risk of cancer (especially in colorectal and pancreatic cancers), and the use of TZDs might decrease the liver cancer risk in diabetic patients. Further investigation using large samples and rigorous methodology is warranted.

Background and Purpose: Currently, the inhomogeneity of the pulmonary function is not considered when treatment plans are generated in thoracic cancer radiotherapy. This study evaluates the dose of treatment plans on highly-functional volumes and performs functional treatment planning by incorporation of ventilation data from 4D-CT., Materials and Methods: Eleven patients were included in this retrospective study. Ventilation was calculated using 4D-CT. Two treatment plans were generated for each case, the first one without the incorporation of the ventilation and the second with it. The dose of the first plans was overlapped with the ventilation and analyzed. Highly-functional regions were avoided in the second treatment plans., Results: For small targets in the first plans (PTV < 400 cc, 6 cases), all V5, V20 and the mean lung dose values for the highly-functional regions were lower than that of the total lung. For large targets, two out of five cases had higher V5 and V20 values for the highly-functional regions. All the second plans were within constraints., Conclusion: Radiation treatments affect functional lung more seriously in large tumor cases. With compromise of dose to other critical organs, functional treatment planning to reduce dose in highly-functional lung volumes can be achieved.

Cancer cells respond to stress by activating a variety of survival signaling pathways. A disintegrin and metalloproteinase (ADAM) 9 is upregulated during cancer progression and hormone therapy, functioning in part through an increase in reactive oxygen species. Here, we present in vitro and in vivo evidence that therapeutic targeting of ADAM9 gene expression by lentivirus-delivered small hairpin RNA (shRNA) significantly inhibited proliferation of human prostate cancer cell lines and blocked tumor growth in a murine model of prostate cancer bone metastasis. Cell cycle studies confirmed an increase in the G1-phase and decrease in the S-phase population of cancer cells under starvation stress conditions, which correlated with elevated intracellular superoxide levels. Microarray data showed significantly decreased levels of regenerating islet-derived family member 4 (REG4) expression in prostate cancer cells with knockdown of ADAM9 gene expression. This REG4 downregulation also resulted in induction of expression of p21(Cip1/WAF1), which negatively regulates cyclin D1 and blocks the G1/S transition. Our data reveal a novel molecular mechanism of ADAM9 in the regulation of prostate cancer cell proliferation, and suggests a combined modality of ADAM9 shRNA gene therapy and cytotoxic agents for hormone refractory and bone metastatic prostate cancer.

