Hyperparathyroidism in pregnancy: options for localization and surgical therapy.

Science.gov (United States)

McMullen, Todd P W; Learoyd, Diana L; Williams, David C; Sywak, Mark S; Sidhu, Stan B; Delbridge, Leigh W

2010-08-01

Hyperparathyroidism in pregnancy is a threat to the health of both mother and fetus. The mothers suffer commonly from nephrolithiasis, hyperemesis, or even hypercalcemic crisis. Untreated disease will commonly complicate fetal development and fetal death is a significant risk. Treatment options, including medical and surgical therapy, are debated in the literature. This is a case series comprising seven patients with primary hyperparathyroidism in pregnancy. Data collected included symptoms at diagnosis, biochemical abnormalities, pathologic findings, treatment regimes, and subsequent maternal and fetal outcomes. Seven women, aged 20 to 39 years, presented with hyperparathyroidism during pregnancy. The earliest presented at 8 weeks and the latest at 38 weeks. Four of seven patients experienced renal calculi. Calcium levels were 2.7-3.5 mmol/l. All were found to have solitary parathyroid adenomas, of which two were in ectopic locations. Fetal complications included three preterm deliveries and one fetal death with no cases of neonatal tetany. Maternal and fetal complications could not be predicted based on duration or severity of hypercalcemia. Three patients were treated during pregnancy with surgery, and two of these had ectopic glands that required reoperations with a novel approach using Tc-99m sestamibi scanning during pregnancy to assist in localizing the abnormal gland. Four cases were treated postpartum with a combination of open and minimally invasive approaches after localization. No operative complications or fetal loss related to surgery were observed in this cohort. Primary hyperparathyroidism in pregnancy represents a significant risk for maternal and fetal complications that cannot be predicted by duration of symptoms or serum calcium levels. Surgical treatment should be considered early, and a minimally invasive approach with ultrasound is best suited to mitigating risk to mother and fetus. Equally important, Tc-99m sestamibi imaging may be used

Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer.

Science.gov (United States)

Cha, Eugene K; Eastham, James A

2015-05-01

Although both surgery and radiation are potential curative options for men with clinically localized prostate cancer, a significant proportion of men with high-risk and locally advanced disease will demonstrate biochemical and potentially clinical progression of their disease. Neoadjuvant systemic therapy before radical prostatectomy (RP) is a logical strategy to improve treatment outcomes for men with clinically localized high-risk prostate cancer. Furthermore, delivery of chemotherapy and other systemic agents before RP affords an opportunity to explore the efficacy of these agents with pathologic end points. Neoadjuvant chemotherapy, primarily with docetaxel (with or without androgen deprivation therapy), has demonstrated feasibility and safety in men undergoing RP, but no study to date has established the efficacy of neoadjuvant chemotherapy or neoadjuvant chemohormonal therapies. Other novel agents, such as those targeting the vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, clusterin, and immunomodulatory therapeutics, are currently under investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

Pak1, adjuvant tamoxifen therapy, and breast cancer recurrence risk in a Danish population-based study

DEFF Research Database (Denmark)

Ahern, Thomas P; Cronin-Fenton, Deirdre P; Lash, Timothy L

2016-01-01

-/TAM - group. Pak1 cytoplasmic intensity was not associated with breast cancer recurrence in either group (ER+/TAM + ORadj for strong vs. no cytoplasmic staining = 0.91, 95% CI 0.57, 1.5; ER-/TAM - ORadj for strong vs. no cytoplasmic staining = 0.74, 95% CI 0.39, 1.4). Associations between Pak1 nuclear......Background Adjuvant tamoxifen therapy approximately halves the risk of estrogen receptor-positive (ER+) breast cancer recurrence, but many women do not respond to therapy. Observational studies nested in clinical trial populations suggest that overexpression or nuclear localization of p21-activated...... by immunohistochemical staining of primary breast tumors from recurrence cases and matched controls from two breast cancer populations; women diagnosed with ER-positive tumors who received at least one year of tamoxifen therapy (ER+/TAM+), and women diagnosed with ER-negative tumors who survived for at least one year...

Radiotherapy and hormone therapy in intermediate risk prostate cancer: a critical review

International Nuclear Information System (INIS)

Franco, Rejane Carolina; Souhami, Luis

2015-01-01

Introduction: The standard treatment for patients with high risk prostate cancer is the combined use of radiation therapy (RT ) and hormone therapy (HT). In regards to patients stratified as intermediate risk, the use of HT associated with RT remains controversial, and its use should be carefully planned and based on available evidence. Objective: To critically assess results of randomized studies published in the literature that associated the use of HT of short duration with an average period of 6 months with RT in the treatment of patients with localized prostate cancer classified as intermediate risk. Method: Only randomized studies comparing these treatments were eligible for this review. A structured search through 'PubMed' was carried out using the terms 'androgen suppression therapy', 'radiotherapy', 'randomized trials', 'phase 3 trials', 'prostate cancer' and 'intermediate risk'. Results: Four randomized studies comparing RT alone to RT plus short course HT were found and selected. The majority of the trials had a mixed population of intermediate and high risk disease and did not include patients with only intermediate risk. Despite that, there appears to be a significant benefit for the combined approach regarding disease-free survival, biochemical free survival and overall survival. Conclusion: The randomized studies published so far suggest improved outcomes for the group of patients receiving RT and short course HT. Data from randomized trials comparing RT alone to RT and short course HT in patients with intermediate risk only are forthcoming. (author)

Long-term Results of Carbon Ion Radiation Therapy for Locally Advanced or Unfavorably Located Choroidal Melanoma: Usefulness of CT-based 2-Port Orthogonal Therapy for Reducing the Incidence of Neovascular Glaucoma

International Nuclear Information System (INIS)

Toyama, Shingo; Tsuji, Hiroshi; Mizoguchi, Nobutaka; Nomiya, Takuma; Kamada, Tadashi; Tokumaru, Sunao; Mizota, Atsushi; Ohnishi, Yoshitaka; Tsujii, Hirohiko

2013-01-01

Purpose: To determine the long-term results of carbon ion radiation therapy (C-ion RT) in patients with choroidal melanoma, and to assess the usefulness of CT-based 2-port irradiation in reducing the risk of neovascular glaucoma (NVG). Methods and Materials: Between January 2001 and February 2012, a total of 116 patients with locally advanced or unfavorably located choroidal melanoma received CT-based C-ion RT. Of these patients, 114 were followed up for more than 6 months and their data analyzed. The numbers of T3 and T2 patients (International Union Against Cancer [UICC], 5th edition) were 106 and 8, respectively. The total dose of C-ion RT varied from 60 to 85 GyE, with each dose given in 5 fractions. Since October 2005, 2-port therapy (51 patients) has been used in an attempt to reduce the risk of NVG. A dose-volume histogram analysis was also performed in 106 patients. Results: The median follow-up was 4.6 years (range, 0.5-10.6 years). The 5-year overall survival, cause-specific survival, local control, distant metastasis-free survival, and eye retention rates were 80.4% (95% confidence interval 89.0%-71.8%), 82.2% (90.6%-73.8%), 92.8% (98.5%-87.1%), 72.1% (81.9%-62.3%), and 92.8% (98.1%-87.5%), respectively. The overall 5-year NVG incidence rate was 35.9% (25.9%-45.9%) and that of 1-port group and 2-port group were 41.6% (29.3%-54.0%) and 13.9% (3.2%-24.6%) with statistically significant difference (P<.001). The dose-volume histogram analysis showed that the average irradiated volume of the iris-ciliary body was significantly lower in the non-NVG group than in the NVG group at all dose levels, and significantly lower in the 2-port group than in the 1-port group at high dose levels. Conclusions: The long-term results of C-ion RT for choroidal melanoma are satisfactory. CT-based 2-port C-ion RT can be used to reduce the high-dose irradiated volume of the iris-ciliary body and the resulting risk of NVG

Long-term Results of Carbon Ion Radiation Therapy for Locally Advanced or Unfavorably Located Choroidal Melanoma: Usefulness of CT-based 2-Port Orthogonal Therapy for Reducing the Incidence of Neovascular Glaucoma

Energy Technology Data Exchange (ETDEWEB)

Toyama, Shingo [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Department of Heavy Particle Therapy and Radiation Oncology, Faculty of Medicine, Saga University, Saga (Japan); Tsuji, Hiroshi, E-mail: h_tsuji@nirs.go.jp [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Mizoguchi, Nobutaka; Nomiya, Takuma; Kamada, Tadashi [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Tokumaru, Sunao [Department of Heavy Particle Therapy and Radiation Oncology, Faculty of Medicine, Saga University, Saga (Japan); Mizota, Atsushi [Department of Ophthalmology, Teikyo University School of Medicine, Tokyo (Japan); Ohnishi, Yoshitaka [Department of Ophthalmology, Wakayama Medical University, Wakayama (Japan); Tsujii, Hirohiko [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan)

2013-06-01

Purpose: To determine the long-term results of carbon ion radiation therapy (C-ion RT) in patients with choroidal melanoma, and to assess the usefulness of CT-based 2-port irradiation in reducing the risk of neovascular glaucoma (NVG). Methods and Materials: Between January 2001 and February 2012, a total of 116 patients with locally advanced or unfavorably located choroidal melanoma received CT-based C-ion RT. Of these patients, 114 were followed up for more than 6 months and their data analyzed. The numbers of T3 and T2 patients (International Union Against Cancer [UICC], 5th edition) were 106 and 8, respectively. The total dose of C-ion RT varied from 60 to 85 GyE, with each dose given in 5 fractions. Since October 2005, 2-port therapy (51 patients) has been used in an attempt to reduce the risk of NVG. A dose-volume histogram analysis was also performed in 106 patients. Results: The median follow-up was 4.6 years (range, 0.5-10.6 years). The 5-year overall survival, cause-specific survival, local control, distant metastasis-free survival, and eye retention rates were 80.4% (95% confidence interval 89.0%-71.8%), 82.2% (90.6%-73.8%), 92.8% (98.5%-87.1%), 72.1% (81.9%-62.3%), and 92.8% (98.1%-87.5%), respectively. The overall 5-year NVG incidence rate was 35.9% (25.9%-45.9%) and that of 1-port group and 2-port group were 41.6% (29.3%-54.0%) and 13.9% (3.2%-24.6%) with statistically significant difference (P<.001). The dose-volume histogram analysis showed that the average irradiated volume of the iris-ciliary body was significantly lower in the non-NVG group than in the NVG group at all dose levels, and significantly lower in the 2-port group than in the 1-port group at high dose levels. Conclusions: The long-term results of C-ion RT for choroidal melanoma are satisfactory. CT-based 2-port C-ion RT can be used to reduce the high-dose irradiated volume of the iris-ciliary body and the resulting risk of NVG.

Neoadjuvant Treatment of High-Risk, Clinically Localized Prostate Cancer Prior to Radical Prostatectomy.

Science.gov (United States)

Pietzak, Eugene J; Eastham, James A

2016-05-01

Multimodal strategies combining local and systemic therapy offer the greatest chance of cure for many with men with high-risk prostate cancer who may harbor occult metastatic disease. However, no systemic therapy combined with radical prostatectomy has proven beneficial. This was in part due to a lack of effective systemic agents; however, there have been several advancements in the metastatic and castrate-resistant prostate cancer that might prove beneficial if given earlier in the natural history of the disease. For example, novel hormonal agents have recently been approved for castration-resistant prostate cancer with some early phase II neoadjuvant showing promise. Additionally, combination therapy with docetaxel-based chemohormonal has demonstrated a profound survival benefit in metastatic hormone-naïve patients and might have a role in eliminating pre-existing ADT-resistant tumor cells in the neoadjuvant setting. The Cancer and Leukemia Group B (CALGB)/Alliance 90203 trial has finished accrual and should answer the question as to whether neoadjuvant docetaxel-based chemohormonal therapy provides an advantage over prostatectomy alone. There are also several promising targeted agents and immunotherapies under investigation in phase I/II trials with the potential to provide benefit in the neoadjuvant setting.

Does menopausal hormone therapy reduce myocardial infarction risk if initiated early after menopause? A population-based case-control study.

Science.gov (United States)

Carrasquilla, Germán D; Berglund, Anita; Gigante, Bruna; Landgren, Britt-Marie; de Faire, Ulf; Hallqvist, Johan; Leander, Karin

2015-06-01

This study aims to assess whether the timing of menopausal hormone therapy initiation in relation to onset of menopause and hormone therapy duration is associated with myocardial infarction risk. This study was based on the Stockholm Heart Epidemiology Program, a population-based case-control study including 347 postmenopausal women who had experienced a nonfatal myocardial infarction and 499 female control individuals matched for age and residential area. Odds ratios (with 95% CIs) for myocardial infarction were calculated using logistic regression. Early initiation of hormone therapy (within 10 y of onset of menopause or before age 60 y), compared with never use, was associated with an odds ratio of 0.87 (95% CI, 0.58-1.30) after adjustments for lifestyle factors, body mass index, and socioeconomic status. For late initiation of hormone therapy, the corresponding odds ratio was 0.97 (95% CI, 0.53-1.76). For hormone therapy duration of 5 years or more, compared with never use, the adjusted odds ratio was 0.64 (95% CI, 0.35-1.18). For hormone therapy duration of less than 5 years, the odds ratio was 0.97 (95% CI, 0.63-1.48). Neither the timing of hormone therapy initiation nor the duration of therapy is significantly associated with myocardial infarction risk.

Outcome According to Elective Pelvic Radiation Therapy in Patients With High-Risk Localized Prostate Cancer: A Secondary Analysis of the GETUG 12 Phase 3 Randomized Trial.

Science.gov (United States)

Blanchard, Pierre; Faivre, Laura; Lesaunier, François; Salem, Naji; Mesgouez-Nebout, Nathalie; Deniau-Alexandre, Elisabeth; Rolland, Frédéric; Ferrero, Jean-Marc; Houédé, Nadine; Mourey, Loïc; Théodore, Christine; Krakowski, Ivan; Berdah, Jean-François; Baciuchka, Marjorie; Laguerre, Brigitte; Davin, Jean-Louis; Habibian, Muriel; Culine, Stéphane; Laplanche, Agnès; Fizazi, Karim

2016-01-01

The role of pelvic elective nodal irradiation (ENI) in the management of prostate cancer is controversial. This study analyzed the role of pelvic radiation therapy (RT) on the outcome in high-risk localized prostate cancer patients included in the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG) 12 trial. Patients with a nonpretreated high-risk localized prostate cancer and a staging lymphadenectomy were randomly assigned to receive either goserelin every 3 months for 3 years and 4 cycles of docetaxel plus estramustine or goserelin alone. Local therapy was administered 3 months after the start of systemic treatment. Performance of pelvic ENI was left to the treating physician. Only patients treated with primary RT were included in this analysis. The primary endpoint was biochemical progression-free survival (bPFS). A total of 413 patients treated from 2002 to 2006 were included, of whom 358 were treated using primary RT. A total of 208 patients received pelvic RT and 150 prostate-only RT. Prostate-specific antigen (PSA) concentration, Gleason score, or T stage did not differ according to performance of pelvic RT; pN+ patients more frequently received pelvic RT than pN0 patients (PENI in multivariate analysis (HR: 1.10 [95% CI: 0.78-1.55], P=.60), even when analysis was restricted to pN0 patients (HR: 0.88 [95% CI: 0.59-1.31], P=.53). Pelvic ENI was not associated with increased acute or late patient reported toxicity. This unplanned analysis of a randomized trial failed to demonstrate a benefit of pelvic ENI on bPFS in high-risk localized prostate cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Local Failure in Resected N1 Lung Cancer: Implications for Adjuvant Therapy

International Nuclear Information System (INIS)

Higgins, Kristin A.; Chino, Junzo P.; Berry, Mark; Ready, Neal; Boyd, Jessamy; Yoo, David S.; Kelsey, Chris R.

2012-01-01

Purpose: To evaluate actuarial rates of local failure in patients with pathologic N1 non–small-cell lung cancer and to identify clinical and pathologic factors associated with an increased risk of local failure after resection. Methods and Materials: All patients who underwent surgery for non–small-cell lung cancer with pathologically confirmed N1 disease at Duke University Medical Center from 1995–2008 were identified. Patients receiving any preoperative therapy or postoperative radiotherapy or with positive surgical margins were excluded. Local failure was defined as disease recurrence within the ipsilateral hilum, mediastinum, or bronchial stump/staple line. Actuarial rates of local failure were calculated with the Kaplan-Meier method. A Cox multivariate analysis was used to identify factors independently associated with a higher risk of local recurrence. Results: Among 1,559 patients who underwent surgery during the time interval, 198 met the inclusion criteria. Of these patients, 50 (25%) received adjuvant chemotherapy. Actuarial (5-year) rates of local failure, distant failure, and overall survival were 40%, 55%, and 33%, respectively. On multivariate analysis, factors associated with an increased risk of local failure included a video-assisted thoracoscopic surgery approach (hazard ratio [HR], 2.5; p = 0.01), visceral pleural invasion (HR, 2.1; p = 0.04), and increasing number of positive N1 lymph nodes (HR, 1.3 per involved lymph node; p = 0.02). Chemotherapy was associated with a trend toward decreased risk of local failure that was not statistically significant (HR, 0.61; p = 0.2). Conclusions: Actuarial rates of local failure in pN1 disease are high. Further investigation of conformal postoperative radiotherapy may be warranted.

Local Failure in Resected N1 Lung Cancer: Implications for Adjuvant Therapy

Energy Technology Data Exchange (ETDEWEB)

Higgins, Kristin A., E-mail: kristin.higgins@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Chino, Junzo P [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Berry, Mark [Department of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke University Medical Center, Durham, NC (United States); Ready, Neal [Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, NC (United States); Boyd, Jessamy [US Oncology, Dallas, TX (United States); Yoo, David S; Kelsey, Chris R [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

2012-06-01

Purpose: To evaluate actuarial rates of local failure in patients with pathologic N1 non-small-cell lung cancer and to identify clinical and pathologic factors associated with an increased risk of local failure after resection. Methods and Materials: All patients who underwent surgery for non-small-cell lung cancer with pathologically confirmed N1 disease at Duke University Medical Center from 1995-2008 were identified. Patients receiving any preoperative therapy or postoperative radiotherapy or with positive surgical margins were excluded. Local failure was defined as disease recurrence within the ipsilateral hilum, mediastinum, or bronchial stump/staple line. Actuarial rates of local failure were calculated with the Kaplan-Meier method. A Cox multivariate analysis was used to identify factors independently associated with a higher risk of local recurrence. Results: Among 1,559 patients who underwent surgery during the time interval, 198 met the inclusion criteria. Of these patients, 50 (25%) received adjuvant chemotherapy. Actuarial (5-year) rates of local failure, distant failure, and overall survival were 40%, 55%, and 33%, respectively. On multivariate analysis, factors associated with an increased risk of local failure included a video-assisted thoracoscopic surgery approach (hazard ratio [HR], 2.5; p = 0.01), visceral pleural invasion (HR, 2.1; p = 0.04), and increasing number of positive N1 lymph nodes (HR, 1.3 per involved lymph node; p = 0.02). Chemotherapy was associated with a trend toward decreased risk of local failure that was not statistically significant (HR, 0.61; p = 0.2). Conclusions: Actuarial rates of local failure in pN1 disease are high. Further investigation of conformal postoperative radiotherapy may be warranted.

Conformal radiation therapy with or without intensity modulation in the treatment of localized prostate cancer

International Nuclear Information System (INIS)

Maingon, P.; Truc, G.; Bosset, M.; Peignaux, K.; Ammor, A.; Bolla, M.

2005-01-01

Conformal radiation therapy has now to be considered as a standard treatment of localized prostatic adenocarcinomas. Using conformational methods and intensity modulated radiation therapy requires a rigorous approach for their implementation in routine, focused on the reproducibility of the treatment, target volume definitions, dosimetry, quality control, setup positioning. In order to offer to the largest number of patients high-dose treatment, the clinicians must integrate as prognostic factors accurate definition of microscopic extension as well as the tolerance threshold of critical organs. High-dose delivery is expected to be most efficient in intermediary risks and locally advanced diseases. Intensity modulated radiation therapy is specifically dedicated to dose escalation. Perfect knowledge of classical constraints of conformal radiation therapy is required. Using such an approach in routine needs a learning curve including the physicists and a specific quality assurance program. (author)

Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors

International Nuclear Information System (INIS)

Boekel, Naomi B.; Schaapveld, Michael; Gietema, Jourik A.; Russell, Nicola S.; Poortmans, Philip; Theuws, Jacqueline C.M.; Schinagl, Dominic A.X.; Rietveld, Derek H.F.; Versteegh, Michel I.M.; Visser, Otto; Rutgers, Emiel J.T.; Aleman, Berthe M.P.; Leeuwen, Flora E. van

2016-01-01

Purpose: To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later. Methods and Materials: A large, population-based cohort comprising 70,230 surgically treated stage I to III BC patients diagnosed before age 75 years between 1989 and 2005 was linked with population-based registries for CVD. Cardiovascular disease risks were compared with the general population, and within the cohort using competing risk analyses. Results: Compared with the general Dutch population, BC patients had a slightly lower CVD mortality risk (standardized mortality ratio 0.92, 95% confidence interval [CI] 0.88-0.97). Only death due to valvular heart disease was more frequent (standardized mortality ratio 1.28, 95% CI 1.08-1.52). Left-sided radiation therapy after mastectomy increased the risk of any cardiovascular event compared with both surgery alone (subdistribution hazard ratio (sHR) 1.23, 95% CI 1.11-1.36) and right-sided radiation therapy (sHR 1.19, 95% CI 1.04-1.36). Radiation-associated risks were found for not only ischemic heart disease, but also for valvular heart disease and congestive heart failure (CHF). Risks were more pronounced in patients aged <50 years at BC diagnosis (sHR 1.48, 95% CI 1.07-2.04 for left- vs right-sided radiation therapy after mastectomy). Left- versus right-sided radiation therapy after wide local excision did not increase the risk of all CVD combined, yet an increased ischemic heart disease risk was found (sHR 1.14, 95% CI 1.01-1.28). Analyses including detailed radiation therapy information showed an increased CVD risk for left-sided chest wall irradiation alone, left-sided breast irradiation alone, and internal mammary chain field irradiation, all compared with right-sided breast irradiation alone. Compared with patients not treated with chemotherapy, chemotherapy used ≥1997 (ie, anthracyline-based chemotherapy) increased the risk of CHF (sHR 1.35, 95% CI 1

Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors

Energy Technology Data Exchange (ETDEWEB)

Boekel, Naomi B.; Schaapveld, Michael [Epidemiology, Netherlands Cancer Institute, Amsterdam (Netherlands); Gietema, Jourik A. [Medical Oncology, University Medical Center Groningen, Groningen (Netherlands); Russell, Nicola S. [Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Poortmans, Philip [Radiation Oncology, Institute Verbeeten, Tilburg (Netherlands); Radiation Oncology, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands); Theuws, Jacqueline C.M. [Radiotherapy, Catharina Hospital Eindhoven, Eindhoven (Netherlands); Schinagl, Dominic A.X. [Radiation Oncology, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands); Rietveld, Derek H.F. [Radiation Oncology, VU University Medical Center Amsterdam, Amsterdam (Netherlands); Versteegh, Michel I.M. [Steering Committee Cardiac Interventions Netherlands, Leiden University Medical Center, Leiden (Netherlands); Visser, Otto [Registration and Research, Comprehensive Cancer Center The Netherlands, Utrecht (Netherlands); Rutgers, Emiel J.T. [Surgery, Netherlands Cancer Institute, Amsterdam (Netherlands); Aleman, Berthe M.P. [Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Leeuwen, Flora E. van, E-mail: f.v.leeuwen@nki.nl [Epidemiology, Netherlands Cancer Institute, Amsterdam (Netherlands)

2016-04-01

Purpose: To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later. Methods and Materials: A large, population-based cohort comprising 70,230 surgically treated stage I to III BC patients diagnosed before age 75 years between 1989 and 2005 was linked with population-based registries for CVD. Cardiovascular disease risks were compared with the general population, and within the cohort using competing risk analyses. Results: Compared with the general Dutch population, BC patients had a slightly lower CVD mortality risk (standardized mortality ratio 0.92, 95% confidence interval [CI] 0.88-0.97). Only death due to valvular heart disease was more frequent (standardized mortality ratio 1.28, 95% CI 1.08-1.52). Left-sided radiation therapy after mastectomy increased the risk of any cardiovascular event compared with both surgery alone (subdistribution hazard ratio (sHR) 1.23, 95% CI 1.11-1.36) and right-sided radiation therapy (sHR 1.19, 95% CI 1.04-1.36). Radiation-associated risks were found for not only ischemic heart disease, but also for valvular heart disease and congestive heart failure (CHF). Risks were more pronounced in patients aged <50 years at BC diagnosis (sHR 1.48, 95% CI 1.07-2.04 for left- vs right-sided radiation therapy after mastectomy). Left- versus right-sided radiation therapy after wide local excision did not increase the risk of all CVD combined, yet an increased ischemic heart disease risk was found (sHR 1.14, 95% CI 1.01-1.28). Analyses including detailed radiation therapy information showed an increased CVD risk for left-sided chest wall irradiation alone, left-sided breast irradiation alone, and internal mammary chain field irradiation, all compared with right-sided breast irradiation alone. Compared with patients not treated with chemotherapy, chemotherapy used ≥1997 (ie, anthracyline-based chemotherapy) increased the risk of CHF (sHR 1.35, 95% CI 1

Contemporary management of men with high-risk localized prostate cancer in the United States.

