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Statins and Metformin Use Is Associated with Lower PSA Levels in Prostate Cancer Patients Presenting for Radiation Therapy
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作者 Xiaonan Liu Jing Li +5 位作者 Steven E. Schild Michael H. Schild William Wong Sujay Vora Michael G. Herman mirek fatyga 《Journal of Cancer Therapy》 2017年第2期73-85,共13页
Background: A possible association between the level of prostate specific antigen (PSA) and the use of some commonly prescribed medications has been reported in recent studies. Most of these studies were carried out i... Background: A possible association between the level of prostate specific antigen (PSA) and the use of some commonly prescribed medications has been reported in recent studies. Most of these studies were carried out in general populations of men who were screened for prostate cancer using the PSA test. We reported on the association between the initial PSA level and the use of statins, metformin and alpha-blockers in patients who were diagnosed with prostate cancer and presented for radiation therapy. Methods: Three hundred and eighty one patients treated between the years of 2000-2005 and 2009-2012 were included in this retrospective study. The information about statin, metformin and alpha-blockers use was recorded immediately prior to treatment. Differences in PSA levels prior to treatment by medication status were estimated using univariate and multivariate linear regression on log PSA values. Results: Compared with men who were not on these medications, the PSA level at presentation was 20% lower for statin users (p = 0.002) and 33% lower for metformin users (p = 0.004). We did not observe statistically significant associations between the use of statins or metformin and cancer stage, National Comprehensive Cancer Network (NCCN) risk score, or therapy outcome. A statistically significant association between the NCCN risk score and the use of alpha-blockers was observed (p = 0.002). Conclusions: We found that statins and metformin were associated with lower PSA levels in prostate cancer patients to an extent that could influence management decisions. We found no statistically significant associations between the use of these medications and treatment outcomes. 展开更多
关键词 PSA STATINS METFORMIN PROSTATE Cancer
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Using Novel Statistical Techniques to Accurately Determine the Predictive Dose Range in a Study of Overall Survival after Definitive Radiotherapy for Stage III Non-Small Cell Lung Cancer in Association with Heart Dose
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作者 Joshua R. Niska Jiuyun Hu +4 位作者 Jing Li Michael G. Herman Cameron S. Thorpe Steven E. Schild mirek fatyga 《Journal of Cancer Therapy》 2021年第9期505-529,共25页
<strong>Purpose:</strong> <span>Recent studies of radiotherapy</span><span "=""> </span><span>(RT) for stage III non-small-cell lung cancer</span><span... <strong>Purpose:</strong> <span>Recent studies of radiotherapy</span><span "=""> </span><span>(RT) for stage III non-small-cell lung cancer</span><span "=""> </span><span>(NSCLC) have associated high dose to the heart with cardiac toxicity</span><span "=""> </span><span>and decreased overall survival</span><span "=""> </span><span>(OS). We used advanced statistical techniques</span><span "=""> </span><span>to account for correlations between dosimetric variables</span><span "=""> </span><span "=""><span>and more accurately determine the range of heart doses which are associated with reduced OS in patients receiving RT for stage III NSCLC.</span><b><span> Methods: </span></b><span>From 2006 to 2013, 119 patients with stage III NSCLC received definitive RT at our institution. OS</span></span><span "=""> </span><span>data was obtained from institutional tumor registry.</span><span "=""> </span><span>We used multivariate Cox model to determine patient specific covariates predictive for reduced overall survival. We examined age, prescription dose, mean lung dose, lung V20, RT technique, stage, chemotherapy, tumor laterality, tumor volume, and tumor site as candidate covariates.</span><span "=""> </span><span>We</span><span "=""> </span><span>subsequently used novel statistical techniques within multivariate Cox model to</span><span "=""> </span><span>systematically search the whole heart dose-volume histogram</span><span "=""> </span><span>(DVH) for dose parameters</span><span "=""> </span><span "=""><span>associated with OS.</span><b><span> Results: </span></b><span>Patients were followed until death or 2.5 to 81.2 months (median 30.4 months) in those alive at last follow up. On multivariate analysis of whole heart DVH</span></span><span>,</span><span> the dose of</span><span "=""> </span><span>51</span><span "=""> </span><span>Gy was identified as a threshold dose above which the dose volume relationship becomes predictive for OS. We identified</span><span "=""> </span><span>V55Gy (percentage of the whole heart volume receiving at least</span><span "=""> </span><span>55</span><span "=""> </span><span>Gy) as the best single DVH index which can be used to set treatment optimization constraints</span><span "=""> </span><span>(Hazard Ratio = 1.044 per 1% increase in heart volume exposed to at least 55</span><span "=""> </span><span>Gy, P</span><span "=""> </span><span>=</span><span "=""> </span><span>0.03). Additional characteristics correlated with OS on multivariate analysis were</span><span "=""> </span><span "=""><span>age, stage (IIIA/IIIB), and administration of chemotherapy. </span><b><span>Conclusion:</span></b><span> Doses above 51</span></span><span "=""> </span><span>Gy, applied to</span><span "=""> </span><span>small volumes of the heart,</span><span "=""> </span><span>are associated with worse OS in stage III NSCLC patients treated with definitive RT. Higher stage, older age and lack of chemotherapy were also associated with reduced OS</span><span>.</span> 展开更多