Unlabelled: The present study assessed the diagnostic performances of 18F-FDG PET or PET/CT in detecting pelvic and/or paraaortic lymph node metastasis in patients with endometrial cancer., Methods: Through a search of MEDLINE (January 1998 to March 2011), an overall weighted average for sensitivity and specificity as well as pooled estimates of positive and negative likelihood ratios were calculated. A summary receiver-operating-characteristics (sROC) curve was constructed and the area under the sROC curve (AUC) was calculated. I-square was calculated to explore heterogeneity., Results: The present study included 243 patients from seven studies. Results indicated a lack of significant heterogeneity for sensitivity and specificity (I2<50% and p>0.05). The overall pooled estimates for sensitivity and specificity of FDG-PET or PET/CT scans in the detection of pelvic and/or paraaortic metastasis were 63.0% (95% CI, 48.7-75.7%) and 94.7% (95% CI, 90.4-97.4%), respectively. The positive likelihood ratio was 10.465 (95% CI, 5.646-19.396) and the negative likelihood ratio 0.399 (95% CI, 0.284-0.560). The AUC was 0.9533. The overall diagnostic accuracy (Q* index) was 89.5%. Conclusion The high positive likelihood value confirms the reliability of a positive FDG-PET or PET/CT to detect pelvic and/or paraaortic lymph nodes metastasis in patients with untreated endometrial cancer. FDG-PET or PET/CT may prove beneficial to surgeons when selecting appropriate patients on whom to perform lymphadenectomy., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Unlabelled: Lymph node staging in non-small cell lung cancer (NSCLC) is challenging and important for deciding treatment policy. The role of PET/CT scans in lymph node staging of NSCLC remains controversial when comparing TB and non-TB endemic regions. This study systematically reviews the literature regarding the diagnostic performance of PET/CT in lymph node staging of patients with NSCLC, and determines its pooled sensitivity and specificity., Methods: The databases of PubMed, Medline, and Cochrane library were searched for relevant studies. Two reviewers independently assessed the methodological quality of each study. A meta-analysis of the reported sensitivity and specificity of each study was performed., Results: Seven of 86 studies were included. These studies had moderate to good methodological quality. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for patient-based analyses (five studies) were 66%, 92.7%, 5.86%, and 0.41%, respectively, and those for lesion-based analyses (six studies) were 59.4%, 96.5%, 9.37%, and 0.31%, respectively. Subanalysis of endemic regions of tuberculosis (TB) showed that these regions had lower sensitivity and similar specificity to non-TB endemic regions., Conclusion: PET/CT showed high specificity in the lymph node staging of NSCLC and lower sensitivity in TB endemic regions., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: Neuroendocrine cervical carcinoma is a rare subtype of cervical cancer. These tumors exhibit an aggressive behavior with early regional lymph node and distant metastases. The purpose of our study was to describe five cases of neuroendocrine cervical-vaginal carcinoma and to discuss the potential of the 2-[(18)F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) scan for the detection of this rare malignancy., Materials and Methods: Five cases of cervical-vaginal neuroendocrine tumor were retrospectively collected, during a two year (from September 2009 to August 2011) period in our hospital. The clinical staging distributions were International Federation of Gynecology and Obstetrics (FIGO) stage IB2 (1 of 5), stage IIA (3 of 5) and stage IVA (1 of 5)., Results: Two cases (cases 1 and 4) were restaged after (18)F-FDG PET/CT scan in the initial staging process. Post-treatment (18)F-FDG PET/CT scans, in three patients, revealed positive findings for tumor recurrence or lymph node metastases. Two patients (cases 2 and 3) died of tumor within two years., Conclusion: (18)F-FDG PET/CT scan is a useful tool in cervical-vaginal neuroendocrine tumor. In its initial staging, the (18)F-FDG PET/CT scan may help assess the possible nodal involvement or early hematogeneous spreading. We can also use the (18)F-FDG PET/CT to detect local recurrence and to evaluate the treatment response after clinical manipulation.

Background: The purpose of this study was to explore the possible association between coronary artery disease (CAD) risk and cervical cancer., Methods: We used data from the National Health Insurance system of Taiwan to address the research topic. The exposure cohort contained 728 patients with cervical cancer. Each cancer patient was randomly frequency-matched with 4 participants by age, index-month, and index-year from the general population who did not have a cancer history before the index date (control group). Cox's proportion hazard regression analyses were conducted to estimate the relationship between cervical cancer and CAD risk., Results: Among patients with cervical cancer, the overall risk for developing CADs was significantly lower than that of the control group [adjusted hazard ratio (aHR): 0.57, 95% confidence interval (95% CI): 0.41-0.79]. Further analyses revealed that the lower risk was observed only in patients with older age (aHR: 0.57, 95% CI: 0.40-0.82), a shorter follow-up duration (aHR: 0.47, 95% CI: 0.31-0.72), or with estrogen supplements (aHR: 0.39, 95% CI: 0.22-0.68)., Conclusions: The findings from this population-based study suggest that estrogen supplements are associated with a decreased CAD risk in patients with cervical cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We performed a meta-analysis to assess the potential value of dual-time-point (DTP) imaging as compared with initial single-time-point (STP) scanning with 18F-fluorodeoxyglucose (18F-FDG) PET in differentiating malignant from benign single pulmonary nodules. Data on the performance of DTP 18F-FDG PET imaging in assessing lung nodules were extracted from articles of prospective or retrospective original research published between January 2001 and April 2010. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used to assess the quality of study methodology. Heterogeneity in the results of the studies was assessed, and summary receiver operating characteristic (SROC) curves were constructed. Eleven studies comprising a total of 788 patients who underwent initial scanning, 778 of whom also underwent DTP imaging, were included in the final analysis. The quality of study methodology was judged to be moderate. Substantial heterogeneity in the results of the studies, with inconsistency (I2) index values above 85%, reflected important differences in study methods and populations, including varying lesion sizes, 18F-FDG avidity, uptake interval for delayed imaging, and threshold for positive result on DTP imaging. SROC curve analysis revealed a statistically nonsignificant trend toward higher sensitivity with DTP imaging, at moderate levels of specificity, when compared with initial STP scanning. The area under the curve (SE) values for DTP and initial STP imaging were 0.839 (0.079) and 0.757 (0.074), respectively. Although the results of our analysis do not support the routine use of DTP imaging with 18F-FDG PET in the differential diagnosis of pulmonary nodules, this technique may provide additional information in selected cases with equivocal results from initial scanning. Further prospective research is required to better define the potential benefits of DTP 18F-FDG PET imaging.