Science.gov (United States)

Weiner, A B; Matulewicz, R S; Schaeffer, E M; Liauw, S L; Feinglass, J M; Eggener, S E

2017-09-01

Surgery and radiation-based therapies are standard management options for men with clinically localized high-risk prostate cancer (PCa). Contemporary patterns of care are unknown. We hypothesize the use of surgery has steadily increased in more recent years. Using the National Cancer Data Base for 2004-2013, all men diagnosed with high-risk localized PCa were identified using National Comprehensive Cancer Network criteria. Temporal trends in initial management were assessed. Multivariable logistic regression was used to evaluate demographic and clinical factors associated with undergoing radical prostatectomy (RP). In total, 127 391 men were identified. Use of RP increased from 26% in 2004 to 42% in 2013 (adjusted risk ratio (RR) 1.51, 95% CI 1.42-1.60, P<0.001), while external beam radiation therapy (EBRT) decreased from 49% to 42% (P<0.001). African American men had lower odds of undergoing RP (unadjusted rate of 28%, adjusted RR 0.69, 95% CI 0.66-0.72, <0.001) compared to White men (37%). Age was inversely associated with likelihood of receiving RP. Having private insurance was significantly associated with the increased use of RP (vs Medicare, adjusted odds ratio 1.04, 95% CI 1.01-1.08, P=0.015). Biopsy Gleason scores 8-10 with and without any primary Gleason 5 pattern were associated with decreased odds of RP (vs Gleason score ⩽6, both P<0.001). Academic and comprehensive cancer centers were more likely to perform RP compared to community hospitals (both P<0.001). The likelihood of receiving RP for high-risk PCa dramatically increased from 2004 to 2013. By 2013, the use of RP and EBRT were similar. African American men, elderly men and those without private insurance were less likely to receive RP.

Sunitinib Plus Androgen Deprivation and Radiation Therapy for Patients With Localized High-Risk Prostate Cancer: Results From a Multi-institutional Phase 1 Study

International Nuclear Information System (INIS)

Corn, Paul G.; Song, Danny Y.; Heath, Elisabeth; Maier, Jordan; Meyn, Raymond; Kuban, Deborah; DePetrillo, Thomas A.; Mathew, Paul

2013-01-01

Purpose: To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer. Methods and Materials: Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42 fractions to prostate and seminal vesicles). A 3+3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose of sunitinib. Results: Sunitinib at 12.5- and 25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in, and a drug interaction between sunitinib and bicalutamide was suspected. The protocol was revised and concurrent bicalutamide omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3 proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25 mg as reduced dose) completed therapy. Conclusions: The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation therapy for prostate cancer was established. Using a daily dosing regimen with lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of sunitinib is 25 mg daily

Sunitinib Plus Androgen Deprivation and Radiation Therapy for Patients With Localized High-Risk Prostate Cancer: Results From a Multi-institutional Phase 1 Study

Energy Technology Data Exchange (ETDEWEB)

Corn, Paul G., E-mail: pcorn@mdanderson.org [Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Song, Danny Y. [Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland (United States); Heath, Elisabeth; Maier, Jordan [Karmanos Cancer Institute, Wayne State University, Detroit, Michigan (United States); Meyn, Raymond [Department of Experimental Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Kuban, Deborah [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); DePetrillo, Thomas A. [Department of Radiation Oncology, Tufts Medical Center, Boston, Massachusetts (United States); Mathew, Paul, E-mail: pmathew@tuftsmedicalcenter.org [Department of Hematology-Oncology, Tufts Medical Center, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)

2013-07-01

Purpose: To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer. Methods and Materials: Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42 fractions to prostate and seminal vesicles). A 3+3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose of sunitinib. Results: Sunitinib at 12.5- and 25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in, and a drug interaction between sunitinib and bicalutamide was suspected. The protocol was revised and concurrent bicalutamide omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3 proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25 mg as reduced dose) completed therapy. Conclusions: The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation therapy for prostate cancer was established. Using a daily dosing regimen with lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of sunitinib is 25 mg daily.

Local Recurrence After Uveal Melanoma Proton Beam Therapy: Recurrence Types and Prognostic Consequences

International Nuclear Information System (INIS)

Caujolle, Jean-Pierre; Paoli, Vincent; Chamorey, Emmanuel; Maschi, Celia; Baillif, Stéphanie; Herault, Joël; Gastaud, Pierre; Hannoun-Levi, Jean Michel

2013-01-01

Purpose: To study the prognosis of the different types of uveal melanoma recurrences treated by proton beam therapy (PBT). Methods and Materials: This retrospective study analyzed 61 cases of uveal melanoma local recurrences on a total of 1102 patients treated by PBT between June 1991 and December 2010. Survival rates have been determined by using Kaplan-Meier curves. Prognostic factors have been evaluated by using log-rank test or Cox model. Results: Our local recurrence rate was 6.1% at 5 years. These recurrences were divided into 25 patients with marginal recurrences, 18 global recurrences, 12 distant recurrences, and 6 extrascleral extensions. Five factors have been identified as statistically significant risk factors of local recurrence in the univariate analysis: large tumoral diameter, small tumoral volume, low ratio of tumoral volume over eyeball volume, iris root involvement, and safety margin inferior to 1 mm. In the local recurrence-free population, the overall survival rate was 68.7% at 10 years and the specific survival rate was 83.6% at 10 years. In the local recurrence population, the overall survival rate was 43.1% at 10 years and the specific survival rate was 55% at 10 years. The multivariate analysis of death risk factors has shown a better prognosis for marginal recurrences. Conclusion: Survival rate of marginal recurrences is superior to that of the other recurrences. The type of recurrence is a clinical prognostic value to take into account. The influence of local recurrence retreatment by proton beam therapy should be evaluated by novel studies

Local Recurrence After Uveal Melanoma Proton Beam Therapy: Recurrence Types and Prognostic Consequences

Energy Technology Data Exchange (ETDEWEB)

Caujolle, Jean-Pierre, E-mail: ncaujolle@aol.com [Department of Ophthalmology, Saint Roch Hospital, Nice Teaching Hospital, Nice (France); Paoli, Vincent [Department of Ophthalmology, Saint Roch Hospital, Nice Teaching Hospital, Nice (France); Chamorey, Emmanuel [Department of Radiation Oncology, Protontherapy Center, Centre Antoine Lacassagne, Nice (France); Department of Biostatistics and Epidemiology, Centre Antoine Lacassagne, Nice (France); Maschi, Celia; Baillif, Stéphanie [Department of Ophthalmology, Saint Roch Hospital, Nice Teaching Hospital, Nice (France); Herault, Joël [Department of Radiation Oncology, Protontherapy Center, Centre Antoine Lacassagne, Nice (France); Gastaud, Pierre [Department of Ophthalmology, Saint Roch Hospital, Nice Teaching Hospital, Nice (France); Hannoun-Levi, Jean Michel [Department of Radiation Oncology, Protontherapy Center, Centre Antoine Lacassagne, Nice (France)

2013-04-01

Purpose: To study the prognosis of the different types of uveal melanoma recurrences treated by proton beam therapy (PBT). Methods and Materials: This retrospective study analyzed 61 cases of uveal melanoma local recurrences on a total of 1102 patients treated by PBT between June 1991 and December 2010. Survival rates have been determined by using Kaplan-Meier curves. Prognostic factors have been evaluated by using log-rank test or Cox model. Results: Our local recurrence rate was 6.1% at 5 years. These recurrences were divided into 25 patients with marginal recurrences, 18 global recurrences, 12 distant recurrences, and 6 extrascleral extensions. Five factors have been identified as statistically significant risk factors of local recurrence in the univariate analysis: large tumoral diameter, small tumoral volume, low ratio of tumoral volume over eyeball volume, iris root involvement, and safety margin inferior to 1 mm. In the local recurrence-free population, the overall survival rate was 68.7% at 10 years and the specific survival rate was 83.6% at 10 years. In the local recurrence population, the overall survival rate was 43.1% at 10 years and the specific survival rate was 55% at 10 years. The multivariate analysis of death risk factors has shown a better prognosis for marginal recurrences. Conclusion: Survival rate of marginal recurrences is superior to that of the other recurrences. The type of recurrence is a clinical prognostic value to take into account. The influence of local recurrence retreatment by proton beam therapy should be evaluated by novel studies.

Lifetime risk of renal replacement therapy in Europe

DEFF Research Database (Denmark)

van den Brand, Jan A J G; Pippias, Maria; Stel, Vianda S

2017-01-01

Background: Upcoming KDIGO guidelines for the evaluation of living kidney donors are expected to move towards a personal risk-based evaluation of potential donors. We present the age and sex-specific lifetime risk of renal replacement therapy (RRT) for end-stage renal disease in 10 European...

{sup 18}F-Fluorodeoxyglucose/Positron Emission Tomography Predicts Patterns of Failure After Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Bodner, William R. [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Halmos, Balazs; Cheng, Haiying; Perez-Soler, Roman [Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Keller, Steven M. [Department of Cardiothoracic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kalnicki, Shalom; Garg, Madhur [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

2017-02-01

Background: We previously reported that pretreatment positron emission tomography (PET) identifies lesions at high risk for progression after concurrent chemoradiation therapy (CRT) for locally advanced non-small cell lung cancer (NSCLC). Here we validate those findings and generate tumor control probability (TCP) models. Methods: We identified patients treated with definitive, concurrent CRT for locally advanced NSCLC who underwent staging {sup 18}F-fluorodeoxyglucose/PET/computed tomography. Visible hypermetabolic lesions (primary tumors and lymph nodes) were delineated on each patient's pretreatment PET scan. Posttreatment imaging was reviewed to identify locations of disease progression. Competing risks analyses were performed to examine metabolic tumor volume (MTV) and radiation therapy dose as predictors of local disease progression. TCP modeling was performed to describe the likelihood of local disease control as a function of lesion size. Results: Eighty-nine patients with 259 hypermetabolic lesions (83 primary tumors and 176 regional lymph nodes) met the inclusion criteria. Twenty-eight patients were included in our previous report, and the remaining 61 constituted our validation cohort. The median follow-up time was 22.7 months for living patients. In 20 patients, the first site of progression was a primary tumor or lymph node treated with radiation therapy. The median time to progression for those patients was 11.5 months. Data from our validation cohort confirmed that lesion MTV predicts local progression, with a 30-month cumulative incidence rate of 23% for lesions above 25 cc compared with 4% for lesions below 25 cc (P=.008). We found no evidence that radiation therapy dose was associated with local progression risk. TCP modeling yielded predicted 30-month local control rates of 98% for a 1-cc lesion, 94% for a 10-cc lesion, and 74% for a 50-cc lesion. Conclusion: Pretreatment FDG-PET identifies lesions at risk for progression after CRT for

Adjuvant hormone therapy in patients undergoing high-intensity focused ultrasound therapy for locally advanced prostate cancer

Directory of Open Access Journals (Sweden)

A. I. Neimark

2014-01-01

Full Text Available Objective: to evaluate the efficiency and safety of using the luteinizing hormone releasing hormone leuprorelin with the Atrigel delivery system in doses of 7.5, 22.5, and 45 mg as an adjuvant regimen in high- and moderate-risk cancer patients who have received high-intensity focused ultrasound (HIFU therapy.Subjects and methods. Moderate- and high-risk locally advanced prostate cancer (PC patients treated with HIFU (n = 28 and HIFU in combination with hormone therapy during 6 months (n = 31 were examined.Results. The investigation has shown that leuprorelin acetate monotherapy used within 6 months after HIFU therapy can achieve the highest reduction in prostate-specific antigen levels and positively affect the symptoms of the disease. HIFU in combination with androgen deprivation substantially diminishes the clinical manifestations of the disease and improves quality of life in HIFU-treated patients with PC, by reducing the degree of infravesical obstruction (according to uroflowmetric findings and IPSS scores, and causes a decrease in prostate volume as compared to those who have undergone HIFU only. Treatment with leuprorelin having the Atrigel delivery system has demonstrated the low incidence of adverse reactions and good tolerability.

Radiation-Induced Second Cancer Risk Estimates From Radionuclide Therapy

Science.gov (United States)

Bednarz, Bryan; Besemer, Abigail

2017-09-01

The use of radionuclide therapy in the clinical setting is expected to increase significantly over the next decade. There is an important need to understand the radiation-induced second cancer risk associated with these procedures. In this study the radiation-induced cancer risk in five radionuclide therapy patients was investigated. These patients underwent serial SPECT imaging scans following injection as part of a clinical trial testing the efficacy of a 131Iodine-labeled radiopharmaceutical. Using these datasets the committed absorbed doses to multiple sensitive structures were calculated using RAPID, which is a novel Monte Carlo-based 3D dosimetry platform developed for personalized dosimetry. The excess relative risk (ERR) for radiation-induced cancer in these structures was then derived from these dose estimates following the recommendations set forth in the BEIR VII report. The radiation-induced leukemia ERR was highest among all sites considered reaching a maximum value of approximately 4.5. The radiation-induced cancer risk in the kidneys, liver and spleen ranged between 0.3 and 1.3. The lifetime attributable risks (LARs) were also calculated, which ranged from 30 to 1700 cancers per 100,000 persons and were highest for leukemia and the liver for both males and females followed by radiation-induced spleen and kidney cancer. The risks associated with radionuclide therapy are similar to the risk associated with external beam radiation therapy.

Combined high-intensity local treatment and systemic therapy in metastatic head and neck squamous cell carcinoma: An analysis of the National Cancer Data Base.

Science.gov (United States)

Zumsteg, Zachary S; Luu, Michael; Yoshida, Emi J; Kim, Sungjin; Tighiouart, Mourad; David, John M; Shiao, Stephen L; Mita, Alain C; Scher, Kevin S; Sherman, Eric J; Lee, Nancy Y; Ho, Allen S

2017-12-01

There is increasing evidence that primary tumor ablation can improve survival for some cancer patients with distant metastases. This may be particularly applicable to head and neck squamous cell carcinoma (HNSCC) because of its tropism for locoregional progression. This study included patients with metastatic HNSCC undergoing systemic therapy identified in the National Cancer Data Base. High-intensity local treatment was defined as radiation doses ≥ 60 Gy or oncologic resection of the primary tumor. Multivariate Cox regression, propensity score matching, landmark analysis, and subgroup analysis were performed to account for imbalances in covariates, including adjustments for the number and location of metastatic sites in the subset of patients with this information available. In all, 3269 patients were included (median follow-up, 51.5 months). Patients undergoing systemic therapy with local treatment had improved survival in comparison with patients receiving systemic therapy alone in propensity score-matched cohorts (2-year overall survival, 34.2% vs 20.6%; P treatment, whereas those receiving lower-intensity local treatment had survival similar to that of patients receiving systemic therapy without local treatment. The impact of high-intensity local therapy was time-dependent, with a stronger impact within the first 6 months after the diagnosis (adjusted hazard ratio [AHR], 0.255; 95% confidence interval [CI], 0.210-0.309; P treatment warrants prospective evaluation for select patients with metastatic HNSCC. Cancer 2017;123:4583-4593. © 2017 American Cancer Society. © 2017 American Cancer Society.

Propensity Score Matched Comparison of Intensity Modulated Radiation Therapy vs Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Survival Analysis from the National Cancer Database

Directory of Open Access Journals (Sweden)

Anthony Ricco

2017-08-01

Full Text Available PurposeNo direct comparisons between extreme hypofractionation and conventional fractionation have been reported in randomized trials for the treatment of localized prostate cancer. The goal of this study is to use a propensity score matched (PSM analysis with the National Cancer Database (NCDB for the comparison of stereotactic body radiation therapy (SBRT and intensity modulated radiation therapy (IMRT for organ confined prostate cancer.MethodsMen with localized prostate cancer treated with radiation dose ≥72 Gy for IMRT and ≥35 Gy for SBRT to the prostate only were abstracted from the NCDB. Men treated with previous surgery, brachytherapy, or proton therapy were excluded. Matching was performed to eliminate confounding variables via PSM. Simple 1–1 nearest neighbor matching resulted in a matched sample of 5,430 (2,715 in each group. Subset analyses of men with prostate-specific antigen (PSA > 10, GS = 7, and GS > 7 yielded matched samples of 1,020, 2,194, and 247, respectively.ResultsNo difference in survival was noted between IMRT and SBRT at 8 years (p = 0.65. Subset analyses of higher risk men with PSA > 10 or GS = 7 histology or GS > 7 histology revealed no difference in survival between IMRT and SBRT (p = 0.58, p = 0.68, and p = 0.62, respectively. Variables significant for survival for the matched group included: age (p < 0.0001, primary payor (p = 0.0001, Charlson/Deyo Score (p = 0.0002, PSA (p = 0.0013, Gleason score (p < 0.0001, and use of hormone therapy (p = 0.02.ConclusionUtilizing the NCDB, there is no difference in survival at 8 years comparing IMRT to SBRT in the treatment of localized prostate cancer. Subset analysis confirmed no difference in survival even for intermediate- and high-risk patients based on Gleason Score and PSA.

A quality risk management model approach for cell therapy manufacturing.

Science.gov (United States)

Lopez, Fabio; Di Bartolo, Chiara; Piazza, Tommaso; Passannanti, Antonino; Gerlach, Jörg C; Gridelli, Bruno; Triolo, Fabio

2010-12-01

International regulatory authorities view risk management as an essential production need for the development of innovative, somatic cell-based therapies in regenerative medicine. The available risk management guidelines, however, provide little guidance on specific risk analysis approaches and procedures applicable in clinical cell therapy manufacturing. This raises a number of problems. Cell manufacturing is a poorly automated process, prone to operator-introduced variations, and affected by heterogeneity of the processed organs/tissues and lot-dependent variability of reagent (e.g., collagenase) efficiency. In this study, the principal challenges faced in a cell-based product manufacturing context (i.e., high dependence on human intervention and absence of reference standards for acceptable risk levels) are identified and addressed, and a risk management model approach applicable to manufacturing of cells for clinical use is described for the first time. The use of the heuristic and pseudo-quantitative failure mode and effect analysis/failure mode and critical effect analysis risk analysis technique associated with direct estimation of severity, occurrence, and detection is, in this specific context, as effective as, but more efficient than, the analytic hierarchy process. Moreover, a severity/occurrence matrix and Pareto analysis can be successfully adopted to identify priority failure modes on which to act to mitigate risks. The application of this approach to clinical cell therapy manufacturing in regenerative medicine is also discussed. © 2010 Society for Risk Analysis.

The Environmental Virtual Observatory (EVO) local exemplar: A cloud based local landscape learning visualisation tool for communicating flood risk to catchment stakeholders

Science.gov (United States)

Wilkinson, Mark; Beven, Keith; Brewer, Paul; El-khatib, Yehia; Gemmell, Alastair; Haygarth, Phil; Mackay, Ellie; Macklin, Mark; Marshall, Keith; Quinn, Paul; Stutter, Marc; Thomas, Nicola; Vitolo, Claudia

2013-04-01

Today's world is dominated by a wide range of informatics tools that are readily available to a wide range of stakeholders. There is growing recognition that the appropriate involvement of local communities in land and water management decisions can result in multiple environmental, economic and social benefits. Therefore, local stakeholder groups are increasingly being asked to participate in decision making alongside policy makers, government agencies and scientists. As such, addressing flooding issues requires new ways of engaging with the catchment and its inhabitants at a local level. To support this, new tools and approaches are required. The growth of cloud based technologies offers new novel ways to facilitate this process of exchange of information in earth sciences. The Environmental Virtual Observatory Pilot project (EVOp) is a new initiative from the UK Natural Environment Research Council (NERC) designed to deliver proof of concept for new tools and approaches to support the challenges as outlined above (http://www.evo-uk.org/). The long term vision of the Environmental Virtual Observatory is to: • Make environmental data more visible and accessible to a wide range of potential users including public good applications; • Provide tools to facilitate the integrated analysis of data, greater access to added knowledge and expert analysis and visualisation of the results; • Develop new, added-value knowledge from public and private sector data assets to help tackle environmental challenges. As part of the EVO pilot, an interactive cloud based tool has been developed with local stakeholders. The Local Landscape Visualisation Tool attempts to communicate flood risk in local impacted communities. The tool has been developed iteratively to reflect the needs, interests and capabilities of a wide range of stakeholders. This tool (assessable via a web portal) combines numerous cloud based tools and services, local catchment datasets, hydrological models and

Chemothermal Therapy for Localized Heating and Ablation of Tumor

Directory of Open Access Journals (Sweden)

Zhong-Shan Deng

2013-01-01

Full Text Available Chemothermal therapy is a new hyperthermia treatment on tumor using heat released from exothermic chemical reaction between the injected reactants and the diseased tissues. With the highly minimally invasive feature and localized heating performance, this method is expected to overcome the ubiquitous shortcomings encountered by many existing hyperthermia approaches in ablating irregular tumor. This review provides a relatively comprehensive review on the latest advancements and state of the art in chemothermal therapy. The basic principles and features of two typical chemothermal ablation strategies (acid-base neutralization-reaction-enabled thermal ablation and alkali-metal-enabled thermal/chemical ablation are illustrated. The prospects and possible challenges facing chemothermal ablation are analyzed. The chemothermal therapy is expected to open many clinical possibilities for precise tumor treatment in a minimally invasive way.