关键词 Lung Cancer Cardiac Toxicity Lung Radiation Therapy Non-Small Cell Lung Cancer Radiation Toxicity
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Impact of Cardiac Dose on Overall Survival in Lung Stereotactic Body Radiotherapy (SBRT) Compared to Conventionally Fractionated Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC)
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作者 Justin D. Anderson Jiuyun Hu +2 位作者 Jing Li Steven E. Schild mirek fatyga 《Journal of Cancer Therapy》 2021年第7期409-423,共15页
<strong>Purpose:</strong> <span><span><span style="font-family:""><span style="font-family:Verdana;">To examine possible association between heart irradiati... <strong>Purpose:</strong> <span><span><span style="font-family:""><span style="font-family:Verdana;">To examine possible association between heart irradiation and Overall Survival (OS) in lung SBRT patients and to compare observed associations with cardiac toxicity models previously derived in LA-NSCLC patient studies. </span><b><span style="font-family:Verdana;">Materials and Methods: </span></b><span style="font-family:Verdana;">197 Patients treated with lung SBRT at Mayo Clinic Arizona were selected for this IRB</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">approved study. Multivariate Cox model with Akaike Information Criterion (AIC) was used to select patient</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">specific covariates associated with OS. Heart dosimetry was represented by </span></span></span><span><span><i><span style="font-family:""><span style="font-family:Verdana;">V</span><sub><span style="font-family:Verdana;">D</span></sub></span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> indices, which is a percentage of volume exposed to dose D or greater. Multivariate Cox model</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">s</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> with patient</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">specific covariates and single </span></span></span><span><span><i><span style="font-family:""><span style="font-family:Verdana;">V</span><sub><span style="font-family:Verdana;">D</span></sub></span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> index per model was used to find a range of doses which were predictive for OS. A digital subdivision of the heart was further used to determine </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">spatial distribution of doses which were predictive for OS. A coarse subdivision divided heart into 4 segments, while </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">fine subdivision divided heart into 64 segments. Knowledge constrained Fused Lasso operator was used to derive a more complete model which correlated heart dosimetry with OS. Results of statistical analysis were compared to predictions of a model of cardiac toxicity in LA-NSCLC patients.</span><b><span style="font-family:Verdana;"> Results: </span></b><span style="font-family:Verdana;">Higher age (p < 0.001), higher stage (p < 0.001) and squamous cell histology (p = 0.001) were associated with reduced OS. Whole heart DVH analysis did not reveal associations between heart irradiation and reduced OS. Coarse subdivision of the heart into four segments revealed that the irradiation of two inferior segments of the heart with low doses was associated with reduced OS, </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">V</span></i></span></span><span><span><sub><span style="font-family:""><span style="font-family:Verdana;">2</span><i><span style="font-family:Verdana;">Gy</span></i></span></sub></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> in the right-inferior segment (HR = 1.012/1%, p = 0.02), and </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">V</span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><sub><span style="font-family:Verdana;">1</span></sub></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><sub><span style="font-family:Verdana;">Gy</span></sub></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> in the left-inferior segment (HR = 1.01/1%, p = 0.04). Maximum dose in the right-inferior segment of the heart was also associated with reduced OS (HR = 1.02/Gy, p = 0.02). Fine subdivision of the heart into 64 segments revealed that approximately 25% of heart volume in the inferior part of the heart (15/64 segments), when irradiated to doses in the 1</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Gy </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 5</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">Gy range, were predictive for reduced OS (HR = 1.01/1%, p = 0.01). A previously derived model of cardiac toxicity in LA-NSCLC patients did not predict a reduction of OS due to heart irradiation in lung SBRT patients, because of relatively low doses to the heart in most lung SBRT patients. </span><b><span style="font-family:Verdana;">Conclusions:</span></b><span style="font-family:Verdana;"> Doses lower than 5</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Gy in the inferior segments of the heart may be associated with reduced overall survival in patients treated for lung lesions with SBRT. Stage and histology of the disease, as well as patients’ age, were also associated with overall survival. Comparisons of cardiac toxicity patterns in LA-NSCLC patients and lung SBRT patients suggest different etiology of cardiac toxicity in the two groups.</span></span></span> 展开更多
关键词 Lung Cancer Lung SBRT Cardiac Toxicity Lung Radiation Therapy Non-Small Cell Lung Cancer
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