Objectives: To explore the possible association between the risk of coronary artery disease and head or neck cancer based on some possible shared risk factors and/or treatment-related complications., Design and Setting: A population-based retrospective cohort study., Participants: All new 729 patients with head and neck cancer diagnosed between 2000 and 2003 were followed up till 2009, and the risk of subsequent coronary artery disease was calculated. For each patient, the risk was calculated in 4 age-and sex-matched population controls. Matching was not possible for factors including socio-economic group and smoking., Main Outcome Measures: Cox's proportional hazard regression analysis was conducted to estimate the relationship between head or neck cancer and risk of coronary artery disease., Results: For patients with head or neck cancer, the overall risk for developing coronary artery disease was almost the same as that of the control group [adjusted hazard ratio (but without control for some lifestyle factors): 0.95; 95% confidence interval: 0.65-1.35]. Overall, we found no increased risk of coronary artery disease for patients with head or neck cancer when the data were categorised either by treatment methods or by cancer subsites., Conclusions: This population-based study indicated that patients with head or neck cancer were at no higher risk of developing coronary artery disease than was the general population over a 6- to 9-year period; however, we cannot exclude the risk over a longer period of time., (© 2012 Blackwell Publishing Ltd.)

Aim: The purpose of the current study was to conduct a systematic review and meta-analysis of the published literature to evaluate the diagnostic accuracy of FDG PET or PET/CT for intramedullary and extramedullary lesions in multiple myeloma., Methods: The authors conducted a systematic MEDLINE search of published articles. Two reviewers independently assessed the methodological quality of each study. We estimated pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and summary receiver operating characteristic curves in the detection of intramedullary and extramedullary lesions in multiple myeloma., Results: Fourteen studies with a total of 395 patients met the inclusion criteria. The pooled estimates of sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of FDG PET or PET/CT for the detection of extramedullary lesions in multiple myeloma were 96.0% [95% confidence interval (CI), 79.6%-99.9%], 77.8% (95% CI, 40.0%-97.2%), 3.28 (95% CI, 1.29-8.32), and 0.12 (95% CI, 0.03-0.42), respectively. The pooled estimates of sensitivity, specificity, LR+, and LR- of FDG PET or PET/CT for the detection of intramedullary lesions in multiple myeloma were 61.1% (95% CI, 43.5%-76.9%), 94.1% (95% CI, 71.3%-99.9%), 5.73 (95% CI, 1.53-21.40), and 0.43 (95% CI, 0.28-0.65), respectively., Conclusions: Whole-body FDG PET or PET/CT is a valuable imaging tool for the assessment of patients with multiple myeloma, especially for the appraisal of extramedullary involvement.

Aim: Positron emission tomography (PET) using F18-flurodeoxy-glucose (FDG) has been widely used for reflecting cellular metabolism. However, the feasibility of FDG PET in the diagnosis of hepatocellular carcinoma (HCC) is limited. The aim of the study was to assess the ability of FDG PET (PET/CT) in the detection of extrahepatic metastases or recurrent HCC., Materials and Methods: We conducted MEDLINE, EMBASE and COCHRANE searches (last update, April 2011). Eight eligible articles were identified evaluating F18-FDG PET (PET/CT) in extrahepatic metastases or recurrent HCC. Two authors independently evaluated the methodological quality of each study. We estimated pooled sensitivities, specificities, summary receiver-operating-characteristic (SROC) curves, and summary likelihood ratios., Results: Eight eligible studies were enrolled in this study. The pooled estimates of sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of FDG PET (PET/CT) in the detection of metastatic HCC were 76.6%, 98.0%, 14.68, and 0.28, respectively. The pooled estimates of sensitivity, specificity, LR+ and LR- of FDG PET (PET/CT) in the detection of recurrent HCC were 81.7%, 88.9%, 4.72, and 0.19, respectively., Conclusion: Based on the results of this systematic review, F-18 FDG PET (PET/CT) was useful in ruling in extrahepatic metastases of HCC and valuable for ruling out the recurrent HCC., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)