Outcome and Toxicity of an Ifosfamide-Based Soft Tissue Sarcoma Treatment Protocol in Children. The Importance of Local Therapy

Directory of Open Access Journals (Sweden)

S. Murray Yule

1998-01-01

Full Text Available Background. Although the survival of children with soft tissue sarcoma (STS has improved considerably, the outcome of patients with metastatic disease, and those with primary tumours of the extremities or parameningeal sites remains disappointing. We describe the clinical outcome of an ifosfamide-based regimen with local therapy directed only to children who failed to achieve a complete response to initial chemotherapy.

Risk management of radiation therapy. Survey by north Japan radiation therapy oncology group

International Nuclear Information System (INIS)

Aoki, Masahiko; Abe, Yoshinao; Yamada, Shogo; Hareyama, Masato; Nakamura, Ryuji; Sugita, Tadashi; Miyano, Takashi

2004-01-01

A North Japan Radiation Oncology Group (NJRTOG) survey was carried out to disclose the risk management of radiation therapy. During April 2002, we sent questionnaires to radiation therapy facilities in northern Japan. There were 31 replies from 27 facilities. Many incidents and accidents were reported, including old cases. Although 60% of facilities had a risk management manual and/or risk manager, only 20% had risk management manuals for radiation therapy. Eighty five percent of radiation oncologists thought that incidents may be due to a lack of manpower. Ninety percent of radiation oncologists want to know the type of cases happened in other facilities. The risk management system is still insufficient for radiation therapy. We hope that our data will be a great help to develop risk management strategies for radiation therapy for all radiation oncologists in Japan. (author)

Combination antiretroviral therapy and cancer risk

DEFF Research Database (Denmark)

Borges, Álvaro H

2017-01-01

PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignanci......ART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.......PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies...... into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk...

Dyslipidemias and Elevated Cardiovascular Risk on Lopinavir-Based Antiretroviral Therapy in Cambodia

Science.gov (United States)

Ly, Sowath; Ouk, Vara; Chanroeurn, Hak; Thavary, Saem; Boroath, Ban; Canestri, Ana; Viretto, Gérald; Delfraissy, Jean-François; Ségéral, Olivier

2016-01-01

Background Lopinavir/ritonavir (LPV/r) is widely used in Cambodia with high efficacy but scarce data exist on long-term metabolic toxicity. Methods We carried out a cross-sectional and retrospective study evaluating metabolic disorders and cardiovascular risk in Cambodian patients on LPV/r-based antiretroviral therapy (ART) for > 1 year followed in Calmette Hospital, Phnom Penh. Data collected included cardiovascular risk factors, fasting blood lipids and glucose, and retrospective collection of bioclinical data. We estimated the 10-year risks of coronary heart disease with the Framingham, Ramathibodi-Electricity Generating Authority of Thailand (Rama-EGAT), and the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) risk equations. We identified patients with LDL above targets defined by the French expert group on HIV and by the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group (IDSA-AACTG). Results Of 115 patients enrolled—mean age 40.9 years, 69.2% male, mean time on LPV/r 3.8 years—40 (34.8%) had hypercholesterolemia (> 2.40 g/L), and 69 (60.0%) had low HDL cholesterol (dyslipidemia was high in this cohort of HIV-infected Cambodian patients on LPV/r. Roughly one third had high LDL levels requiring specific intervention. PMID:27579612

The role of local estrogen therapy in the management of pelvic floor disorders.

Science.gov (United States)

Tzur, T; Yohai, D; Weintraub, A Y

2016-04-01

Pelvic floor disorders are common and bothersome problems that include a variety of conditions. These conditions greatly affect the performance of daily activities and social function such as work, traveling, physical exercise, sleep and sexual function. Aging is a well-known factor affecting the pelvic floor and lower urinary tract anatomy and function. It is clear that the pelvic organs and their surrounding muscular and connective tissue support are estrogen-responsive. Treatment of pelvic floor disorders requires significant health-care resources and their impact is likely to increase in the near future. This literature review aims to provide an overview of both research and clinical aspects of the pathophysiology of urogenital estrogen deficiency and the role of local estrogen therapy as part of the management strategy of different pelvic floor disorders. The safety and risk concerns regarding the use of local estrogen therapy are addressed as well.

Conservative treatment of rectal cancer with local excision and postoperative radiation therapy

International Nuclear Information System (INIS)

Minsky, B.D.

1995-01-01

The conventional surgical treatment for patients with potentially curable transmural and/or node positive rectal cancer is a low anterior resection or abdominoperineal resection. Recently, there has been increasing interest in the use of local excision and postoperative radiation therapy as primary therapy for selected rectal cancers. The limited data suggest that the approach of local excision and postoperative radiation therapy should be limited to patients with either T 1 tumours with adverse pathological factors or T 2 tumours. Transmural tumours, which have a 24% local failure rate, are treated more effectively with standard surgery and pre- or postoperative therapy. The results of local excision and postoperative radiation therapy are encouraging, but more experience is needed to determine if this approach ultimately has similar local control and survival rates as standard surgery. (author)

Intensity-Modulated Radiation Therapy in the Salvage of Locally Recurrent Nasopharyngeal Carcinoma

International Nuclear Information System (INIS)

Qiu Sufang; Lin Shaojun; Tham, Ivan W.K.; Pan Jianji; Lu Jun; Lu, Jiade J.

2012-01-01

Purpose: Local recurrences of nasopharyngeal carcinoma (NPC) may be salvaged by reirradiation with conventional techniques, but with significant morbidity. Intensity-modulated radiation therapy (IMRT) may improve the therapeutic ratio by reducing doses to normal tissue. The aim of this study was to address the efficacy and toxicity profile of IMRT for a cohort of patients with locally recurrent NPC. Methods and Materials: Between August 2003 and June 2009, 70 patients with radiologic or pathologically proven locally recurrent NPC were treated with IMRT. The median time to recurrence was 30 months after the completion of conventional radiation to definitive dose. Fifty-seven percent of the tumors were classified asrT3–4. The minimum planned doses were 59.4 to 60 Gy in 1.8- to 2-Gy fractions per day to the gross disease with margins, with or without chemotherapy. Results: The median dose to the recurrent tumor was 70 Gy (range, 50–77.4 Gy). Sixty-five patients received the planned radiation therapy; 5 patients received between 50 and 60 Gy because of acute side effects. With a median follow-up time of 25 months, the rates of 2-year locoregional recurrence-free survival, disease-free survival, and overall survival were 65.8%, 65.8%, and 67.4%, respectively. Moderate to severe late toxicities were noted in 25 patients (35.7%). Eleven patients (15.7%) had posterior nasal space ulceration, 17 (24.3%) experienced cranial nerve palsies, 12 (17.1%) had trismus, and 12 (17.1%) experienced deafness. Extended disease-free interval (relative risk 2.049) and advanced T classification (relative risk 3.895) at presentation were adverse prognostic factors. Conclusion: Reirradiation with IMRT provides reasonable long-term control in patients with locally recurrent NPC.

Radiation therapy for localized prostate cancer

International Nuclear Information System (INIS)

Taylor, W.J.; Richardson, G.; Hafermann, M.D.

1979-01-01

Since 1965, 401 patients with prostate cancer have received intensive local pelvic radiation therapy at the Virginia Mason Medical Center. Two hundred twenty-one of this series were in the Stage C category. The 36 Stage B cancers were either medically nonoperable, or advanced extent, or had high-grade histopathology. Ten patients each were in diffuse Stage A or Stage D groups, the latter receiving local palliative inensive treatment to the prostate area. The mean age of the patients was 67.6 years. The five year survival of the Stage C group was 57.7%. There was no apparent influence on the survival of irradiated Stage C patients who received estrogen therapy. Current treatment techniques employ 10 megavolt photon beam with whole pelvic nodal fields and bilateral are rotational boost fields. The incidence of reactions and complications is presented

Identification of Patients at Very Low Risk of Local Recurrence After Breast-Conserving Surgery

Energy Technology Data Exchange (ETDEWEB)

Smith, Sally L., E-mail: ssmith11@bccancer.bc.ca [Radiation Therapy Program and Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver Island Centre, University of British Columbia, Victoria, British Columbia (Canada); Truong, Pauline T. [Radiation Therapy Program and Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver Island Centre, University of British Columbia, Victoria, British Columbia (Canada); Lu, Linghong; Lesperance, Mary [Department of Mathematics and Statistics, University of Victoria, Victoria, British Columbia (Canada); Olivotto, Ivo A. [Division of Radiation Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta (Canada)

2014-07-01

Purpose: To identify clinical and pathological factors that identify groups of women with stage I breast cancer with a 5-year risk of local recurrence (LR) ≤1.5% after breast-conserving therapy (BCS) plus whole-breast radiation therapy (RT). Methods and Materials: Study subjects were 5974 patients ≥50 years of age whose cancer was diagnosed between 1989 and 2006, and were referred with pT1 pN0 invasive breast cancer treated with BCS and RT. Cases of 5- and 10-year LR were examined using Kaplan-Meier methods. Recursive partitioning analysis was performed in patients treated with and without endocrine therapy to identify combinations of factors associated with a 5-year LR risk ≤1.5%. Results: The median follow-up was 8.61 years. Median age was 63 years of age (range, 50 to 91). Overall 5-year LR was 1.5% (95% confidence interval [CI], 1.2%-1.9%) and 10-year LR was 3.4% (95% CI, 2.8%-4.0%). Of 2830 patients treated with endocrine therapy, patient subsets identified with 5-year LR ≤1.5% included patients with grade 1 histology (n=1038; LR, 0.2%; 95% CI, 0%-0.5%) or grade 2 histology plus ≥60 years of age (n=843; LR, 0.5%; 95% CI, 0%-1.0%). Ten-year LR for these groups were 0.8% (95% CI, 0.1%-1.6%) and 0.9% (95% CI, 0.2%-1.6%), respectively. Of 3144 patients treated without endocrine therapy, patients with grade 1 histology plus clear margins had 5-year LR ≤1.5% (n=821; LR, 0.6%; 95% CI, 0.1%-1.2%). Ten-year LR for this group was 2.2% (95% CI, 1.0%-3.4%). Conclusions: Histologic grade, age, margin status, and use of endocrine therapy identified 45% of a population-based cohort of female patients over age 50 with stage I breast cancer with a 5-year LR risk ≤1.5% after BCS plus RT. Prospective study is needed to evaluate the safety of omitting RT in patients with such a low risk of LR.

Risk-optimized proton therapy to minimize radiogenic second cancers

DEFF Research Database (Denmark)

Rechner, Laura A; Eley, John G; Howell, Rebecca M

2015-01-01

Proton therapy confers substantially lower predicted risk of second cancer compared with photon therapy. However, no previous studies have used an algorithmic approach to optimize beam angle or fluence-modulation for proton therapy to minimize those risks. The objectives of this study were...... to demonstrate the feasibility of risk-optimized proton therapy and to determine the combination of beam angles and fluence weights that minimizes the risk of second cancer in the bladder and rectum for a prostate cancer patient. We used 6 risk models to predict excess relative risk of second cancer. Treatment...

Proton Therapy for Skull Base Chordomas: An Outcome Study from the University of Florida Proton Therapy Institute

OpenAIRE

Deraniyagala, Rohan L.; Yeung, Daniel; Mendenhall, William M.; Li, Zuofeng; Morris, Christopher G.; Mendenhall, Nancy P.; Okunieff, Paul; Malyapa, Robert S.

2013-01-01

Objectives Skull base chordoma is a rare, locally aggressive tumor located adjacent to critical structures. Gross total resection is difficult to achieve, and proton therapy has the conformal advantage of delivering a high postoperative dose to the tumor bed. We present our experience using proton therapy to treat 33 patients with skull base chordomas.

Platinum-based chemotherapy followed by radiation therapy of locally advanced nasopharyngeal cancer; A retrospective analysis of 39 cases

Energy Technology Data Exchange (ETDEWEB)

Fountzilas, G.; Danilidis, J.; Kosmidis, P.; Srihar, K.S.; Kalogera-Fountzila, A.; Nicolaou, A.; Makrantonakis, P.; Banis, K.; Dimitriadis, A.; Sombolos, K.; Zaramboukas, T.; Themelis, C.; Vritsios, A.; Tourkantonis, A. (Ahepa Univ. Hospital, Thessaloniki (Greece) Metaxa Cancer Hospital, Piraeaus (Greece) Miami School of Medicine and VA Hospital, FL (United States). Sylvester Comprehensive Cancer Center)

1991-01-01

A retrospective analysis was performed of 39 patients with locally advanced nasopharyngeal cancer treated with combined chemotherapy and radiation therapy during the last five years at our departments. There were 26 men and 13 women with median age 55 (24-75) years. Histology was squamous cell carcinoma in 6 patients and undifferentiated carcinoma in the remaining 33 patients. Induction chemotherapy consisted of either regimen A (cisplating 100 mg/m{sup 2} day 1, 5-FU 1000 mg/m{sup 2} days 2-6 as continuous infusion, bleomycin 15 mg days 15 and 29 i.m., mitomycin 4 mg/m{sup 2} day 22 and hydroxyurea 1000 mg/m{sup 2} daily days 23-27) or regimen B (carboplatin 300 mg/m{sup 2} day 1, 5-FU 1000 mg/m{sup 2} days 1-5 as continuous infusion and methotrexate 1.2 g/m{sup 2} day 14 with leucovorin rescue). After completion of induction chemotherapy 13 patients (33%) had complete remission (CR) and 19 (49%) partial remission (PR). The CR rate was increased after radiation therapy to 72%. Survival rates were 88% at 12 and 78% at 24 months. Median time to progression was 29.5 months. In conclusion, induction chemotherapy with a platinum-based regimen followed by radiation therapy achieved a high rate of local control. If the treatment also prolongs survival must, however, be studied by randomized trials. (orig.).

Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

Directory of Open Access Journals (Sweden)

Lima Carmen SP

2011-03-01

Full Text Available Abstract Background Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting. Methods Randomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy versus no active treatment after surgery among renal cell cancer patients. Outcomes were overall survival (OS, disease-free survival (DFS, and severe toxicities. Risk ratios (RR, hazard ratios (HR and 95% confidence intervals were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by I2. Different strategies of adjuvant treatment were evaluated separately. Results Ten studies (2,609 patients were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I2 = 0% or DFS (HR 1.03; 95%CI 0.87 to 1.21; P = 0.77 I2 = 15% when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy and hormone therapy had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group. Conclusions This analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients although they increase the risk of toxic effects. Randomized trials are underway to test targeted therapies, which might open a new therapeutic frontier. Until these trials yield results, no adjuvant therapy can be recommended for patients who undergo surgical resection for renal cell cancer.

Weighing the Anti-Ischemic Benefits and Bleeding Risks from Aspirin Therapy: a Rational Approach.

Science.gov (United States)

Dugani, Sagar; Ames, Jeffrey M; Manson, JoAnn E; Mora, Samia

2018-02-21

The role of aspirin in secondary cardiovascular prevention is well understood; however, the role in primary prevention is less clear, and requires careful balancing of potential benefits with risks. Here, we summarize the evidence base on the benefits and risks of aspirin therapy, discuss clinical practice guidelines and decision support tools to assist in initiating aspirin therapy, and highlight ongoing trials that may clarify the role of aspirin in cardiovascular disease prevention. In 2016, the USPSTF released guidelines on the use of aspirin for primary prevention. Based on 11 trials (n = 118,445), aspirin significantly reduced all-cause mortality and nonfatal myocardial infarction, and in 7 trials that evaluated aspirin ≤ 100 mg/day, there was significant reduction in nonfatal stroke. The USPSTF recommends individualized use of aspirin based on factors including age, 10-year atherosclerotic cardiovascular disease risk score, and bleeding risk. Several ongoing trials are evaluating the role of aspirin in primary prevention, secondary prevention, and in combination therapy for atrial fibrillation. Evidence-based approaches to aspirin use should consider the anti-ischemic benefits and bleeding risks from aspirin. In this era of precision medicine, tools that provide the personalized benefit to risk assessment, such as the freely available clinical decision support tool (Aspirin-Guide), can be easily incorporated into the electronic health record and facilitate more informed decisions about initiating aspirin therapy for primary prevention. Aspirin has a complex matrix of benefits and risks, and its use in primary prevention requires individualized decision-making. Results from ongoing trials may guide healthcare providers in identifying appropriate candidates for aspirin therapy.

Interactive Decision-Support Tool for Risk-Based Radiation Therapy Plan Comparison for Hodgkin Lymphoma

DEFF Research Database (Denmark)

Brodin, N. Patrik; Maraldo, Maja V.; Aznar, Marianne C.

2014-01-01

PURPOSE: To present a novel tool that allows quantitative estimation and visualization of the risk of various relevant normal tissue endpoints to aid in treatment plan comparison and clinical decision making in radiation therapy (RT) planning for Hodgkin lymphoma (HL). METHODS AND MATERIALS...... and a volumetric modulated arc therapy plan for a patient with mediastinal HL. CONCLUSION: This multiple-endpoint decision-support tool provides quantitative risk estimates to supplement the clinical judgment of the radiation oncologist when comparing different RT options....... of dose-response curves to drive the reoptimization of a volumetric modulated arc therapy treatment plan for an HL patient with head-and-neck involvement. We also use this decision-support tool to visualize and quantitatively evaluate the trade-off between a 3-dimensional conformal RT plan...

The role of p53 in radiation therapy outcomes for favorable-to-intermediate-risk prostate cancer

International Nuclear Information System (INIS)

Ritter, Mark A.; Gilchrist, Kennedy W.; Voytovich, Marta; Chappell, Richard J.; Verhoven, Bret M.

2002-01-01

Purpose: Some prostate cancers may have molecular alterations that render them less responsive to radiation therapy; identification of these alterations before treatment might allow improved treatment optimization. This study investigated whether p53, a potential molecular determinant, could predict long-term radiation therapy outcome in a restricted group of relatively favorable-risk prostate cancer patients treated uniformly with irradiation alone. Methods and Materials: This study included 53 patients previously treated with radiotherapy for favorable-to-intermediate-risk prostate cancer. These patients were selected for relatively low pretreatment PSAs (≤21 ng/mL) and Gleason scores (≤7) to decrease the likelihood of nonlocalized disease, because disease localization was necessary to examine the efficacy of localized radiation therapy. The status of p53 was immunohistochemically assessed in paraffin-embedded pretreatment biopsy specimens, along with appropriate controls. This marker was selected based upon a usable mutation prevalence in early-stage prostate cancer and its potential linkage with radiation response via cell cycle, DNA repair, and cell death pathways. Correlation between p53 mutation and clinical outcome was analyzed in univariate and multivariate fashion and included conventional prognosticators, such as stage, grade, and PSA. Freedom from biochemical failure was determined using American Society for Therapeutic Radiology and Oncology criteria. Limitations of prior studies were potentially avoided by requiring adequate posttreatment follow-up (median follow-up in nonfailing patients of 5.1 years), as well as pretreatment PSA and Gleason scores that suggested localized disease, and uniformity of treatment. Results: The total group of 53 favorable-to-intermediate-risk patients demonstrated an actuarial biochemical failure rate of 35% at 5 years. Forty percent of all specimens had a greater than 10% labeling index for p53 mutation, and

Excellent local tumor response after fractionated stereotactic radiation therapy for locally recurrent nasopharynx cancer

International Nuclear Information System (INIS)

Ahn, Y. C.; Lim, D. H.; Choi, D. R.; Kim, D. K.; Kim, D. Y.; Huh, S. J.; Baek, C. H.; Chu, K. C.; Yoon, S. S.; Park, K. C.

1997-01-01

This study is to report experience with Fractionated Stereotactic Radiation Therapy (FSRT) for locally recurrent nasopharynx cancer after curative conventional radiation therapy. Three patients with locally recurrent and symptomatic nasopharynx cancer were given FSRT as reirradiation method between the period of September of 1995 and August of 1996. For two patients, application of FSRT is their third radiation therapy directed to the nasopharynx. Two patients were given low dose chemotherapy as radiation sensitizer concurrently with FSRT. Authors used 3-dimensional coordinate system by individually made, relocatable Gill-Thomas-Cosman (GTC) stereotactic frame and multiple non-coplanar arc therapy dose planning was done using XKnife-3. Total of 45 Gy/18 fractions or 50 Gy/20 fractions were given. Authors observed satisfactory symptomatic improvement and remarkable objective tumor size decrease by follow-up MR images taken 1 month post-FSRT in all three patients, while no neurologic side effect attributable to reirradiation was noticed. Two died at 7 and 9 months with loco-regional and distant seeding outside FSRT field, while one patient is living for 4 month. Authors experienced satisfactory therapeutic effectiveness and safety of FSRT as reirradiation method for locally recurrent nasopharynx cancer. Development of more effective systemic chemotherapeutic regimen is desired for distant metastasis. (author)

Loss of Nuclear Localized and Tyrosine Phosphorylated Stat5 in Breast Cancer Predicts Poor Clinical Outcome and Increased Risk of Antiestrogen Therapy Failure

Science.gov (United States)

Peck, Amy R.; Witkiewicz, Agnieszka K.; Liu, Chengbao; Stringer, Ginger A.; Klimowicz, Alexander C.; Pequignot, Edward; Freydin, Boris; Tran, Thai H.; Yang, Ning; Rosenberg, Anne L.; Hooke, Jeffrey A.; Kovatich, Albert J.; Nevalainen, Marja T.; Shriver, Craig D.; Hyslop, Terry; Sauter, Guido; Rimm, David L.; Magliocco, Anthony M.; Rui, Hallgeir

2011-01-01

Purpose To investigate nuclear localized and tyrosine phosphorylated Stat5 (Nuc-pYStat5) as a marker of prognosis in node-negative breast cancer and as a predictor of response to antiestrogen therapy. Patients and Methods Levels of Nuc-pYStat5 were analyzed in five archival cohorts of breast cancer by traditional diaminobenzidine-chromogen immunostaining and pathologist scoring of whole tissue sections or by immunofluorescence and automated quantitative analysis (AQUA) of tissue microarrays. Results Nuc-pYStat5 was an independent prognostic marker as measured by cancer-specific survival (CSS) in patients with node-negative breast cancer who did not receive systemic adjuvant therapy, when adjusted for common pathology parameters in multivariate analyses both by standard chromogen detection with pathologist scoring of whole tissue sections (cohort I; n = 233) and quantitative immunofluorescence of a tissue microarray (cohort II; n = 291). Two distinct monoclonal antibodies gave concordant results. A progression array (cohort III; n = 180) revealed frequent loss of Nuc-pYStat5 in invasive carcinoma compared to normal breast epithelia or ductal carcinoma in situ, and general loss of Nuc-pYStat5 in lymph node metastases. In cohort IV (n = 221), loss of Nuc-pYStat5 was associated with increased risk of antiestrogen therapy failure as measured by univariate CSS and time to recurrence (TTR). More sensitive AQUA quantification of Nuc-pYStat5 in antiestrogen-treated patients (cohort V; n = 97) identified by multivariate analysis patients with low Nuc-pYStat5 at elevated risk for therapy failure (CSS hazard ratio [HR], 21.55; 95% CI, 5.61 to 82.77; P < .001; TTR HR, 7.30; 95% CI, 2.34 to 22.78; P = .001). Conclusion Nuc-pYStat5 is an independent prognostic marker in node-negative breast cancer. If confirmed in prospective studies, Nuc-pYStat5 may become a useful predictive marker of response to adjuvant hormone therapy. PMID:21576635

Art Therapy Programs with At-Risk Students in Public Schools

Science.gov (United States)

Varallo, Patrick A.

2012-01-01

Educating and meeting the multiple needs of students at risk of low academic achievement has been a growing concern for public schools in the United States. Many at-risk students require alternative school-based interventions. This study examined the operation, premise, and objectives of art therapy integrated in 14 school districts across the…

The role local initiatives in community based disaster risk management in Kemijen, Semarang City

Science.gov (United States)

Fauzie, W. Z.; Sariffudin, S.

2017-06-01

Community-based disaster risk reduction is one of the homegrown initiatives efforts and community empowerment oriented in disaster management. This approach is very important because no one can understand the conditions in a region better than the local communities. Therefore, the implementation of CBDRM always emphasize local initiatives in decision making. The existence of local initiative is necessary specially to anticipate the impact of climate change which is increasingly affecting towns in coastal areas, including settlements in Semarang. Kemijen Urban Village is one of the informal settlements in Semarang, which has the highest intensity of flood that is 12 times during 5 years (2011-2015). The research question is how the level of local initiatives in flood disaster management in Kemijen, Semarang? This study aims to assess the level of local initiatives in Kemijen as the community adaptive capacity of flood prevention in pre-disaster, emergency response, and post-disaster. Local initiatives assessed on water supply, sanitation, food, shelter, health, drainage maintenance and waste management. This study shows the level of local initiatives in pre-disaster and post-disaster is almost same and bigger than the response phase. Scoring results showed that pre-disaster is 35.002, 27.9577 for emergency response, and post-disaster is 34.9862 with each category that is independent, empowered, and independent. This study also shows that local initiatives in Kemijen largely formed by individual initiative and only a few were formed by a collective initiative.

Governance of disaster risk reduction in Cameroon: The need to empower local government

Directory of Open Access Journals (Sweden)

Henry N. Bang

2013-02-01

Full Text Available The impact of natural hazards and/or disasters in Cameroon continues to hit local communities hardest, but local government lacks the ability to manage disaster risks adequately. This is partly due to the fact that the necessity to mainstream disaster risk reduction into local governance and development practices is not yet an underlying principle of Cameroon’s disaster management framework. Using empirical and secondary data, this paper analyses the governance of disaster risks in Cameroon with particular focus on the challenges local government faces in implementing disaster risk reduction strategies. The hypothesis is that the governance of disaster risks is too centralised at the national level, with huge implications for the effective governance of disaster risks at the local level. Although Cameroon has reinvigorated efforts to address growing disaster risks in a proactive way, it is argued that the practical actions are more reactive than proactive in nature. The overall aim is to explore the challenges and opportunities that local government has in the governance of disaster risks. Based on the findings from this research, policy recommendations are suggested on ways to mainstream disaster risk reduction strategies into local governance, and advance understanding and practice in the local governance of disaster risks in the country.

Risk factors for brain metastases after definitive chemoradiation for locally advanced non-small cell lung cancer

Directory of Open Access Journals (Sweden)

Petrović Marina

2009-01-01

Full Text Available Background/Aim. As therapy for locally advanced nonsmall cell lung carcinoma (NSCLC improves, brain metastases (BM still remain a great problem. The aim of the study was to analyze risk factors for BM in patients with locally advanced NSCLC after chemoradiation therapy. Methods. Records for 150 patients with non-resectable stage IIIA/IIIB NSCLC treated with combined chemoradiation therapy were analyzed. All of them had negative brain metastases imaging result before the treatment. Incidence of BM was examined in relation to age, sex, histological type, stage, performance status scale of wellbeing of cancer patients, weight loss, chemotherapy regimen and chemotherapy timing. Results. One- and 2-year incidence rates of BM were 19 and 31%, respectively. Among pretreatment parameters, stage IIIB was associated with a higher risk of BM (p < 0.004 vs stage IIIA. Histologically, the patients with nonsquamous tumors had an exceptionally high 2-year BM risk rate of 32% (p < 0.02. Examining treatment-related parameters, 1-year and 2-year actuarial risk of BM were 27 and 39%, respectively, in the patients receiving chemotherapy before radiotherapy and 15 and 20%, respectively, when radiotherapy was not delayed (p < 0.03. On multivariate analysis, timing of chemotherapy (p < 0.05 and stage IIIA vs IIIB (p < 0.01 remained statistically significant. Conclusion. Patients with IIIB stage, nonsquamous NSCLC, particularly those receiving sequential chemotherapy, had significantly high BM rates.

The role of metastasis-directed therapy and local therapy of the primary tumor in the management of oligometastatic prostate cancer.

Science.gov (United States)

Kim, Jongchan; Park, Jee Soo; Ham, Won Sik

2017-09-01

Oligometastasis has been proposed as an intermediate stage of cancer spread between localized disease and widespread metastasis. Oligometastatic malignancy is now being diagnosed more frequently as the result of improvements in diagnostic modalities such as functional imaging. The importance of oligometastasis in managing metastatic prostate cancer is that it is possible to treat with a curative aim by metastasis-directed or local therapy in selected patients. Many studies have shown that these aggressive treatments lead to improved survival in other oligometastatic malignancies. However, few studies have shown definitive benefits of metastasis-directed or local therapy in oligometastatic prostate cancer. Review of the available studies suggests that stereotactic radiotherapy (RT) of metastatic lesions in oligorecurrent disease is a feasible and safe modality for managing oligometastatic prostate cancer. Also, stereotactic RT can delay the start of androgen deprivation therapy. Many retrospective studies of metastatic prostate cancer have shown that patients undergoing local therapy seem to have superior overall and cancer-specific survival compared with patients not receiving local therapy. Ongoing prospective randomized trials would be helpful to evaluate the role of local therapy in oligometastatic prostate cancer.

The role of metastasis-directed therapy and local therapy of the primary tumor in the management of oligometastatic prostate cancer

Directory of Open Access Journals (Sweden)

Jongchan Kim

2017-09-01

Full Text Available Oligometastasis has been proposed as an intermediate stage of cancer spread between localized disease and widespread metas-tasis. Oligometastatic malignancy is now being diagnosed more frequently as the result of improvements in diagnostic modalities such as functional imaging. The importance of oligometastasis in managing metastatic prostate cancer is that it is possible to treat with a curative aim by metastasis-directed or local therapy in selected patients. Many studies have shown that these aggressive treatments lead to improved survival in other oligometastatic malignancies. However, few studies have shown definitive benefits of metastasis-directed or local therapy in oligometastatic prostate cancer. Review of the available studies suggests that stereotac-tic radiotherapy (RT of metastatic lesions in oligorecurrent disease is a feasible and safe modality for managing oligometastatic prostate cancer. Also, stereotactic RT can delay the start of androgen deprivation therapy. Many retrospective studies of metastatic prostate cancer have shown that patients undergoing local therapy seem to have superior overall and cancer-specific survival compared with patients not receiving local therapy. Ongoing prospective randomized trials would be helpful to evaluate the role of local therapy in oligometastatic prostate cancer.

Stereotactic Body Radiation Therapy for Locally Progressive and Recurrent Pancreatic Cancer after Prior Radiation

Directory of Open Access Journals (Sweden)

Philip Sutera

2018-03-01

Full Text Available IntroductionPancreatic adenocarcinoma is an aggressive malignancy that has consistently demonstrated poor outcomes despite aggressive treatments. Despite multimodal treatment, local disease progression and local recurrence are common. Management of recurrent or progressive pancreatic carcinomas proves a further challenge. In patients previously treated with radiation therapy, stereotactic body radiation therapy (SBRT is a promising modality capable of delivering high dose to the tumor while limiting dose to critical structures. We aimed to determine the feasibility and tolerability of SBRT for recurrent or local pancreatic cancer in patients previously treated with external beam radiation therapy (EBRT.Materials and methodsPatients treated with EBRT who developed recurrent or local pancreatic ductal adenocarcinoma treated with SBRT reirradiation at our institution, from 2004 to 2014 were reviewed. Our primary endpoints included overall survival (OS, local control, regional control, and late grade 3+ radiation toxicity. Endpoints were analyzed with the Kaplan–Meier method. The association of these survival endpoints with risk factors was studied with univariate Cox proportional hazards models.ResultsWe identified 38 patients with recurrent/progressive pancreatic cancer treated with SBRT following prior radiation therapy. Prior radiation was delivered to a median dose of 50.4 Gy in 28 fractions. SBRT was delivered to a median dose of 24.5 Gy in 1–3 fractions. Surgical resection was performed on 55.3% of all patients. Within a median follow-up of 24.4 months (inter-quartile range, 14.9–32.7 months, the median OS from diagnosis for the entire cohort was 26.6 months (95% CI: 20.3–29.8 with 2-year OS of 53.0%. Median survival from SBRT was 9.7 months (95% CI, 5.5–13.8. The 2-year freedom from local progression and regional progression was 58 and 82%, respectively. For the entire cohort, 18.4 and 10.5% experienced late grade 2

Nanoparticle-Based Brachytherapy Spacers for Delivery of Localized Combined Chemoradiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Kumar, Rajiv, E-mail: r.kumar@neu.edu [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States); Belz, Jodi [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Markovic, Stacey [Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts (United States); Jadhav, Tej; Fowle, William [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Niedre, Mark [Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts (United States); Cormack, Robert; Makrigiorgos, Mike G. [Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States); Sridhar, Srinivas [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States)

2015-02-01

Purpose: In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits. Methods and Materials: Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter, were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues. Results: The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days. Conclusions: The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when

Nanoparticle-Based Brachytherapy Spacers for Delivery of Localized Combined Chemoradiation Therapy

International Nuclear Information System (INIS)

Kumar, Rajiv; Belz, Jodi; Markovic, Stacey; Jadhav, Tej; Fowle, William; Niedre, Mark; Cormack, Robert; Makrigiorgos, Mike G.; Sridhar, Srinivas

2015-01-01

Purpose: In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits. Methods and Materials: Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter, were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues. Results: The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days. Conclusions: The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when

Comparative Risk Predictions of Second Cancers After Carbon-Ion Therapy Versus Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Eley, John G., E-mail: jeley@som.umaryland.edu [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Texas Graduate School of Biomedical Sciences, Houston, Texas (United States); Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland (United States); Friedrich, Thomas [GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt (Germany); Homann, Kenneth L.; Howell, Rebecca M. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Texas Graduate School of Biomedical Sciences, Houston, Texas (United States); Scholz, Michael; Durante, Marco [GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt (Germany); Newhauser, Wayne D. [Department of Physics and Astronomy, Louisiana State University and Agricultural and Mechanical College, Baton Rouge, Louisiana (United States); Mary Bird Perkins Cancer Center, Baton Rouge, Louisiana (United States)

2016-05-01

Purpose: This work proposes a theoretical framework that enables comparative risk predictions for second cancer incidence after particle beam therapy for different ion species for individual patients, accounting for differences in relative biological effectiveness (RBE) for the competing processes of tumor initiation and cell inactivation. Our working hypothesis was that use of carbon-ion therapy instead of proton therapy would show a difference in the predicted risk of second cancer incidence in the breast for a sample of Hodgkin lymphoma (HL) patients. Methods and Materials: We generated biologic treatment plans and calculated relative predicted risks of second cancer in the breast by using two proposed methods: a full model derived from the linear quadratic model and a simpler linear-no-threshold model. Results: For our reference calculation, we found the predicted risk of breast cancer incidence for carbon-ion plans-to-proton plan ratio, , to be 0.75 ± 0.07 but not significantly smaller than 1 (P=.180). Conclusions: Our findings suggest that second cancer risks are, on average, comparable between proton therapy and carbon-ion therapy.

The Early Result of Whole Pelvic Radiotherapy and Stereotactic Body Radiotherapy Boost for High Risk Localized Prostate Cancer

Directory of Open Access Journals (Sweden)

Yu-Wei eLin

2014-10-01

Full Text Available PurposeThe rationale for hypofractionated radiotherapy in the treatment of prostate cancer is based on the modern understanding of radiobiology and advances in stereotactic body radiotherapy (SBRT techniques. Whole-pelvis irradiation combined with SBRT boost for high-risk prostate cancer might escalate biologically effective dose without increasing toxicity. Here, we report our 4-year results of SBRT boost for high-risk localized prostate cancer.Methods and MaterialsFrom October 2009 to August 2012, 41 patients of newly diagnosed, high-risk or very high-risk (NCCN definition localized prostate cancer patients were treated with whole-pelvis irradiation and SBRT boost. The whole pelvis dose was 45Gy (25 fractions of 1.8Gy. The SBRT boost dose was 21 Gy (three fractions of 7 Gy. Ninety percent of these patients received hormone therapy. The toxicities of gastrointestinal (GI and genitourinary (GU tracts were scored by Common Toxicity Criteria Adverse Effect (CTCAE v3.0. Biochemical failure was defined by Phoenix definition.ResultsMedian follow-up was 42 months. Mean PSA before treatment was 44.18 ng/ml. Mean PSA level at 3, 6, 12, 18, and 24 months was 0.94, 0.44, 0.13, 0.12, and 0.05 ng/ml, respectively. The estimated 4-year biochemical failure-free survival was 91.9%. Three biochemical failures were observed. GI and GU tract toxicities were minimal. No grade 3 acute GU or GI toxicity was noted. During radiation therapy, 27% of the patient had grade 2 acute GU toxicity and 12% had grade 2 acute GI toxicity. At 3 months, most toxicity scores had returned to baseline. At the last follow up, there was no grade 3 late GU or GI toxicity.ConclusionsWhole-pelvis irradiation combined with SBRT boost for high-risk localized prostate cancer is feasible with minimal toxicity and encouraging biochemical failure-free survival. Continued accrual and follow-up would be necessary to confirm the biochemical control rate and the toxicity profiles.

National Trends and Predictors of Androgen Deprivation Therapy Use in Low-Risk Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Yang, David D. [Harvard Medical School, Boston, Massachusetts (United States); Muralidhar, Vinayak [Department of Medicine, Harvard Medical School, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Mahal, Brandon A. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Labe, Shelby A.; Nezolosky, Michelle D.; Vastola, Marie E.; King, Martin T.; Martin, Neil E.; Orio, Peter F. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Choueiri, Toni K. [Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Trinh, Quoc-Dien [Division of Urological Surgery, Harvard Medical School, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Spratt, Daniel E. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); University of Michigan, Ann Arbor, Michigan (United States); Hoffman, Karen E. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Feng, Felix Y. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); Departments of Urology & Medicine and Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California (United States); and others

2017-06-01

Purpose: Androgen deprivation therapy (ADT) is not recommended for low-risk prostate cancer because of its lack of benefit and potential for harm. We evaluated the incidence and predictors of ADT use in low-risk disease. Methods and Materials: Using the National Cancer Database, we identified 197,957 patients with low-risk prostate cancer (Gleason score of 3 + 3 = 6, prostate-specific antigen level <10 ng/mL, and cT1-T2a) diagnosed from 2004 to 2012 with complete demographic and treatment information. We used multiple logistic regression to evaluate predictors of ADT use and Cox regression to examine its association with all-cause mortality. Results: Overall ADT use decreased from 17.6% in 2004 to 3.5% in 2012. In 2012, 11.5% of low-risk brachytherapy patients and 7.6% of external beam radiation therapy patients received ADT. Among 82,352 irradiation-managed patients, predictors of ADT use included treatment in a community versus academic cancer program (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.50-1.71; P<.001; incidence, 14.0% vs 6.0% in 2012); treatment in the South (AOR, 1.51), Midwest (AOR, 1.81), or Northeast (AOR, 1.90) versus West (P<.001); and brachytherapy use versus external beam radiation therapy (AOR, 1.32; 95% CI, 1.27-1.37; P<.001). Among 25,196 patients who did not receive local therapy, predictors of primary ADT use included a Charlson-Deyo comorbidity score of ≥2 versus 0 (AOR, 1.42; 95% CI, 1.06-1.91; P=.018); treatment in a community versus academic cancer program (AOR, 1.61; 95% CI, 1.37-1.90; P<.001); and treatment in the South (AOR, 1.26), Midwest (AOR, 1.52), or Northeast (AOR, 1.28) versus West (P≤.008). Primary ADT use was associated with increased all-cause mortality in patients who did not receive local therapy (adjusted hazard ratio, 1.28; 95% CI, 1.14-1.43; P<.001) after adjustment for age and comorbidity. Conclusions: ADT use in low-risk prostate cancer has declined nationally but may remain an issue

Clinical results of proton beam therapy for skull base chordoma

International Nuclear Information System (INIS)

Igaki, Hiroshi; Tokuuye, Koichi; Okumura, Toshiyuki; Sugahara, Shinji; Kagei, Kenji; Hata, Masaharu; Ohara, Kiyoshi; Hashimoto, Takayuki; Tsuboi, Koji; Takano, Shingo; Matsumura, Akira; Akine, Yasuyuki

2004-01-01

Purpose: To evaluate clinical results of proton beam therapy for patients with skull base chordoma. Methods and materials: Thirteen patients with skull base chordoma who were treated with proton beams with or without X-rays at the University of Tsukuba between 1989 and 2000 were retrospectively reviewed. A median total tumor dose of 72.0 Gy (range, 63.0-95.0 Gy) was delivered. The patients were followed for a median period of 69.3 months (range, 14.6-123.4 months). Results: The 5-year local control rate was 46.0%. Cause-specific, overall, and disease-free survival rates at 5 years were 72.2%, 66.7%, and 42.2%, respectively. The local control rate was higher, without statistical significance, for those with preoperative tumors <30 mL. Partial or subtotal tumor removal did not yield better local control rates than for patients who underwent biopsy only as the latest surgery. Conclusion: Proton beam therapy is effective for patients with skull base chordoma, especially for those with small tumors. For a patient with a tumor of <30 mL with no prior treatment, biopsy without tumor removal seems to be appropriate before proton beam therapy

What is the optimal management of high risk, clinically localized prostate cancer?

Science.gov (United States)

Eastham, James A; Evans, Christopher P; Zietman, Anthony

2010-01-01

To summarize the presentations and debate regarding the optimal treatment of localized high-risk prostate cancer as presented at the 2009 Spring Meeting of the Society of Urologic Oncology. The debate was centered on presentations arguing for radical prostatectomy (RP) or radiotherapy as the optimal treatment for this condition. The meeting presentations are summarized by their respective presenters herein. Dr. James Eastham presents the varied definitions for "high-risk" prostate cancer as strongly influencing which patients end up in this cohort. Based upon this, between 3% and 38% of patients with high-risk features could be defined as "high-risk". Despite that, these men do not have a uniformly poor prognosis after RP, and attention to surgical principles as outlined improve outcomes. Disease-specific survival at 12 years is excellent and up to one-half of these men may not need adjuvant or salvage therapies, depending on their specific disease characteristics. Adjuvant or salvage radiotherapies improve outcomes and are part of a sequential approach to treating these patients. Dr. Anthony Zietman presented radiotherapy as the gold-standard based upon large, randomized clinical trials of intermediate- and high-risk prostate cancer patients. Compared with androgen deprivation alone, the addition of radiotherapy provided a 12% cancer-specific survival advantage and 10% overall survival advantage. Dose escalation seems to confer further improvements in cancer control without significant escalation of toxicities, with more data forthcoming. There are no randomized trials comparing RP to radiotherapy for any risk category. In high-risk prostate cancer patients, both approaches have potential benefits and cumulative toxicities that must be matched to disease characteristics and patient expectations in selecting a treatment course. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Current trends in local antibacterial therapy of periprosthetic infection and osteomyelitis

Directory of Open Access Journals (Sweden)

S. A. Bozhkova

2015-01-01

Full Text Available The rational use of antibiotics in the treatment of orthopedic infection still presents a significant problem. Local antibiotic delivery systems enable to achieve effective concentrations of drugs in the focus of bone infection without the development of toxicity. It is the important accompaniment to systemic antibiotics in the treatment of periprosthetic infection and osteomyelitis. The data collected through the PubMed and eLIBRARY databases (http://www.ncbi.nlm. nih.gov/pubmed, 1995-2015; http://elibrary.ru, 2005-2015 years present the information about bone substitutes used for local antibiotic therapy in scientific investigations and in clinical practice. The information is submitted in accordance with the groups of materials: cements based on polymethylmethacrylate, bone grafts, demineralized bone matrix, bioceramics, natural and synthetic polymers, combined antibiotic delivery systems. The majority of these materials have only been studied experimentally and only a limited range of them is registered for use in clinical practice. Informing orthopedic surgeons about current methods of local antibiotic use is the key to the development of a modern integrated approach to the therapy of infectious complications after orthopedic surgery.

Adjuvant neutron therapy in complex treatment of patients with locally advanced breast cancer

Science.gov (United States)

Lisin, V. A.; Velikaya, V. V.; Startseva, Zh. A.; Popova, N. O.; Goldberg, V. E.

2017-09-01

The study included 128 patients with stage T2-4N0-3M0 locally advanced breast cancer. All patients were divided into two groups. Group I (study group) consisted of 68 patients, who received neutron therapy, and group II (control group) comprised 60 patients, who received electron beam therapy. Neutron therapy was well tolerated by the patients and 1-2 grade radiation skin reactions were the most common. Neutron therapy was shown to be effective in multimodality treatment of the patients with locally advanced breast cancer. The 8-year recurrence-free survival rate in the patients with locally advanced breast cancer was 94.5 ± 4.1% after neutron therapy and 81.4 ± 5.9% after electron beam therapy (p = 0.05).

Generalized Fragility Relationships with Local Site Conditions for Probabilistic Performance-based Seismic Risk Assessment of Bridge Inventories

Directory of Open Access Journals (Sweden)

Sivathayalan S.

2012-01-01

Full Text Available The current practice of detailed seismic risk assessment cannot be easily applied to all the bridges in a large transportation networks due to limited resources. This paper presents a new approach for seismic risk assessment of large bridge inventories in a city or national bridge network based on the framework of probabilistic performance based seismic risk assessment. To account for the influences of local site effects, a procedure to generate site-specific hazard curves that includes seismic hazard microzonation information has been developed for seismic risk assessment of bridge inventories. Simulated ground motions compatible with the site specific seismic hazard are used as input excitations in nonlinear time history analysis of representative bridges for calibration. A normalizing procedure to obtain generalized fragility relationships in terms of structural characteristic parameters of bridge span and size and longitudinal and transverse reinforcement ratios is presented. The seismic risk of bridges in a large inventory can then be easily evaluated using the normalized fragility relationships without the requirement of carrying out detailed nonlinear time history analysis.

Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids

Science.gov (United States)

2008-08-01

SUBJECT TERMS Cancer therapy by localized immune response, Magneto -rehological Fluids 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT...Metastasized Breast Cancer by Localized Therapy utilizing Biocompatible Magnetic Fluids PRINCIPAL INVESTIGATOR: Cahit Evrensel...2008 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy utilizing

Risk-optimized proton therapy to minimize radiogenic second cancers

Science.gov (United States)

Rechner, Laura A.; Eley, John G.; Howell, Rebecca M.; Zhang, Rui; Mirkovic, Dragan; Newhauser, Wayne D.

2015-01-01

Proton therapy confers substantially lower predicted risk of second cancer compared with photon therapy. However, no previous studies have used an algorithmic approach to optimize beam angle or fluence-modulation for proton therapy to minimize those risks. The objectives of this study were to demonstrate the feasibility of risk-optimized proton therapy and to determine the combination of beam angles and fluence weights that minimize the risk of second cancer in the bladder and rectum for a prostate cancer patient. We used 6 risk models to predict excess relative risk of second cancer. Treatment planning utilized a combination of a commercial treatment planning system and an in-house risk-optimization algorithm. When normal-tissue dose constraints were incorporated in treatment planning, the risk model that incorporated the effects of fractionation, initiation, inactivation, and repopulation selected a combination of anterior and lateral beams, which lowered the relative risk by 21% for the bladder and 30% for the rectum compared to the lateral-opposed beam arrangement. Other results were found for other risk models. PMID:25919133

A Novel Risk Stratification to Predict Local-Regional Failures in Urothelial Carcinoma of the Bladder After Radical Cystectomy

Energy Technology Data Exchange (ETDEWEB)

Baumann, Brian C. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Guzzo, Thomas J. [Department of Urology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); He Jiwei [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Keefe, Stephen M. [Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Tucker, Kai; Bekelman, Justin E. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Hwang, Wei-Ting [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vaughn, David J. [Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Malkowicz, S. Bruce [Department of Urology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Christodouleas, John P., E-mail: christojo@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

2013-01-01

in cases of locally advanced disease and provides a rubric based on pathological stage and number of nodes removed that stratifies patients into 3 groups with significantly different LF risks to simplify patient selection for future adjuvant radiation therapy trials.

A Novel Risk Stratification to Predict Local-Regional Failures in Urothelial Carcinoma of the Bladder After Radical Cystectomy

International Nuclear Information System (INIS)

Baumann, Brian C.; Guzzo, Thomas J.; He Jiwei; Keefe, Stephen M.; Tucker, Kai; Bekelman, Justin E.; Hwang, Wei-Ting; Vaughn, David J.; Malkowicz, S. Bruce; Christodouleas, John P.

2013-01-01

cases of locally advanced disease and provides a rubric based on pathological stage and number of nodes removed that stratifies patients into 3 groups with significantly different LF risks to simplify patient selection for future adjuvant radiation therapy trials.

Outcome According to Elective Pelvic Radiation Therapy in Patients With High-Risk Localized Prostate Cancer: A Secondary Analysis of the GETUG 12 Phase 3 Randomized Trial

Energy Technology Data Exchange (ETDEWEB)

Blanchard, Pierre, E-mail: pierre.blanchard@gustaveroussy.fr [Radiation Oncology, Gustave Roussy Cancer Center, Villejuif (France); University of Paris-Sud, Cancer Campus, Villejuif (France); Faivre, Laura [Biostatistics, Gustave Roussy Cancer Center, Villejuif (France); Lesaunier, François [Radiation Oncology, Centre Francois Baclesse, Caen (France); Salem, Naji [Radiation Oncology, Institut Paoli Calmette, Marseille (France); Mesgouez-Nebout, Nathalie [Radiation Oncology, Institut de Cancérologie de l' Ouest, Angers (France); Deniau-Alexandre, Elisabeth [Centre Hospitalier La Roche sur Yon, La Roche sur Yon (France); Rolland, Frédéric [Medical Oncology, Institut de Cancérologie de l' Ouest, Nantes (France); Ferrero, Jean-Marc [Medical Oncology, Centre Antoine Lacassagne, Nice (France); Houédé, Nadine [Medical Oncology, Institut Bergonié, Bordeaux (France); Mourey, Loïc [Institut Claudius Regaud, Toulouse (France); Théodore, Christine [Hospital Foch, Suresnes (France); Krakowski, Ivan [Centre Alexis Vautrin, Vandoeuvre-lès-Nancy (France); Berdah, Jean-François [Clinique Sainte Marguerite, Hyeres (France); Baciuchka, Marjorie [Centre Hospitalier de la Timone, Marseille (France); Laguerre, Brigitte [Centre Eugène Marquis, Rennes (France); Davin, Jean-Louis [Clinique Sainte Catherine, Avignon (France); Habibian, Muriel [R& D UNICANCER, Paris (France); UNICANCER, Paris (France); Culine, Stéphane [Department of Medical Oncology, Hopital Saint-Louis, APHP, Paris (France); and others

2016-01-01

Purpose: The role of pelvic elective nodal irradiation (ENI) in the management of prostate cancer is controversial. This study analyzed the role of pelvic radiation therapy (RT) on the outcome in high-risk localized prostate cancer patients included in the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG) 12 trial. Methods and Materials: Patients with a nonpretreated high-risk localized prostate cancer and a staging lymphadenectomy were randomly assigned to receive either goserelin every 3 months for 3 years and 4 cycles of docetaxel plus estramustine or goserelin alone. Local therapy was administered 3 months after the start of systemic treatment. Performance of pelvic ENI was left to the treating physician. Only patients treated with primary RT were included in this analysis. The primary endpoint was biochemical progression-free survival (bPFS). Results: A total of 413 patients treated from 2002 to 2006 were included, of whom 358 were treated using primary RT. A total of 208 patients received pelvic RT and 150 prostate-only RT. Prostate-specific antigen (PSA) concentration, Gleason score, or T stage did not differ according to performance of pelvic RT; pN+ patients more frequently received pelvic RT than pN0 patients (P<.0001). Median follow-up was 8.8 years. In multivariate analysis, bPFS was negatively impacted by pN stage (hazard ratio [HR]: 2.52 [95% confidence interval [CI]: 1.78-3.54], P<.0001), Gleason score 8 or higher (HR: 1.41 [95% CI: 1.03-1.93], P=.033) and PSA higher than 20 ng/mL (HR: 1.41 [95% CI: 1.02-1.96], P=.038), and positively impacted by the use of chemotherapy (HR: 0.66 [95% CI: 0.48-0.9], P=.009). There was no association between bPFS and use of pelvic ENI in multivariate analysis (HR: 1.10 [95% CI: 0.78-1.55], P=.60), even when analysis was restricted to pN0 patients (HR: 0.88 [95% CI: 0.59-1.31], P=.53). Pelvic ENI was not associated with increased acute or late patient reported toxicity. Conclusions: This unplanned analysis of

Postmenopausal vaginal atrophy: evaluation of treatment with local estrogen therapy

Directory of Open Access Journals (Sweden)

Minkin MJ

2014-03-01

Full Text Available Mary Jane Minkin,1 Ricardo Maamari,2 Suzanne Reiter3 1Department of Gynecology and Reproductive Medicine, Yale University School of Medicine, New Haven, CT, USA; 2Novo Nordisk Inc., Plainsboro, NJ, USA; 3Mid-County Health Center, Largo, FL, USA Abstract: Postmenopausal vaginal atrophy, resulting from decreased estrogen production, frequently requires treatment. Estrogen preparations provide the most effective treatment; local application is preferred to systemic drugs when treating only vaginal symptoms. As local estrogen therapies have comparable efficacy, this study aimed to understand treatment practices, assess experiences with different forms of local estrogen-delivering applicators, and evaluate satisfaction. Women who were US residents aged ≥18 years, menopausal (no spontaneous menstrual period for ≥1 year or with a double oophorectomy, and receiving local estrogen therapy for 1–6 months (vaginal cream [supplied with a reusable applicator] or vaginal tablets [supplied with a single-use/disposable applicator], completed an online questionnaire. Data from 200 women (100 cream users and 100 tablet users; mean therapy duration 3.48 months showed that most stored medication in the room in which it was applied (88% and applied it at bedtime (71%, a procedure for which cream users required, on average, more than twice the time of tablet users (5.08 minutes versus 2.48 minutes. Many cream users applied larger-than-prescribed amounts of cream, attempting to achieve greater efficacy (42%, or lower-than-recommended doses (45%, most frequently to avoid messiness (33% or leakage (30%. More tablet users (69% than cream users (14% were "extremely satisfied" with their applicator. Postmenopausal women using local estrogen therapy were generally more satisfied with the application of vaginal tablets than cream. Patient satisfaction may help to facilitate accurate dosing. Positive perceptions of medication will help to optimize treatment, which

Risk analysis of external radiation therapy

International Nuclear Information System (INIS)

Arvidsson, Marcus

2011-09-01

External radiation therapy is carried out via a complex treatment process in which many different groups of staff work together. Much of the work is dependent on and in collaboration with advanced technical equipment. The purpose of the research task has been to identify a process for external radiation therapy and to identify, test and analyze a suitable method for performing risk analysis of external radiation therapy

Refining Preoperative Therapy for Locally Advanced Rectal Cancer

Science.gov (United States)

In the PROSPECT trial, patients with locally advanced, resectable rectal cancer will be randomly assigned to receive either standard neoadjuvant chemoradiation therapy or neoadjuvant FOLFOX chemotherapy, with chemoradiation reserved for nonresponders.

Effect of Family Oriented Early Intervention Based on Localized Play Therapy on the Clinical Symptoms of Preschool Children with ADHD

Directory of Open Access Journals (Sweden)

سعید رحیمی پردنجانی

2016-06-01

Full Text Available Current study was aimed to investigate the effect of localized play therapy on reducing symptoms of attention deficiency and hyper activity/impulsivity in preschool children with ADHD. The method of this study was an applied semi-experimental study designed as pretest-posttest with control group. Twenty four mothers with ADHD children were selected through multi-stage sampling and randomly arranged in experimental or control groups. The experimental group participated in a 10 sessions Localized Play Therapy (LPT intervention program, while the control group was on the waiting list. Assessment tools were the Vanderbilt ADHD Teacher Rating Scale (Wolraich, et al., 1997 and a semiorganized clinical interview. Data were analyzed by using a repeated measure analysis of variance. The results showed that there were  significant differences between the control and experimental groups in attention deficiency and hyper activity/impulsivity scores of pre-test and post-test. In conclusion, it can be indicated that family oriented early intervention based on LPT is effective in reducing clinical symptoms of preschool children with ADHD. Therefore, this method can be considered as an effective therapeutic method for ADHD children by experts and parents

Adjuvant VHF therapy in locally recurrent and primary unresectable rectal cancer

International Nuclear Information System (INIS)

Trotter, J.M.; Lamb, M.H.; Bayliss, E.J.; Edis, A.J.; Blackwell, J.B.; Shepherd, J.M.; Cassidy, B.

1996-01-01

In a prospective randomized study, 434 MHz microwave therapy combined with external beam radiotherapy (VHF+RT) was compared with standard external beam radiotherapy (RT) in controlling locally recurrent or unresectable primary adenocarcinoma of the rectum. Independent assessors documented quality of life scores, performance status, toxicities local response to treatment, and systemic disease progression before treatment and after treatment and every 8 week thereafter. Of 75 patients randomized, 73 were eligible for inclusion in the study. Forty-three of these patients had local pelvic tumour recurrence only and 21 also had distant metastases. In addition, nine patients had primary inoperable carcinomas, two of whom also had metastases. Thirty-seven patients were randomized to RT and 36 to VHF+RT. Th median dose of radiation in the VHF+RT arm was 4275 cGy with a median fraction size of 150 cGy and median duration of therapy of 48.5 days versus 4500 cGy in the RT-only arm with a median fraction size of 180 cGy and median duration of therapy of 38 days. These doses are unlikely to be significantly different in biological effect. No significant difference between the two groups was observed in extent and duration of local control, measures of toxicity or quality of life scores. Additionally, survival and cumulative incidence of pelvic site of first progression did not differ significantly between the groups. It is concluded that VHF microwave therapy in conjunction with radiotherapy produces no therapeutic advantage over conventional radiation therapy alone in the treatment of locally recurrent rectal carcinoma. 35 refs., 8 tabs., 3 figs

Survival After Conservative Management Versus External Beam Radiation Therapy in Elderly Patients With Localized Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Dell' Oglio, Paolo, E-mail: paolo.delloglio@gmail.com [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Québec (Canada); Department of Urology and Division of Experimental Oncology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan (Italy); Boehm, Katharina [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Québec (Canada); Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg (Germany); Trudeau, Vincent [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Québec (Canada); Department of Urology, University of Montreal Health Center, Montreal, Québec (Canada); Tian, Zhe [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Québec (Canada); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec (Canada); Larcher, Alessandro [Department of Urology and Division of Experimental Oncology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan (Italy); Leyh-Bannurah, Sami-Ramzi [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Québec (Canada); Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg (Germany); Moschini, Marco; Capitanio, Umberto [Department of Urology and Division of Experimental Oncology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan (Italy); Shariat, Shahrokh F. [Department of Urology, Medical University of Vienna and General Hospital, Vienna (Austria); and others

2016-12-01

Purpose: To compare survival in elderly men with clinically localized prostate cancer (PCa) according to treatment type, defined as radiation therapy (RT) with or without androgen deprivation therapy (ADT) versus conservative management (observation). Methods and Materials: In the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database, we identified 23,790 patients aged 80 years or more with clinically localized PCa treated with either RT or observation between 1991 and 2009. Competing risks analyses focused on cancer-specific mortality and other-cause mortality, after accounting for confounders. All analyses were repeated after stratification according to grade (well-differentiated vs moderately differentiated vs poorly differentiated disease), race, and United States region, in patients with no comorbidities and in patients with at least 1 comorbidity. Analyses were repeated within most contemporary patients, namely those treated between 2001 and 2009. Results: Radiation therapy was associated with more favorable cancer-specific mortality rates than observation in patients with moderately differentiated disease (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.66-0.94; P=.009) and in patients with poorly differentiated disease (HR 0.58; 95% CI 0.49-0.69; P<.001). Conversely, the benefit of RT was not observed in well-differentiated disease. The benefit of RT was confirmed in black men (HR 0.54; 95% CI 0.35-0.83; P=.004), across all United States regions (all P≤.004), in the subgroups of the healthiest patients (HR 0.67; 95% CI 0.57-0.78; P<.001), in patients with at least 1 comorbidity (HR 0.69; 95% CI 0.56-0.83; P<.001), and in most contemporary patients (HR 0.55; 95% CI 0.46-0.66; P<.001). Conclusions: Radiation therapy seems to be associated with a reduction in the risk of death from PCa relative to observation in elderly patients with clinically localized PCa, except for those with well-differentiated disease.

Survival After Conservative Management Versus External Beam Radiation Therapy in Elderly Patients With Localized Prostate Cancer

International Nuclear Information System (INIS)

Dell'Oglio, Paolo; Boehm, Katharina; Trudeau, Vincent; Tian, Zhe; Larcher, Alessandro; Leyh-Bannurah, Sami-Ramzi; Moschini, Marco; Capitanio, Umberto; Shariat, Shahrokh F.

2016-01-01

Purpose: To compare survival in elderly men with clinically localized prostate cancer (PCa) according to treatment type, defined as radiation therapy (RT) with or without androgen deprivation therapy (ADT) versus conservative management (observation). Methods and Materials: In the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database, we identified 23,790 patients aged 80 years or more with clinically localized PCa treated with either RT or observation between 1991 and 2009. Competing risks analyses focused on cancer-specific mortality and other-cause mortality, after accounting for confounders. All analyses were repeated after stratification according to grade (well-differentiated vs moderately differentiated vs poorly differentiated disease), race, and United States region, in patients with no comorbidities and in patients with at least 1 comorbidity. Analyses were repeated within most contemporary patients, namely those treated between 2001 and 2009. Results: Radiation therapy was associated with more favorable cancer-specific mortality rates than observation in patients with moderately differentiated disease (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.66-0.94; P=.009) and in patients with poorly differentiated disease (HR 0.58; 95% CI 0.49-0.69; P<.001). Conversely, the benefit of RT was not observed in well-differentiated disease. The benefit of RT was confirmed in black men (HR 0.54; 95% CI 0.35-0.83; P=.004), across all United States regions (all P≤.004), in the subgroups of the healthiest patients (HR 0.67; 95% CI 0.57-0.78; P<.001), in patients with at least 1 comorbidity (HR 0.69; 95% CI 0.56-0.83; P<.001), and in most contemporary patients (HR 0.55; 95% CI 0.46-0.66; P<.001). Conclusions: Radiation therapy seems to be associated with a reduction in the risk of death from PCa relative to observation in elderly patients with clinically localized PCa, except for those with well-differentiated disease.

Stroke After Radiation Therapy for Head and Neck Cancer: What Is the Risk?

Energy Technology Data Exchange (ETDEWEB)

Arthurs, Erin [Department of Public Health Sciences, Queen' s University, Kingston, Ontario (Canada); Hanna, Timothy P. [Division of Cancer Care and Epidemiology, Queen' s University, Kingston, Ontario (Canada); Department of Oncology, Queen' s University, Kingston, Ontario (Canada); Zaza, Khaled [Department of Oncology, Queen' s University, Kingston, Ontario (Canada); Peng, Yingwei [Department of Public Health Sciences, Queen' s University, Kingston, Ontario (Canada); Hall, Stephen F., E-mail: sfh@queensu.ca [Division of Cancer Care and Epidemiology, Queen' s University, Kingston, Ontario (Canada); Department of Otolaryngology, Queen' s University, Kingston, Ontario (Canada)

2016-11-01

Purpose: A retrospective population-based cohort study was conducted to determine the risk of ischemic stroke with respect to time, associated with curative radiation therapy in head and neck squamous cell carcinomas (HNSCC). Methods and Materials: On the basis of data from the Ontario Cancer Registry and regional cancer treatment centers, 14,069 patients were identified with diagnoses of squamous cell carcinoma of the oral cavity, larynx, and pharynx who were treated for cure between 1990 and 2010. Hazards of stroke and time to stroke were examined, accounting for the competing risk of death. Stroke risk factors identified through diagnostic and procedural administrative codes were adjusted for in the comparison between treatment regimens, which included surgery alone versus radiation therapy alone and surgery alone versus any exposure to radiation therapy. Results: Overall, 6% of patients experienced an ischemic stroke after treatment, with 5% experiencing a stroke after surgery, 8% after radiation therapy alone, and 6% after any exposure to radiation therapy. The cause-specific hazard ratios of ischemic stroke after radiation therapy alone and after any exposure to radiation therapy compared with surgery were 1.70 (95% confidence interval [CI]: 1.41-2.05) and 1.46 (95% CI: 1.23-1.73), respectively, after adjustment for stroke risk factors, patient factors, and disease-related factors. Conclusions: Radiation therapy was associated with an increased risk of ischemic stroke compared with surgery alone: for both radiation therapy alone and after all treatment modalities that included any radiation treatment were combined. Because of a shift toward a younger HNSCC patient population, our results speak to the need for adequate follow-up and survivorship care among patients who have been treated with radiation therapy. Advances in treatment that minimize chronic morbidity also require further evaluation.

Volumetric modulated arc therapy for lung stereotactic radiation therapy can achieve high local control rates.

Science.gov (United States)

Yamashita, Hideomi; Haga, Akihiro; Takahashi, Wataru; Takenaka, Ryousuke; Imae, Toshikazu; Takenaka, Shigeharu; Nakagawa, Keiichi

2014-11-11

The aim of this study was to report the outcome of primary or metastatic lung cancer patients undergoing volumetric modulated arc therapy for stereotactic body radiation therapy (VMAT-SBRT). From October 2010 to December 2013, consecutive 67 lung cancer patients received single-arc VMAT-SBRT using an Elekta-synergy system. All patients were treated with an abdominal compressor. The gross tumor volumes were contoured on 10 respiratory phases computed tomography (CT) datasets from 4-dimensional (4D) CT and merged into internal target volumes (ITVs). The planning target volume (PTV) margin was isotropically taken as 5 mm. Treatment was performed with a D95 prescription of 50 Gy (43 cases) or 55 Gy (12 cases) in 4 fractions for peripheral tumor or 56 Gy in 7 fractions (12 cases) for central tumor. Among the 67 patients, the median age was 73 years (range, 59-95 years). Of the patients, male was 72% and female 28%. The median Karnofsky performance status was 90-100% in 39 cases (58%) and 80-90% in 20 cases (30%). The median follow-up was 267 days (range, 40-1162 days). Tissue diagnosis was performed in 41 patients (61%). There were T1 primary lung tumor in 42 patients (T1a in 28 patients, T1b in 14 patients), T2 in 6 patients, three T3 in 3 patients, and metastatic lung tumor in 16 patients. The median mean lung dose was 6.87 Gy (range, 2.5-15 Gy). Six patients (9%) developed radiation pneumonitis required by steroid administration. Actuarial local control rate were 100% and 100% at 1 year, 92% and 75% at 2 years, and 92% and 75% at 3 years in primary and metastatic lung cancer, respectively (p =0.59). Overall survival rate was 83% and 84% at 1 year, 76% and 53% at 2 years, and 46% and 20% at 3 years in primary and metastatic lung cancer, respectively (p =0.12). Use of VMAT-based delivery of SBRT in primary in metastatic lung tumors demonstrates high local control rates and low risk of normal tissue complications.

Volumetric modulated arc therapy for lung stereotactic radiation therapy can achieve high local control rates

International Nuclear Information System (INIS)

Yamashita, Hideomi; Haga, Akihiro; Takahashi, Wataru; Takenaka, Ryousuke; Imae, Toshikazu; Takenaka, Shigeharu; Nakagawa, Keiichi

2014-01-01

The aim of this study was to report the outcome of primary or metastatic lung cancer patients undergoing volumetric modulated arc therapy for stereotactic body radiation therapy (VMAT-SBRT). From October 2010 to December 2013, consecutive 67 lung cancer patients received single-arc VMAT-SBRT using an Elekta-synergy system. All patients were treated with an abdominal compressor. The gross tumor volumes were contoured on 10 respiratory phases computed tomography (CT) datasets from 4-dimensional (4D) CT and merged into internal target volumes (ITVs). The planning target volume (PTV) margin was isotropically taken as 5 mm. Treatment was performed with a D95 prescription of 50 Gy (43 cases) or 55 Gy (12 cases) in 4 fractions for peripheral tumor or 56 Gy in 7 fractions (12 cases) for central tumor. Among the 67 patients, the median age was 73 years (range, 59–95 years). Of the patients, male was 72% and female 28%. The median Karnofsky performance status was 90-100% in 39 cases (58%) and 80-90% in 20 cases (30%). The median follow-up was 267 days (range, 40–1162 days). Tissue diagnosis was performed in 41 patients (61%). There were T1 primary lung tumor in 42 patients (T1a in 28 patients, T1b in 14 patients), T2 in 6 patients, three T3 in 3 patients, and metastatic lung tumor in 16 patients. The median mean lung dose was 6.87 Gy (range, 2.5-15 Gy). Six patients (9%) developed radiation pneumonitis required by steroid administration. Actuarial local control rate were 100% and 100% at 1 year, 92% and 75% at 2 years, and 92% and 75% at 3 years in primary and metastatic lung cancer, respectively (p = 0.59). Overall survival rate was 83% and 84% at 1 year, 76% and 53% at 2 years, and 46% and 20% at 3 years in primary and metastatic lung cancer, respectively (p = 0.12). Use of VMAT-based delivery of SBRT in primary in metastatic lung tumors demonstrates high local control rates and low risk of normal tissue complications

Post-operative radiation therapy for locally advanced hypopharyngeal carcinoma

International Nuclear Information System (INIS)

Nishimura, Hideki; Sasaki, Ryohei; Yoshida, Takeshi

2011-01-01

We retrospectively analyzed the treatment outcomes of post-operative radiation therapy (PORT) after radical surgery for locally advanced hypopharyngeal carcinoma. From August 2000 to July 2009, 62 patients with hypopharyngeal squamous cell carcinoma were treated with radical surgery followed by PORT in our institute. All patients were followed up for more than 6 months or until any events. All patients underwent a total laryngectomy and neck node dissection prior to PORT. There were 55 male and 7 female patients, with ages ranging from 45 to 82 years (median: 64). Pathologic stage was IVA in 55 and IVB in 7 patients. Irradiation dose ranged from 46 to 70 Gy (median: 60). Twenty-four patients received concurrent chemotherapy. The median follow-up period for surviving patients was 43 months. The 3-year overall and relapse-free survival rates were 56% and 51%, respectively. There was 1 patient with local recurrence and 9 patients with neck node recurrence, and the 3-year loco-regional control rate was 85%. There were 16 patients with distant metastases and the 3-year freedom form distant metastasis rate was 71%. Patients with extra nodal invasion (ENI) had a statistically poorer prognosis (p=0.008). The incidence rate of loco-regional recurrence and distant metastasis were statistically higher in the patients with ENI (p=0.017 and p=0.009, respectively). PORT with concurrent chemotherapy is deemed to be a standard treatment for such high-risk patients. Conformal and precise radiation treatment such as IMRT might also be considered for such high-risk patients in the near future. (author)

Daily Aspirin Therapy: Understand the Benefits and Risks

Science.gov (United States)

Daily aspirin therapy: Understand the benefits and risks Daily aspirin therapy can be a lifesaving option, but it's not ... everyone. Get the facts before considering a daily aspirin. By Mayo Clinic Staff Daily aspirin therapy may ...

External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

International Nuclear Information System (INIS)

Cho, Eunpi; Mostaghel, Elahe A.; Russell, Kenneth J.; Liao, Jay J.; Konodi, Mark A.; Kurland, Brenda F.; Marck, Brett T.; Matsumoto, Alvin M.; Dalkin, Bruce L.; Montgomery, R. Bruce

2015-01-01

Purpose: Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. Methods and Materials: A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Results: A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse. Conclusions: Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression

External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

Energy Technology Data Exchange (ETDEWEB)

Cho, Eunpi [University of Washington School of Medicine, Seattle, Washington (United States); Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Mostaghel, Elahe A. [Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Russell, Kenneth J.; Liao, Jay J.; Konodi, Mark A. [University of Washington School of Medicine, Seattle, Washington (United States); Kurland, Brenda F. [University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Marck, Brett T. [Veterans Affairs Puget Sound Health Care System, Seattle, Washington (United States); Matsumoto, Alvin M. [University of Washington School of Medicine, Seattle, Washington (United States); Veterans Affairs Puget Sound Health Care System, Seattle, Washington (United States); Dalkin, Bruce L. [University of Washington School of Medicine, Seattle, Washington (United States); Montgomery, R. Bruce, E-mail: rbmontgo@uw.edu [University of Washington School of Medicine, Seattle, Washington (United States)

2015-06-01

Purpose: Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. Methods and Materials: A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Results: A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse. Conclusions: Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression

Treatment of Locally Advanced Pancreatic Cancer: The Role of Radiation Therapy

International Nuclear Information System (INIS)

Johung, Kimberly; Saif, Muhammad Wasif; Chang, Bryan W.

2012-01-01

Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy.

Protocol-based image-guided salvage brachytherapy. Early results in patients with local failure of prostate cancer after radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Lahmer, G.; Lotter, M.; Kreppner, S.; Fietkau, R.; Strnad, V. [University Hospital Erlangen (Germany). Dept. of Radiation Oncology

2013-08-15

Purpose: To assess the overall clinical outcome of protocol-based image-guided salvage pulsed-dose-rate brachytherapy for locally recurrent prostate cancer after radiotherapy failure particularly regarding feasibility and side effects. Patients and methods: Eighteen consecutive patients with locally recurrent prostate cancer (median age, 69 years) were treated during 2005-2011 with interstitial PDR brachytherapy (PDR-BT) as salvage brachytherapy after radiotherapy failure. The treatment schedule was PDR-BT two times with 30 Gy (pulse dose 0.6 Gy/h, 24 h per day) corresponding to a total dose of 60 Gy. Dose volume adaptation was performed with the aim of optimal coverage of the whole prostate (V{sub 100} > 95 %) simultaneously respecting the protocol-based dose volume constraints for the urethra (D{sub 0.1} {sub cc} < 130 %) and the rectum (D{sub 2} {sub cc} < 50-60 %) taking into account the previous radiation therapy. Local relapse after radiotherapy (external beam irradiation, brachytherapy with J-125 seeds or combination) was confirmed mostly via choline-PET and increased PSA levels. The primary endpoint was treatment-related late toxicities - particularly proctitis, anal incontinence, cystitis, urinary incontinence, urinary frequency/urgency, and urinary retention according to the Common Toxicity Criteria. The secondary endpoint was PSA-recurrence-free survival. Results: We registered urinary toxicities only. Grade 2 and grade 3 toxicities were observed in up to 11.1 % (2/18) and 16.7 % (3/18) of patients, respectively. The most frequent late-event grade 3 toxicity was urinary retention in 17 % (3/18) of patients. No late gastrointestinal side effects occurred. The biochemical PSA-recurrence-free survival probability at 3 years was 57.1 %. The overall survival at 3 years was 88.9 %; 22 % (4/18) of patients developed metastases. The median follow-up time for all patients after salvage BT was 21 months (range, 8-77 months). Conclusion: Salvage PDR

Local bladder cancer clusters in southeastern Michigan accounting for risk factors, covariates and residential mobility.

Directory of Open Access Journals (Sweden)

Geoffrey M Jacquez

Full Text Available In case control studies disease risk not explained by the significant risk factors is the unexplained risk. Considering unexplained risk for specific populations, places and times can reveal the signature of unidentified risk factors and risk factors not fully accounted for in the case-control study. This potentially can lead to new hypotheses regarding disease causation.Global, local and focused Q-statistics are applied to data from a population-based case-control study of 11 southeast Michigan counties. Analyses were conducted using both year- and age-based measures of time. The analyses were adjusted for arsenic exposure, education, smoking, family history of bladder cancer, occupational exposure to bladder cancer carcinogens, age, gender, and race.Significant global clustering of cases was not found. Such a finding would indicate large-scale clustering of cases relative to controls through time. However, highly significant local clusters were found in Ingham County near Lansing, in Oakland County, and in the City of Jackson, Michigan. The Jackson City cluster was observed in working-ages and is thus consistent with occupational causes. The Ingham County cluster persists over time, suggesting a broad-based geographically defined exposure. Focused clusters were found for 20 industrial sites engaged in manufacturing activities associated with known or suspected bladder cancer carcinogens. Set-based tests that adjusted for multiple testing were not significant, although local clusters persisted through time and temporal trends in probability of local tests were observed.Q analyses provide a powerful tool for unpacking unexplained disease risk from case-control studies. This is particularly useful when the effect of risk factors varies spatially, through time, or through both space and time. For bladder cancer in Michigan, the next step is to investigate causal hypotheses that may explain the excess bladder cancer risk localized to areas of

Adjuvant radiation for vulvar carcinoma: improved local control

International Nuclear Information System (INIS)

Faul, Clare M.; Mirmow, Dwight; Huang Qingshon; Gerszten, Kristina; Day, Roger; Jones, Mirka W.

1997-01-01

Purpose: Local recurrence is a significant problem following primary surgery for advanced vulva carcinoma. The objectives of this study were to evaluate the impact of adjuvant vulvar radiation on local control in high risk patients and the impact of local recurrence on overall survival. Methods and Materials: From 1980-1994, 62 patients with invasive vulva carcinoma and either positive or close (less 8 mm) margins of excision were retrospectively studied. Thirty-one patients were treated with adjuvant radiation therapy to the vulva and 31 patients were observed after surgery. Kaplan-Meier estimates and the Cox proportional hazard regression model were used to evaluate the effect of adjuvant radiation therapy on local recurrence and overall survival. Independent prognostic factors for local recurrence and survival were also assessed. Results: Local recurrence occurred in 58% of observed patients and 16% in patients treated with adjuvant radiation therapy. Adjuvant radiation therapy significantly reduced local recurrence rates in both the close margin and positive margin groups (p = 0.036, p = 0.0048). On both univariate and multivariate analysis adjuvant radiation and margins of excision were significant prognostic predictors for local control. Significant determinants of actuarial survival included International Federation of Gynecologists and Obstetricians (FIGO) stage, percentage of pathologically positive inguinal nodes and margins of excision. The positive margin observed group had a significantly poorer actuarial 5 year survival than the other groups (p = 0.0016) and adjuvant radiation significantly improved survival for this group. The 2 year actuarial survival after developing local recurrence was 25%. Local recurrence was a significant predictor for death from vulva carcinoma (risk ratio 3.54). Conclusion: Local recurrence is a common occurrence in high risk patients. In this study adjuvant radiation therapy significantly reduced local recurrence rates and

Competing-Risks Mortality After Radiotherapy vs. Observation for Localized Prostate Cancer: A Population-based Study

Energy Technology Data Exchange (ETDEWEB)

Abdollah, Firas, E-mail: firas.abdollah@gmail.com [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal (Canada); Department of Urology, Vita Salute San Raffaele University, Milan (Italy); Sun, Maxine [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal (Canada); Schmitges, Jan [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal (Canada); Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg (Germany); Thuret, Rodolphe [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal (Canada); Department of Urology, University of Montpellier Health Centre, Montpellier (France); Tian, Zhe [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal (Canada); Shariat, Shahrokh F. [Department of Urology, Weill Medical College of Cornell University, New York, NY (United States); Briganti, Alberto [Department of Urology, Vita Salute San Raffaele University, Milan (Italy); Jeldres, Claudio; Perrotte, Paul [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal (Canada); Department of Urology, University of Montreal Health Centre, Montreal (Canada); Montorsi, Francesco [Department of Urology, Vita Salute San Raffaele University, Milan (Italy); Karakiewicz, Pierre I. [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal (Canada); Department of Urology, University of Montreal Health Centre, Montreal (Canada)

2012-09-01

Purpose: Contemporary patients with localized prostate cancer (PCa) are more frequently treated with radiotherapy. However, there are limited data on the effect of this treatment on cancer-specific mortality (CSM). Our objective was to test the relationship between radiotherapy and survival in men with localized PCa and compare it with those treated with observation. Methods: A population-based cohort identified 68,797 men with cT1-T2 PCa treated with radiotherapy or observation between the years 1992 and 2005. Propensity-score matching was used to minimize potential bias related to treatment assignment. Competing-risks analyses tested the effect of treatment type (radiotherapy vs. observation) on CSM, after accounting to other-cause mortality. All analyses were carried out within PCa risk, baseline comorbidity status, and age groups. Results: Radiotherapy was associated with more favorable 10-year CSM rates than observation in patients with high-risk PCa (8.8 vs. 14.4%, hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.50-0.68). Conversely, the beneficial effect of radiotherapy on CSM was not evident in patients with low-intermediate risk PCa (3.7 vs. 4.1%, HR: 0.91, 95% CI: 0.80-1.04). Radiotherapy was beneficial in elderly patients (5.6 vs. 7.3%, HR: 0.70, 95% CI: 0.59-0.80). Moreover, it was associated with improved CSM rates among patients with no comorbidities (5.7 vs. 6.5%, HR: 0.81, 95% CI: 0.67-0.98), one comorbidity (4.6 vs. 6.0%, HR: 0.87, 95% CI: 0.75-0.99), and more than two comorbidities (4.2 vs. 5.0%, HR: 0.79, 95% CI: 0.65-0.96). Conclusions: Radiotherapy substantially improves CSM in patients with high-risk PCa, with little or no benefit in patients with low-/intermediate-risk PCa relative to observation. These findings must be interpreted within the context of the limitations of observational data.

An analysis of the 'costs and effectiveness' of post-mastectomy local-regional radiation therapy

International Nuclear Information System (INIS)

Marks, L.B.; Prosnitz, L.R.; Hardenbergh, P.H.; Winer, E.T.

1997-01-01

Purpose: To estimate the 'cost/effectiveness' ratio for post-mastectomy local-regional radiation therapy (LR-XRT) for patients with breast cancer. As the risk of local-regional recurrence (LRR) is related to the number of positive axillary lymph nodes, the cost/effectiveness ratio of LR-XRT was assessed for a variable number of positive axillary nodes. For overall survival (OS), the cost per additional life-year is estimated as a function of follow-up duration. Methods/Assumptions: Literature data indicate that the risk of LRR is related to the number of positive axillary nodes (e.g. Fowble, Kuske). For example, the LRR rate is ∼10% for patients with negative nodes, increasing to ∼40% for patients with ≥4 positive nodes. Such data are used to linearly relate the number of positive nodes with the risk of LRR. Additional assumptions include: RT reduces the risk of LRR by 67%; local recurrences are treated with exision/biopsy, LR-XRT and systemic chemotherapy; half of the local recurrences are controlled locally and half will require additional salvage treatment with surgery or chemotherapy. The 5, 10 and 15 yr improvements in OS provided by LR-XRT are estimated to be 3, 7, and 10%, respectively, based on the literature (Overgaard, Ragaz, Klefstrom, Rutqvist). For each year following LR-XRT, the accrued life-years gained are estimated from the published survival curves. Professional and technical charges are used as a surrogate for costs, as follows (in thousands): LR-XRT-15; evaluation of recurrence-2; biopsy plus pathology-1; resection plus pathology-7, chemotherapy-10. Results: The cost per LRR prevented with the addition of routine post-mastectomy LR-XRT is shown, as a function of the number of positive axillary nodes. The cost per additional life-year gained with LR-XRT, as a function of follow-up duration, is shown. With increasing follow-up, the cost per life-year gained decreases as the additional life-years accrue. Conclusions: The cost per LRR

Increase in protoporphyrin IX after 5-aminolevulinic acid based photodynamic therapy is due to local re-synthesis

NARCIS (Netherlands)

de Bruijn, Henriëtte S.; Kruijt, Bastiaan; van der Ploeg-van den Heuvel, Angélique; Sterenborg, Henricus J. C. M.; Robinson, Dominic J.

2007-01-01

Protoporphyrin IX (PpIX) fluorescence that is bleached during aminolevulinic acid (ALA) mediated photodynamic therapy (PDT) increases again in time after treatment. In the present study we investigated if this increase in PpIX fluorescence after illumination is the result of local re-synthesis or of

Dosimetric comparison of axilla and groin radiotherapy techniques for high-risk and locally advanced skin cancer

International Nuclear Information System (INIS)

Mattes, Malcolm D.; Zhou, Ying; Berry, Sean L.; Barker, Christopher A.

2016-01-01

Radiation therapy targeting axilla and groin lymph nodes improves regional disease control in locally advanced and high-risk skin cancers. However, trials generally used conventional two-dimensional radiotherapy (2D-RT), contributing towards relatively high rates of side effects from treatment. The goal of this study is to determine if three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or volumetric-modulated arc therapy (VMAT) may improve radiation delivery to the target while avoiding organs at risk in the clinical context of skin cancer regional nodal irradiation. Twenty patients with locally advanced/high-risk skin cancers underwent computed tomography simulation. The relevant axilla or groin planning target volumes and organs at risk were delineated using standard definitions. Paired t-tests were used to compare the mean values of several dose-volumetric parameters for each of the 4 techniques. In the axilla, the largest improvement for 3D-CRT compared to 2D-RT was for homogeneity index (13.9 vs. 54.3), at the expense of higher lung V 20 (28.0% vs. 12.6%). In the groin, the largest improvements for 3D-CRT compared to 2D-RT were for anorectum D max (13.6 vs. 38.9 Gy), bowel D 200cc (7.3 vs. 23.1 Gy), femur D 50 (34.6 vs. 57.2 Gy), and genitalia D max (37.6 vs. 51.1 Gy). IMRT had further improvements compared to 3D-CRT for humerus D mean (16.9 vs. 22.4 Gy), brachial plexus D 5 (57.4 vs. 61.3 Gy), bladder D 5 (26.8 vs. 36.5 Gy), and femur D 50 (18.7 vs. 34.6 Gy). Fewer differences were observed between IMRT and VMAT. Compared to 2D-RT and 3D-CRT, IMRT and VMAT had dosimetric advantages in the treatment of nodal regions of skin cancer patients

Dosimetric comparison of axilla and groin radiotherapy techniques for high-risk and locally advanced skin cancer

Energy Technology Data Exchange (ETDEWEB)

Mattes, Malcolm D.; Zhou, Ying; Berry, Sean L.; Barker, Christopher A. [Memorial Sloan Kettering Cancer Center, New York (United States)

2016-06-15

Radiation therapy targeting axilla and groin lymph nodes improves regional disease control in locally advanced and high-risk skin cancers. However, trials generally used conventional two-dimensional radiotherapy (2D-RT), contributing towards relatively high rates of side effects from treatment. The goal of this study is to determine if three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or volumetric-modulated arc therapy (VMAT) may improve radiation delivery to the target while avoiding organs at risk in the clinical context of skin cancer regional nodal irradiation. Twenty patients with locally advanced/high-risk skin cancers underwent computed tomography simulation. The relevant axilla or groin planning target volumes and organs at risk were delineated using standard definitions. Paired t-tests were used to compare the mean values of several dose-volumetric parameters for each of the 4 techniques. In the axilla, the largest improvement for 3D-CRT compared to 2D-RT was for homogeneity index (13.9 vs. 54.3), at the expense of higher lung V{sub 20} (28.0% vs. 12.6%). In the groin, the largest improvements for 3D-CRT compared to 2D-RT were for anorectum D{sub max} (13.6 vs. 38.9 Gy), bowel D{sub 200cc} (7.3 vs. 23.1 Gy), femur D{sub 50} (34.6 vs. 57.2 Gy), and genitalia D{sub max} (37.6 vs. 51.1 Gy). IMRT had further improvements compared to 3D-CRT for humerus D{sub mean} (16.9 vs. 22.4 Gy), brachial plexus D{sub 5} (57.4 vs. 61.3 Gy), bladder D{sub 5} (26.8 vs. 36.5 Gy), and femur D{sub 50} (18.7 vs. 34.6 Gy). Fewer differences were observed between IMRT and VMAT. Compared to 2D-RT and 3D-CRT, IMRT and VMAT had dosimetric advantages in the treatment of nodal regions of skin cancer patients.

Very High-Risk Localized Prostate Cancer: Outcomes Following Definitive Radiation

International Nuclear Information System (INIS)

Narang, Amol K.; Gergis, Carol; Robertson, Scott P.; He, Pei; Ram, Ashwin N.; McNutt, Todd R.; Griffith, Emily; DeWeese, Theodore A.; Honig, Stephanie; Singh, Harleen; Song, Danny Y.; Tran, Phuoc T.; DeWeese, Theodore L.

2016-01-01

criteria experience distinctly worse outcomes following definitive radiation and long-term androgen deprivation therapy, particularly if an EOR PSA is detectable. Optimal use of local therapies for VHR patients should be explored further, as should novel agents.

Proton therapy for tumors of the skull base

Energy Technology Data Exchange (ETDEWEB)

Munzenrider, J.E.; Liebsch, N.J. [Dept. of Radiation Oncology, Harvard Univ. Medical School, Boston, MA (United States)

1999-06-01

Charged particle beams are ideal for treating skull base and cervical spine tumors: dose can be focused in the target, while achieving significant sparing of the brain, brain stem, cervical cord, and optic nerves and chiasm. For skull base tumors, 10-year local control rates with combined proton-photon therapy are highest for chondrosarcomas, intermediate for male chordomas, and lowest for female chordomas (94%, 65%, and 42%, respectively). For cervical spine tumors, 10-year local control rates are not significantly different for chordomas and chondrosarcomas (54% and 48%, respectively), nor is there any difference in local control between males and females. Observed treatment-related morbidity has been judged acceptable, in view of the major morbidity and mortality which accompany uncontrolled tumor growth. (orig.)

Proton therapy for tumors of the skull base

International Nuclear Information System (INIS)

Munzenrider, J.E.; Liebsch, N.J.

1999-01-01

Charged particle beams are ideal for treating skull base and cervical spine tumors: dose can be focused in the target, while achieving significant sparing of the brain, brain stem, cervical cord, and optic nerves and chiasm. For skull base tumors, 10-year local control rates with combined proton-photon therapy are highest for chondrosarcomas, intermediate for male chordomas, and lowest for female chordomas (94%, 65%, and 42%, respectively). For cervical spine tumors, 10-year local control rates are not significantly different for chordomas and chondrosarcomas (54% and 48%, respectively), nor is there any difference in local control between males and females. Observed treatment-related morbidity has been judged acceptable, in view of the major morbidity and mortality which accompany uncontrolled tumor growth. (orig.)

Comparative Cost-Effectiveness of Stereotactic Body Radiation Therapy Versus Intensity-Modulated and Proton Radiation Therapy for Localized Prostate Cancer

International Nuclear Information System (INIS)

Parthan, Anju; Pruttivarasin, Narin; Davies, Diane; Taylor, Douglas C. A.; Pawar, Vivek; Bijlani, Akash; Lich, Kristen Hassmiller; Chen, Ronald C.

2012-01-01

Objective: To determine the cost-effectiveness of several external beam radiation treatment modalities for the treatment of patients with localized prostate cancer. Methods: A lifetime Markov model incorporated the probabilities of experiencing treatment-related long-term toxicity or death. Toxicity probabilities were derived from published sources using meta-analytical techniques. Utilities and costs in the model were obtained from publicly available secondary sources. The model calculated quality-adjusted life expectancy and expected lifetime cost per patient, and derived ratios of incremental cost per quality-adjusted life year (QALY) gained between treatments. Analyses were conducted from both payer and societal perspectives. One-way and probabilistic sensitivity analyses were performed. Results: Compared to intensity-modulated radiation therapy (IMRT) and proton beam therapy (PT), stereotactic body radiation therapy (SBRT) was less costly and resulted in more QALYs. Sensitivity analyses showed that the conclusions in the base-case scenario were robust with respect to variations in toxicity and cost parameters consistent with available evidence. At a threshold of $50,000/QALY, SBRT was cost-effective in 75% and 94% of probabilistic simulations compared to IMRT and PT, respectively, from a payer perspective. From a societal perspective, SBRT was cost-effective in 75% and 96% of simulations compared to IMRT and PT, respectively, at a threshold of $50,000/QALY. In threshold analyses, SBRT was less expensive with better outcomes compared to IMRT at toxicity rates 23% greater than the SBRT base-case rates. Conclusion: Based on the assumption that each treatment modality results in equivalent long-term efficacy, SBRT is a cost-effective strategy resulting in improved quality-adjusted survival compared to IMRT and PT for the treatment of localized prostate cancer.

Early experience of proton beam therapy combined with chemotherapy for locally advanced oropharyngeal cancer

International Nuclear Information System (INIS)

Ishikawa, Youjirou; Nakamura, Tatsuya; Takada, Akinori; Takayama, Kanako; Makita, Chiyoko; Suzuki, Motohisa; Azami, Yusuke; Kikuchi, Yasuhiro; Fuwa, Nobukazu

2013-01-01

Between 2009 and 2012, 10 patients with advanced oropharyngeal cancer underwent proton therapy combined with chemotherapy. The initial results of this therapy were 8 complete response (CR) and 2 partial response (PR), local recurrence was detected 1 patient. Proton beam therapy combined with chemotherapy is thought to be an effective treatment for locally advanced oropharyngeal cancer. (author)

Improved outcome for children with acute lymphoblastic leukemia after risk-adjusted intensive therapy: a single institution experience

International Nuclear Information System (INIS)

Al-Nasser, A.; El-Solh, H.; Al-Mahr, M.

2008-01-01

Because of need for more comprehensive information on the least toxic and most effective forms of therapy for children with acute lymphoblastic leukemia (ALL), we reviewed our experience in the treatment of children with ALL at King Faisal Specialist Hospital and Research Centre (KFSHRC) and King Fahd National Center for Children's Cancer and Research (KFNCCCR) over a period of 18 years with a focus on patient characteristics and outcome. During the period of 1981 to 1988, records of children with ALL were retrospectively reviewed with respect to clinical presentation, laboratory findings, risk factors, stratification, therapy and outcome. The protocols used in treatment included 4 local protocols (KFSH 81, 84, 87 and 90) and subsequently. Children's Cancer Group (CCG) protocols and these were grouped as Era (1981-1992) and Era 2 (1993-1998). Of 509 children with ALL treated during this period, 316 were treated using local protocols and 193 using CCG protocols. Drugs used in Era 1 included a 4-drug induction using etoposid (VP-16) instead of L-asparaginase. Consolidation was based on high dose methotexate (MTX) 1g/m2 and maintenance was based on oral mercaptopurine (6-MP) and MTX with periodic pulses using intravenous teniposide (VM-26), Ara-C, L-asparaginase, adriamycin, prednisone, VP-16 cyclophosphamide .International protocols were introduced in Era 2, which was also marked by intensification of early treatment, a wider selection of cytoreductive agents, and the alternating use of non-cross-resistant pairs of drugs using the post-remission period. The end of induction remission rate improved from 90% in Era 1 to 95% in Era 2, which was of borderline statistical significance (P=0.49). The 5-year event-free survival (EFS) improved from 30.6% in Era 1 to 64.2% in Era 2 (P<.001). Improvement in outcome was achieved without any significant increase in morbidity or mortality, due to improvement in both systemic therapy and supportive care. The most important

Hormone replacement therapy and risk of glioma

DEFF Research Database (Denmark)

Andersen, Lene; Friis, Søren; Hallas, Jesper

2013-01-01

Aim: Several studies indicate that use of hormone replacement therapy (HRT) is associated with an increased risk of intracranial meningioma, while associations between HRT use and risk of other brain tumors have been less explored. We investigated the influence of HRT use on the risk of glioma...

A phase III comparison of radiation therapy with or without recombinant β-interferon for poor-risk patients with locally advanced non-small-cell lung cancer (RTOG 93-04)

International Nuclear Information System (INIS)

Bradley, Jeffrey D.; Scott, Charles B.; Paris, Kristie J.; Demas, William F.; Machtay, Mitchell; Komaki, Ritsuko; Movsas, Benjamin; Rubin, Philip; Sause, William T.

2002-01-01

Purpose: The results of Phase I/II data testing β-interferon with radiation therapy in a non-small-cell lung cancer population were promising. Based on these data, the Radiation Therapy Oncology Group (RTOG) initiated a Phase III trial to test the efficacy of β-interferon in poor-risk patients with Stages IIIA and IIIB non-small-cell lung carcinoma. Methods: Between September 1994 and March 1998, 123 patients were accrued to this trial. Enrolled patients were not eligible for other chemoradiation studies within the RTOG. Eligibility criteria included histologically confirmed Stage IIIA or IIIB non-small-cell lung cancer (according to American Joint Committee on Cancer) considered clinically inoperable or unresectable at the time of surgery. Patients were required to have a Karnofsky performance status 50-70 or >70 and at least 5% weight loss over the preceding 3 months. Betaseron (recombinant human interferon beta ser , rHuIFN-β ser ,) was the chosen preparation of β-interferon. The patients randomized to the investigational arm received 16x10 6 IU of Betaseron by i.v. bolus given 3 days a week (Monday-Wednesday) on Weeks 1, 3, and 5. The Betaseron was given 30 minutes before radiation therapy for a total of nine doses. Irradiation was delivered at 2 Gy per fraction, 5 days a week, for a total of 60 Gy over 6 weeks and was identical for both arms. The primary end point of the trial was overall survival with local control as a secondary end point. Toxicities occurring within 90 days of therapy completion were defined as acute. Results: The median follow-up was 4 years (range: 2.5-6 years) for surviving patients. Seventy-six percent of all patients completed β-interferon. Toxicity was the primary reason for noncompliance. Radiotherapy (RT) compliance was excellent in the RT-alone arm, with 94% completing therapy, compared to 82% in the β-interferon arm (p=0.0475). Grade 3 and 4 acute toxicities were higher on the β-interferon arm (p=0.0249). Grade 3 and 4

Androgen deprivation therapy and cardiovascular risk in patients with prostate cancer

International Nuclear Information System (INIS)

Khan, M.Y.; Haider, N.; Rasul, S.; Mahmood, A.; Nadeem, M.S.

2017-01-01

The objective of this study was to investigate the effects of androgen deprivation therapy (ADT) on risk of subsequent cardiovascular morbidity in men with prostate cancer. Study Design: Quasi experimental study. Place and Duration of Study: Department of oncology Combined Military Hospital Rawalpindi, from Sep 2014 to May 2015. Patients and Methods: Thirty consecutive patients fulfilling inclusion criteria were enrolled. All patients were subjected to medical castration/ androgen deprivation therapy (ADT) with monthly 3.75 mg leuprorelin acetate intramuscular injection until castrate levels of testosterone (<50ng/dL) were achieved. We used Framingham's score for assessment of 10 years cardiovascular risk of individual patient before initiation and after completion of 6 months ADT. Serum lipid profile (fasting), systolic blood pressure, history of smoking, diabetes and antihypertensive medication were recorded. Proforma was designed to get clinical information. A p-value of <0.05 was considered significant. A paired-samples t-test was conducted to compare Framingham cardiovascular risk scores before initiation and after completion of 6 months ADT. Results: We enrolled 30 men with high/intermediate risk localized prostate cancer. Mean age was 63.47 +- 7.32 years. All patients received 6 months ADT with monthly 3.75mg leuprorelin acetate intramuscular injection. There was a significant difference in Framingham cardiovascular risk scores before (mean +- sd; 20.95 +- 7.98) and after (mean +- sd; 25.72 +- 6.15) 6 months ADT; t (29) =-4.54, p<0.01, two-tailed. Hence ADT resulted in a significant increase (mean +- sd; 25.7 +- 6.15) in 10 years cardiovascular morbidity risk t (29) =-4.54, p<0.01, two tailed. Subset analyses revealed significant increase in fasting serum total cholesterol, triglycerides and Low density lipoprotein (LDL) levels after 6 months ADT (p<0.01, <0.01 and <0.01 respectively) however high density lipoprotein (HDL) remained un-changed (p=0.043) in

Systemic and localized infection by Candida species in patients with rheumatic diseases receiving anti-TNF therapy

Directory of Open Access Journals (Sweden)

Nadia E. Aikawa

Full Text Available ABSTRACT Objective: To evaluate the prevalence of systemic and localized infection by Candida species and its possible association with demographic, clinical and laboratory manifestations and therapy in patients with rheumatic diseases taking TNF blockers. Methods: Consecutive patients with rheumatic diseases receiving anti-TNF agents were included. The following risk factors up to four weeks prior to the study were analyzed: use of antibiotics, immunosuppressant drugs, hospitalization and invasive procedures. All subjects were evaluated for clinical complaints; specific blood cultures were obtained for fungi and blood samples were collected for Candida spp. detection by polymerase chain reaction. Results: 194 patients [67 with rheumatoid arthritis (RA, 47 with ankylosing spondylitis (AS, 36 with juvenile idiopathic arthritis (JIA, 28 with psoriatic arthritis and 16 with other conditions] were included. The average age of patients was 42 ± 16 years, with 68 (35% male and mean disease duration of 15 ± 10 years. Sixty-four (33% patients were receiving adalimumab, 59 (30% etanercept and 71 (36% infliximab. Eighty-one percent of patients were concomitantly taking immunosuppressant drugs. At the time of the study, only one (0.5% patient had localized fungal infection (vaginal candidiasis. None of the patients included had systemic candidiasis with positive blood cultures for fungi or PCR positive for Candida spp. in peripheral blood sample. Conclusions: This was the first study to assess the prevalence of invasive and localized fungal disease by Candida in a significant number of patients with rheumatic diseases on anti-TNF therapy, and demonstrated low risk of candidiasis, despite the high prevalence of immunosuppressive drug use.

Determining diabetic retinopathy screening interval based on time from no retinopathy to laser therapy.

Science.gov (United States)

Hughes, Daniel; Nair, Sunil; Harvey, John N

2017-12-01

Objectives To determine the necessary screening interval for retinopathy in diabetic patients with no retinopathy based on time to laser therapy and to assess long-term visual outcome following screening. Methods In a population-based community screening programme in North Wales, 2917 patients were followed until death or for approximately 12 years. At screening, 2493 had no retinopathy; 424 had mostly minor degrees of non-proliferative retinopathy. Data on timing of first laser therapy and visual outcome following screening were obtained from local hospitals and ophthalmology units. Results Survival analysis showed that very few of the no retinopathy at screening group required laser therapy in the early years compared with the non-proliferative retinopathy group ( p retinopathy at screening group required laser therapy, and at three years 0.2% (cumulative), lower rates of treatment than have been suggested by analyses of sight-threatening retinopathy determined photographically. At follow-up (mean 7.8 ± 4.6 years), mild to moderate visual impairment in one or both eyes due to diabetic retinopathy was more common in those with retinopathy at screening (26% vs. 5%, p diabetes occurred in only 1 in 1000. Conclusions Optimum screening intervals should be determined from time to active treatment. Based on requirement for laser therapy, the screening interval for diabetic patients with no retinopathy can be extended to two to three years. Patients who attend for retinal screening and treatment who have no or non-proliferative retinopathy now have a very low risk of eventual blindness from diabetes.

Nodal Clearance Rate and Long-Term Efficacy of Individualized Sentinel Node–Based Pelvic Intensity Modulated Radiation Therapy for High-Risk Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Müller, Arndt-Christian, E-mail: arndt-christian.mueller@med.uni-tuebingen.de [Department of Radiation Oncology, Eberhard Karls University, Tübingen (Germany); Eckert, Franziska; Paulsen, Frank; Zips, Daniel [Department of Radiation Oncology, Eberhard Karls University, Tübingen (Germany); Stenzl, Arnulf; Schilling, David [Department of Urology, Eberhard Karls University, Tübingen (Germany); Alber, Markus [Department of Oncology, Aarhus University, Aarhus (Denmark); Bares, Roland [Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard Karls University, Tübingen (Germany); Martus, Peter [Institute for Clinical Epidemiology and Applied Biometry, Eberhard Karls University, Tübingen (Germany); Weckermann, Dorothea [Department of Urology, Klinikum Augsburg, Augsburg (Germany); Belka, Claus; Ganswindt, Ute [Department of Radiation Oncology, Ludwig-Maximilians-University, Munich (Germany)

2016-02-01

Purpose: To assess the efficacy of individual sentinel node (SN)-guided pelvic intensity modulated radiation therapy (IMRT) by determining nodal clearance rate [(n expected nodal involvement − n observed regional recurrences)/n expected nodal involvement] in comparison with surgically staged patients. Methods and Materials: Data on 475 high-risk prostate cancer patients were examined. Sixty-one consecutive patients received pelvic SN-based IMRT (5 × 1.8 Gy/wk to 50.4 Gy [pelvic nodes + individual SN] and an integrated boost with 5 × 2.0 Gy/wk to 70.0 Gy to prostate + [base of] seminal vesicles) and neo-/adjuvant long-term androgen deprivation therapy; 414 patients after SN–pelvic lymph node dissection were used to calculate the expected nodal involvement rate for the radiation therapy sample. Biochemical control and overall survival were estimated for the SN-IMRT patients using the Kaplan-Meier method. The expected frequency of nodal involvement in the radiation therapy group was estimated by imputing frequencies of node-positive patients in the surgical sample to the pattern of Gleason, prostate-specific antigen, and T category in the radiation therapy sample. Results: After a median follow-up of 61 months, 5-year OS after SN-guided IMRT reached 84.4%. Biochemical control according to the Phoenix definition was 73.8%. The nodal clearance rate of SN-IMRT reached 94%. Retrospective follow-up evaluation is the main limitation. Conclusions: Radiation treatment of pelvic nodes individualized by inclusion of SNs is an effective regional treatment modality in high-risk prostate cancer patients. The pattern of relapse indicates that the SN-based target volume concept correctly covers individual pelvic nodes. Thus, this SN-based approach justifies further evaluation, including current dose-escalation strategies to the prostate in a larger prospective series.

Validation of High-Risk Computed Tomography Features for Detection of Local Recurrence After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Peulen, Heike [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Mantel, Frederick [Department of Radiation Oncology, University of Wuerzburg, Wuerzburg (Germany); Department of Radiation Oncology, University Hospital Zurich, Zurich (Switzerland); Guckenberger, Matthias [Department of Radiation Oncology, University of Wuerzburg, Wuerzburg (Germany); Belderbos, José [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Werner-Wasik, Maria [Department of Radiation Oncology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Hope, Andrew; Giuliani, Meredith [Department of Radiation Oncology University of Toronto and Princess Margaret Cancer Center, Toronto, Ontario (Canada); Grills, Inga [Department of Radiation Oncology Beaumont Hospital, Royal Oak, Michigan (United States); Sonke, Jan-Jakob, E-mail: j.sonke@nki.nl [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands)

2016-09-01

Purpose: Fibrotic changes after stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC) are difficult to distinguish from local recurrences (LR), hampering proper patient selection for salvage therapy. This study validates previously reported high-risk computed tomography (CT) features (HRFs) for detection of LR in an independent patient cohort. Methods and Materials: From a multicenter database, 13 patients with biopsy-proven LR were matched 1:2 to 26 non-LR control patients based on dose, planning target volume (PTV), follow-up time, and lung lobe. Tested HRFs were enlarging opacity, sequential enlarging opacity, enlarging opacity after 12 months, bulging margin, linear margin disappearance, loss of air bronchogram, and craniocaudal growth. Additionally, 2 new features were analyzed: the occurrence of new unilateral pleural effusion, and growth based on relative volume, assessed by manual delineation. Results: All HRFs were significantly associated with LR except for loss of air bronchogram. The best performing HRFs were bulging margin, linear margin disappearance, and craniocaudal growth. Receiver operating characteristic analysis of the number of HRFs to detect LR had an area under the curve (AUC) of 0.97 (95% confidence interval [CI] 0.9-1.0), which was identical to the performance described in the original report. The best compromise (closest to 100% sensitivity and specificity) was found at ≥4 HRFs, with a sensitivity of 92% and a specificity of 85%. A model consisting of only 2 HRFs, bulging margin and craniocaudal growth, resulted in a sensitivity of 85% and a specificity of 100%, with an AUC of 0.96 (95% CI 0.9-1.0) (HRFs ≥2). Pleural effusion and relative growth did not significantly improve the model. Conclusion: We successfully validated CT-based HRFs for detection of LR after SBRT for early-stage NSCLC. As an alternative to number of HRFs, we propose a simplified model with the combination of the 2 best HRFs

Assessment of global and local region-based bilateral mammographic feature asymmetry to predict short-term breast cancer risk

Science.gov (United States)

Li, Yane; Fan, Ming; Cheng, Hu; Zhang, Peng; Zheng, Bin; Li, Lihua

2018-01-01

This study aims to develop and test a new imaging marker-based short-term breast cancer risk prediction model. An age-matched dataset of 566 screening mammography cases was used. All ‘prior’ images acquired in the two screening series were negative, while in the ‘current’ screening images, 283 cases were positive for cancer and 283 cases remained negative. For each case, two bilateral cranio-caudal view mammograms acquired from the ‘prior’ negative screenings were selected and processed by a computer-aided image processing scheme, which segmented the entire breast area into nine strip-based local regions, extracted the element regions using difference of Gaussian filters, and computed both global- and local-based bilateral asymmetrical image features. An initial feature pool included 190 features related to the spatial distribution and structural similarity of grayscale values, as well as of the magnitude and phase responses of multidirectional Gabor filters. Next, a short-term breast cancer risk prediction model based on a generalized linear model was built using an embedded stepwise regression analysis method to select features and a leave-one-case-out cross-validation method to predict the likelihood of each woman having image-detectable cancer in the next sequential mammography screening. The area under the receiver operating characteristic curve (AUC) values significantly increased from 0.5863  ±  0.0237 to 0.6870  ±  0.0220 when the model trained by the image features extracted from the global regions and by the features extracted from both the global and the matched local regions (p  =  0.0001). The odds ratio values monotonically increased from 1.00-8.11 with a significantly increasing trend in slope (p  =  0.0028) as the model-generated risk score increased. In addition, the AUC values were 0.6555  ±  0.0437, 0.6958  ±  0.0290, and 0.7054  ±  0.0529 for the three age groups of 37

Radiation Therapy to the Primary and Postinduction Chemotherapy MIBG-Avid Sites in High-Risk Neuroblastoma

Energy Technology Data Exchange (ETDEWEB)

Mazloom, Ali; Louis, Chrystal U.; Nuchtern, Jed; Kim, Eugene; Russell, Heidi; Allen-Rhoades, Wendy; Krance, Robert; Paulino, Arnold C., E-mail: apaulino@mdanderson.org

2014-11-15

Purpose: Although it is generally accepted that consolidation therapy for neuroblastoma includes irradiation of the primary site and any remaining metaiodobenzylguanidine (MIBG)-avid metastatic sites, limited information has been published regarding the efficacy of this approach. Methods and Materials: Thirty patients with high-risk neuroblastoma were treated at 1 radiation therapy (RT) department after receiving 5 cycles of induction chemotherapy and resection. All patients had at least a partial response after induction therapy, based upon international neuroblastoma response criteria. The primary sites were treated with 24 to 30 Gy whereas the MIBG-avid metastatic sites were treated with 24 Gy. RT was followed by high-dose chemotherapy with autologous stem cell rescue and 6 months of cis-retinoic acid. Results: The 5-year progression-free survival (PFS) and overall survival (OS) rates were 48% and 59%, respectively. The 5-year locoregional control at the primary site was 84%. There were no differences in locoregional control according to degree of primary surgical resection. The 5-year local control rate for metastatic sites was 74%. The 5-year PFS rates for patients with 0, 1, 2, and >3 postinduction MIBG sites were 66%, 57%, 20%, and 0% (P<.0001), respectively, whereas 5-year OS rates were 80%, 57%, 50%, and 0%, respectively (P<.0001). Conclusions: RT to the primary site and postinduction MIBG-positive metastatic sites was associated with 84% and 74% local control, respectively. The number of MIBG-avid sites present after induction chemotherapy and surgery was predictive of progression-free and overall survival.

Local Risk-Minimization for Defaultable Claims with Recovery Process

International Nuclear Information System (INIS)

Biagini, Francesca; Cretarola, Alessandra

2012-01-01

We study the local risk-minimization approach for defaultable claims with random recovery at default time, seen as payment streams on the random interval [0,τ∧T], where T denotes the fixed time-horizon. We find the pseudo-locally risk-minimizing strategy in the case when the agent information takes into account the possibility of a default event (local risk-minimization with G-strategies) and we provide an application in the case of a corporate bond. We also discuss the problem of finding a pseudo-locally risk-minimizing strategy if we suppose the agent obtains her information only by observing the non-defaultable assets.

Efficacy and Safety of Adjuvant Proton Therapy Combined With Surgery for Chondrosarcoma of the Skull Base: A Retrospective, Population-Based Study

Energy Technology Data Exchange (ETDEWEB)

Feuvret, Loïc, E-mail: loic.feuvret@psl.aphp.fr [Department of Radiation Oncology, Groupe Hospitalier La Pitié-Salpêtrière–Charles Foix (Assistance Publique–Hôpitaux de Paris), Paris (France); Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d' Orsay (CPO), Orsay (France); Bracci, Stefano [Institute of Radiation Oncology, Sapienza University, Sant' Andrea Hospital, Rome (Italy); Calugaru, Valentin [Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d' Orsay (CPO), Orsay (France); Bolle, Stéphanie [Department of Radiation Oncology, Gustave Roussy, Villejuif (France); Mammar, Hamid; De Marzi, Ludovic [Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d' Orsay (CPO), Orsay (France); Bresson, Damien [Department of Neurosurgery, Hôpital Lariboisière (Assistance Publique–Hôpitaux de Paris), Paris (France); Habrand, Jean-Louis [Department of Radiation Oncology, Centre François Baclesse, Caen (France); Mazeron, Jean-Jacques [Department of Radiation Oncology, Groupe Hospitalier La Pitié-Salpêtrière–Charles Foix (Assistance Publique–Hôpitaux de Paris), Paris (France); Dendale, Rémi [Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d' Orsay (CPO), Orsay (France); and others

2016-05-01

Purpose: Chondrosarcoma is a rare malignant tumor of the cartilage affecting young adults. Surgery, followed by charged-particle irradiation, is considered the reference standard for the treatment of patients with grade I to II skull base chondrosarcoma. The present study was conducted to assess the effect of the quality of surgery and radiation therapy parameters on local control (LC) and overall survival (OS). Methods and Materials: From 1996 to 2013, 159 patients (median age 40 years, range 12-83) were treated with either protons alone or a combination of protons and photons. The median total dose delivered was 70.2 Gy (relative biologic effectiveness [RBE]; range 67-71). Debulking and biopsy were performed in 133 and 13 patients, respectively. Results: With a median follow-up of 77 months (range 2-214), 5 tumors relapsed based on the initial gross tumor volume. The 5- and 10-year LC rates were 96.4% and 93.5%, respectively, and the 5- and 10-year OS rates were 94.9% and 87%, respectively. A total of 16 patients died (13 of intercurrent disease, 3 of disease progression). On multivariate analysis, age <40 years and primary disease status were independent favorable prognostic factors for progression-free survival and OS, and local tumor control was an independent favorable predictor of OS. In contrast, the extent of surgery, dosimetric parameters, and adjacent organs at risk were not prognostic factors for LC or OS. Conclusions: Systematic high-dose postoperative proton therapy for skull base chondrosarcoma can achieve a high LC rate with a low toxicity profile. Maximal safe surgery, followed by high-dose conformal proton therapy, is therefore recommended.

Investigating the experiences in a school-based occupational therapy program to inform community-based paediatric occupational therapy practice.

Science.gov (United States)

Rens, Lezahn; Joosten, Annette

2014-06-01

A collaborative approach with teachers is required when providing community-based occupational therapy to educationally at risk children. Collaborators share common goals and interact and support each other but challenges arise in providing collaborative occupational therapy in settings outside the school environment. The aim of this study was to capture experiences of teachers and occupational therapists working within a school-based occupational therapy program to determine if their experiences could inform collaborative practice. In this pilot study, participant responses to questionnaires (n = 32) about their experiences formed the basis for focus groups and individual interviews. Two focus group were conducted, one with teachers (n = 11) and one with occupational therapy participants (n = 6). Individual interviews were conducted with the supervising occupational therapist, school principal and two leading teachers. Descriptive statistics were used to analyse the data from closed questions, and thematic analysis using a constant comparison approach was used to analyse open ended questions, focus groups and interviews. Three main themes emerged: (i) the need for occupational therapists to spend time in the school, to explain their role, build relationships, understand classroom routines and the teacher role; (ii) occupational therapists need to not see themselves as the expert but develop equal partnerships to set collaborative goals and (iii) occupational therapists advocating for all parties to be informed throughout the occupational therapy process. The pilot study findings identified teacher and therapist experiences within the school setting that could inform improved collaborative practice with teachers and community-based occupational therapists and these findings warrant further investigation. © 2013 Occupational Therapy Australia.

Comparative cost-effectiveness of stereotactic body radiation therapy versus intensity-modulated and proton radiation therapy for localized prostate cancer.

Directory of Open Access Journals (Sweden)

Anju eParthan

2012-08-01

Full Text Available Objective. To determine the cost-effectiveness of several external beam radiation treatment modalities for the treatment of patients with localized prostate cancer.Methods. A lifetime Markov model incorporated the probabilities of experiencing treatment-related long-term toxicity or death. Toxicity probabilities were derived from published sources using meta-analytical techniques. Utilities and costs in the model were obtained from publically available secondary sources. The model calculated quality-adjusted life expectancy and expected lifetime cost per patient, and derived ratios of incremental cost per quality-adjusted life year (QALY gained between treatments. Analyses were conducted from both a payer and societal perspectives. One-way and probabilistic sensitivity analyses were performed.Results. Compared to intensity modulated radiation therapy (IMRT and proton beam therapy (PT, stereotactic body radiation therapy (SBRT was less costly and resulted in more QALYs. Sensitivity analyses showed that the conclusions in the base-case scenario were robust with respect to variations in toxicity and cost parameters consistent with available evidence. At a threshold of $50,000/QALY, SBRT was cost effective in 75%, and 94% of probabilistic simulations compared to IMRT and PT, respectively, from a payer perspective. From a societal perspective, SBRT was cost-effective in 75%, and 96% of simulations compared to IMRT and PT, respectively, at a threshold of $50,000/QALY. In threshold analyses, SBRT was less expensive with better outcomes compared to IMRT at toxicity rates 23% greater than the SBRT base-case rates. Conclusions. Based on the assumption that each treatment modality results in equivalent long-term efficacy, SBRT is a cost-effective strategy resulting in improved quality-adjusted survival compared to IMRT and PT for the treatment of localized prostate cancer.

Oral surgery in patients under antithrombotic therapy: perioperative bleeding as a significant risk factor for postoperative hemorrhage.

Science.gov (United States)

Rocha, Amanda L; Souza, Alessandra F; Martins, Maria A P; Fraga, Marina G; Travassos, Denise V; Oliveira, Ana C B; Ribeiro, Daniel D; Silva, Tarcília A

2018-01-01

: To investigate perioperative and postoperative bleeding, complications in patients under therapy with anticoagulant or antiplatelet drugs submitted to oral surgery. To evaluate the risk of bleeding and safety for dental surgery, a retrospective chart review was performed. Medical and dental records of patients taking oral antithrombotic drugs undergoing dental surgery between 2010 and 2015 were reviewed. Results were statistically analyzed using Fisher's exact test, t test or the χ test. One hundred and seventy-nine patients underwent 293 surgical procedures. A total of eight cases of perioperative and 12 episodes of postoperative bleeding were documented. The complications were generally managed with local measures and did not require hospitalization. We found significant association of postoperative hemorrhage with increased perioperative bleeding (P = 0.043) and combination of anticoagulant and antiplatelet therapy (P bleeding is 8.8 times bigger than procedures without perioperative bleeding. Dental surgery in patients under antithrombotic therapy might be carried out without altering the regimen because of low risk of perioperative and postoperative bleeding. However, patients with increased perioperative bleeding should be closely followed up because of postoperative complications risk.

Risk of fracture in adults on renal replacement therapy

DEFF Research Database (Denmark)

Hansen, Ditte; Olesen, Jonas B; Gislason, Gunnar H

2016-01-01

BACKGROUND: Patients on dialysis treatment or living with a transplanted kidney have several risk factors for bone fracture, especially disturbances in mineral metabolism and immunosuppressive therapy. We describe the incidence of fracture in this retrospective national Danish cohort study and ex....... Differences in age, gender, drug use and comorbidity only partly explain this increased risk. Further studies are warranted to explore the reason for this increased fracture risk in patients on renal replacement therapy....

Risks and safety of combination therapy for hypothyroidism.

Science.gov (United States)

Jonklaas, Jacqueline

2016-08-01

Hypothyroidism is currently a condition that can be treated, but not cured. Although levothyroxine reverses stigmata of hypothyroidism in most individuals, some patients feel dissatisfied with 'monotherapy', and this has stimulated interest in 'combination therapy' with both levothyroxine and liothyronine. A search of PubMed was conducted using terms including hypothyroidism, treatment, benefits, risks, and safety. Based on the articles identified, the body of evidence regarding the efficacy of traditional levothyroxine is reviewed. Concerns with levothyroxine therapy including impaired quality of life in treated patients, thyroxine-predominant hormone ratios, and inadvertent iatrogenic thyroid disease are discussed. The trials of combination therapy performed since 1999 were reviewed. The heterogeneity of these trials, both in terms of design and results, is discussed. The potential for new trials to determine whether combination therapy can reverse the dissatisfaction associated with monotherapy, while avoiding non-physiologic hormone ratios, inadvertent thyrotoxicosis, and unacceptable side effects is discussed. Expert commentary: Research regarding which therapy fully reverses hypothyroidism at a tissue and cellular level is ongoing. The field would be advanced by the development of an extended release preparation of liothyronine. In the future regeneration of functional thyroid follicles from stem cells may offer hope for curing hypothyroidism.

On the cost-effectiveness of Carbon ion radiation therapy for skull base chordoma

International Nuclear Information System (INIS)

Jaekel, Oliver; Land, Beate; Combs, Stephanie Elisabeth; Schulz-Ertner, Daniela; Debus, Juergen

2007-01-01

Aim: The cost-effectiveness of Carbon ion radiotherapy (RT) for patients with skull base chordoma is analyzed. Materials and Methods: Primary treatment costs and costs for recurrent tumors are estimated. The costs for treatment of recurrent tumors were estimated using a sample of 10 patients presenting with recurrent chordoma at the base of skull at DKFZ. Using various scenarios for the local control rate and reimbursements of Carbon ion therapy the cost-effectiveness of ion therapy for these tumors is analyzed. Results: If local control rate for skull base chordoma achieved with carbon ion therapy exceeds 70.3%, the overall treatment costs for carbon RT are lower than for conventional RTI. The cost-effectiveness ratio for carbon RT is 2539 Euro per 1% increase in survival, or 7692 Euro per additional life year. Conclusion: Current results support the thesis that Carbon ion RT, although more expensive, is at least as cost-effective as advanced photon therapies for these patients. Ion RT, however, offers substantial benefits for the patients such as improved control rates and less severe side effects

The ways of improvement of combination therapy results in patients with local cervical cancer

International Nuclear Information System (INIS)

Shumilo, A.O.

2010-01-01

A new solutions of a scientific task of modern oncogynecology, improvement of the efficacy of treatment for local cervical cancer on the account of expansion of the indications to operative treatment is presented on the clinical material (275 patients with stage II-III CC). The use of the developed technique of multimodality therapy based on the split course of combination radiation therapy against a background of neoadjuvant chemotherapy allowed to convert in 49.6% of cases of immobile tumor process to an operable stage followed by uterus and adnexae removal while at the traditional combination radiotherapy the resectability index was 6.9%.

Localized Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiation Therapy: A Long-Term Outcome in 86 Patients With 104 Treated Eyes

Energy Technology Data Exchange (ETDEWEB)

Harada, Ken, E-mail: keharada@ncc.go.jp [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Murakami, Naoya; Kitaguchi, Mayuka; Sekii, Shuhei; Takahashi, Kana; Yoshio, Kotaro; Inaba, Koji; Morota, Madoka; Ito, Yoshinori; Sumi, Minako [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Suzuki, Shigenobu [Department of Ophthalmic Oncology, National Cancer Center Hospital, Tokyo (Japan); Tobinai, Kensei [Department of Hematologic Oncology, National Cancer Center Hospital, Tokyo (Japan); Uno, Takashi [Department of Radiology, Chiba University School of Medicine, Chiba (Japan); Itami, Jun [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan)

2014-03-01

Purpose: To evaluate the natural history, behavior of progression, prognostic factors, and treatment-related adverse effects of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML). Methods and Materials: Eighty-six patients with histologically proven stage I POAML treated with radiation therapy at National Cancer Center Hospital, Tokyo between 1990 and 2010 were retrospectively reviewed. The median age was 56 years (range, 18-85 years). The median dose administered was 30 Gy (range, 30-46 Gy). Seventy-seven patients (90%) were treated by radiation therapy alone. Results: The median follow-up duration was 9 years (range, 0.9-22 years). The 5- and 10-year overall survival (OS) rates were 97.6% and 93.5%, respectively, and no patients died of lymphoma. Patients with tumor sizes ≥4 cm showed a greater risk of contralateral relapse (P=.012). Six patients with contralateral relapse were seen and treated by radiation therapy alone, and all the lesions were controlled well, with follow-up times of 3 to 12 years. There was 1 case of local relapse after radiation therapy alone, and 3 cases of relapse occurred in a distant site. Cataracts developed in 36 of the 65 eyes treated without lens shielding and in 12 of the 39 patients with lens shielding (P=.037). Conclusions: The majority of patients with POAML showed behavior consistent with that of localized, indolent diseases. Thirty gray of local irradiation seems to be quite effective. The initial bilateral involvement and contralateral orbital relapses can be also controlled with radiation therapy alone. Lens shielding reduces the risk of cataract.

Localized Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiation Therapy: A Long-Term Outcome in 86 Patients With 104 Treated Eyes

International Nuclear Information System (INIS)

Harada, Ken; Murakami, Naoya; Kitaguchi, Mayuka; Sekii, Shuhei; Takahashi, Kana; Yoshio, Kotaro; Inaba, Koji; Morota, Madoka; Ito, Yoshinori; Sumi, Minako; Suzuki, Shigenobu; Tobinai, Kensei; Uno, Takashi; Itami, Jun

2014-01-01

Purpose: To evaluate the natural history, behavior of progression, prognostic factors, and treatment-related adverse effects of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML). Methods and Materials: Eighty-six patients with histologically proven stage I POAML treated with radiation therapy at National Cancer Center Hospital, Tokyo between 1990 and 2010 were retrospectively reviewed. The median age was 56 years (range, 18-85 years). The median dose administered was 30 Gy (range, 30-46 Gy). Seventy-seven patients (90%) were treated by radiation therapy alone. Results: The median follow-up duration was 9 years (range, 0.9-22 years). The 5- and 10-year overall survival (OS) rates were 97.6% and 93.5%, respectively, and no patients died of lymphoma. Patients with tumor sizes ≥4 cm showed a greater risk of contralateral relapse (P=.012). Six patients with contralateral relapse were seen and treated by radiation therapy alone, and all the lesions were controlled well, with follow-up times of 3 to 12 years. There was 1 case of local relapse after radiation therapy alone, and 3 cases of relapse occurred in a distant site. Cataracts developed in 36 of the 65 eyes treated without lens shielding and in 12 of the 39 patients with lens shielding (P=.037). Conclusions: The majority of patients with POAML showed behavior consistent with that of localized, indolent diseases. Thirty gray of local irradiation seems to be quite effective. The initial bilateral involvement and contralateral orbital relapses can be also controlled with radiation therapy alone. Lens shielding reduces the risk of cataract

Integration of a Radiosensitivity Molecular Signature Into the Assessment of Local Recurrence Risk in Breast Cancer

International Nuclear Information System (INIS)

Torres-Roca, Javier F.; Fulp, William J.; Caudell, Jimmy J.; Servant, Nicolas; Bollet, Marc A.; Vijver, Marc van de; Naghavi, Arash O.; Harris, Eleanor E.; Eschrich, Steven A.

2015-01-01

Purpose: Recently, we developed radiosensitivity (RSI), a clinically validated molecular signature that estimates tumor radiosensitivity. In the present study, we tested whether integrating RSI with the molecular subtype refines the classification of local recurrence (LR) risk in breast cancer. Methods and Materials: RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy that included whole-breast radiation therapy with or without a tumor bed boost (dose range 45-72 Gy). The follow-up period for patients without recurrence was 10 years. The clinical endpoint was LR-free survival. Results: Although RSI did not uniformly predict for LR across the entire cohort, combining RSI and the molecular subtype identified a subpopulation with an increased risk of LR: triple negative (TN) and radioresistant (reference TN-radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). TN patients who were RSI-sensitive/intermediate had LR rates similar to those of luminal (LUM) patients (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined RSI and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008). Conclusions: The combined molecular subtype–RSI identified a novel molecular subpopulation (TN and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of RSI and

Integration of a Radiosensitivity Molecular Signature Into the Assessment of Local Recurrence Risk in Breast Cancer

Energy Technology Data Exchange (ETDEWEB)

Torres-Roca, Javier F., E-mail: javier.torresroca@moffitt.org [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Department of Chemical Biology and Molecular Medicine, Moffitt Cancer Center, Tampa, Florida (United States); Fulp, William J. [Department of Bioinformatics, Moffitt Cancer Center, Tampa, Florida (United States); Department of Biostatistics, Moffitt Cancer Center, Tampa, Florida (United States); Caudell, Jimmy J. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Servant, Nicolas [Institut Curie, INSERM U900, Paris (France); Mines ParisTech, Paris (France); Bollet, Marc A. [Institut Curie, INSERM U900, Paris (France); Vijver, Marc van de [Netherlands Cancer Institute, Amsterdam (Netherlands); Naghavi, Arash O. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Harris, Eleanor E. [East Carolina University, Greensborough, North Carolina (United States); Eschrich, Steven A. [Department of Bioinformatics, Moffitt Cancer Center, Tampa, Florida (United States)

2015-11-01

Purpose: Recently, we developed radiosensitivity (RSI), a clinically validated molecular signature that estimates tumor radiosensitivity. In the present study, we tested whether integrating RSI with the molecular subtype refines the classification of local recurrence (LR) risk in breast cancer. Methods and Materials: RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy that included whole-breast radiation therapy with or without a tumor bed boost (dose range 45-72 Gy). The follow-up period for patients without recurrence was 10 years. The clinical endpoint was LR-free survival. Results: Although RSI did not uniformly predict for LR across the entire cohort, combining RSI and the molecular subtype identified a subpopulation with an increased risk of LR: triple negative (TN) and radioresistant (reference TN-radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). TN patients who were RSI-sensitive/intermediate had LR rates similar to those of luminal (LUM) patients (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined RSI and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008). Conclusions: The combined molecular subtype–RSI identified a novel molecular subpopulation (TN and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of RSI and

Doing It Collaboratively! Addressing the Dilemmas of Designing Quantitative Effect Studies on Narrative Family Therapy in a Local Clinical Context

DEFF Research Database (Denmark)

Ejbye-Ernst, Ditte; Jørring, Nina Tejs

2017-01-01

suggest that involving narrative clinicians and clients in the development of a research design in the local clinical context might be helpful in overcoming narrative skepticism and criticism towards quantitative effect research. It is our hope that this article will inspire more narrative therapists...... in a local clinical context. The article offers a detailed case description of implementing psychometric effect measurements on narrative family therapy and of creating a shared collaborative stance for researchers using quantitative effect measurements and clinicians using narrative therapy. Our findings......This article suggests an approach for addressing the dilemmas narrative therapists face, wanting to make narrative therapy accessible to people seeking help in contexts favoring evidence-based therapy. The approach is inspired by participatory action research and involves clinicians and clients...

Evaluation of Delivery Costs for External Beam Radiation Therapy and Brachytherapy for Locally Advanced Cervical Cancer Using Time-Driven Activity-Based Costing.

Science.gov (United States)

Bauer-Nilsen, Kristine; Hill, Colin; Trifiletti, Daniel M; Libby, Bruce; Lash, Donna H; Lain, Melody; Christodoulou, Deborah; Hodge, Constance; Showalter, Timothy N

2018-01-01

To evaluate the delivery costs, using time-driven activity-based costing, and reimbursement for definitive radiation therapy for locally advanced cervical cancer. Process maps were created to represent each step of the radiation treatment process and included personnel, equipment, and consumable supplies used to deliver care. Personnel were interviewed to estimate time involved to deliver care. Salary data, equipment purchasing information, and facilities costs were also obtained. We defined the capacity cost rate (CCR) for each resource and then calculated the total cost of patient care according to CCR and time for each resource. Costs were compared with 2016 Medicare reimbursement and relative value units (RVUs). The total cost of radiation therapy for cervical cancer was $12,861.68, with personnel costs constituting 49.8%. Brachytherapy cost $8610.68 (66.9% of total) and consumed 423 minutes of attending radiation oncologist time (80.0% of total). External beam radiation therapy cost $4055.01 (31.5% of total). Personnel costs were higher for brachytherapy than for the sum of simulation and external beam radiation therapy delivery ($4798.73 vs $1404.72). A full radiation therapy course provides radiation oncologists 149.77 RVUs with intensity modulated radiation therapy or 135.90 RVUs with 3-dimensional conformal radiation therapy, with total reimbursement of $23,321.71 and $16,071.90, respectively. Attending time per RVU is approximately 4-fold higher for brachytherapy (5.68 minutes) than 3-dimensional conformal radiation therapy (1.63 minutes) or intensity modulated radiation therapy (1.32 minutes). Time-driven activity-based costing was used to calculate the total cost of definitive radiation therapy for cervical cancer, revealing that brachytherapy delivery and personnel resources constituted the majority of costs. However, current reimbursement policy does not reflect the increased attending physician effort and delivery costs of brachytherapy. We

Risk factors and therapy for goat mastitis in a hospital-based case-control study in Bangladesh.

Science.gov (United States)

Koop, Gerrit; Islam, Md Nurul; Rahman, Md Mizanur; Khatun, Momena; Ferdous, Jinnat; Sayeed, Md Abu; Islam, Shariful; Ahaduzzaman, Md; Akter, Sazeda; Mannan, Abdul; Hassan, Mohammad Mahmudul; Dissanayake, Ravi; Hoque, Md Ahasanul

2016-02-01

Bangladesh has a large population of goats, which contribute to the income, nutrition and welfare of the households of many families. Mastitis in goats has a low incidence, but is often very severe, making veterinary care necessary. The aim of this study was to identify seasonality and risk factors for goat mastitis in a hospital-based matched case-control study in a teaching veterinary hospital in Chittagong, Bangladesh and to describe the range of antimicrobial treatments applied in this situation. Cases of mastitis and controls were drawn from the hospital patient recording system, along with their risk factor status. Multiple imputation was applied to deal with the missing values in the data analysis. Mastitis occurred somewhat more in the rainy season, and comprised about 3% of all goats admitted to the hospital during January 2011-June 2014. Free-ranging farming system, poor body condition score and non-native goat breeds were significantly associated with case status. Treatment of clinical mastitis was variable and unsystematic, but the use of gentamicin was commonly recorded. The need for more prudent and evidence-based antimicrobial therapies is discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

The Very High Risk Prostate Cancer – a Contemporary Update

Science.gov (United States)

Mano, Roy; Eastham, James; Yossepowitch, Ofer

2017-01-01

Background Treatment of high-risk prostate cancer has evolved considerably over the past two decades, yet patients with very high-risk features may still experience poor outcome despite aggressive therapy. We review the contemporary literature focusing on current definitions, role of modern imaging and treatment alternatives in very high-risk prostate cancer. Methods We searched the MEDLINE database for all clinical trials or practice guidelines published in English between 2000 – 2016 with the following search terms: ‘prostatic neoplasms’ (MeSH Terms) AND (‘high risk’ (keyword) OR ‘locally advanced’ (keyword) OR ‘node positive’ (keyword)). Abstracts pertaining to very high-risk prostate cancer were evaluated and 40 pertinent studies served as the basis for this review. Results The term ‘very’ high-risk prostate cancer remains ill defined. The EAU and NCCN guidelines provide the only available definitions, categorizing those with clinical stage T3-4 or minimal nodal involvement as very-high risk irrespective of PSA level or biopsy Gleason score. Modern imaging with mpMRI and PET-PSMA scans plays a role in pretreatment assessment. Local definitive therapy by external beam radiation combined with androgen deprivation is supported by several randomized clinical trials whereas the role of surgery in the very high-risk setting combined with adjuvant radiation/ androgen deprivation therapy is emerging. Growing evidence suggest neoadjuvant taxane based chemotherapy in the context of a multimodal approach may be beneficial. Conclusions Men with very high-risk tumors may benefit from local definitive treatment in the setting of a multimodal regimen, offering local control and possibly cure in well selected patients. Further studies are necessary to better characterize the ‘very’ high-risk category and determine the optimal therapy for the individual patient. PMID:27618950

Modelling local government unit credit risk in the Republic of Croatia

Directory of Open Access Journals (Sweden)

Petra Posedel

2012-12-01

Full Text Available The objective of this paper is to determine possible indicators that affect local unit credit risk and investigate their effect on default (credit risk of local government units in Croatia. No system for the estimation of local unit credit risk has been established in Croatia so far causing many practical problems in local unit borrowing. Because of the specific nature of the operations of local government units and legislation that does not allow local government units to go into bankruptcy, conventional methods for estimating credit risk are not applicable, and the set of standard potential determinants of credit risk has to be expanded with new indicators. Thus in the paper, in addition to the usual determinants of credit risk, the hypothesis of the influence of political factors on local unit credit risk in Croatia is also tested out, with the use of a Tobit model. Results of econometric analysis show that credit risk of local government units in Croatia is affected by the political structure of local government, the proportion of income tax and surtax in operating revenue, the ratio of net operating balance, net financial liabilities and direct debt to operating revenue, as well as the ratio of debt repayment and cash, and direct debt and operating revenue.

Stereotactic body radiation therapy for reirradiation of localized adenocarcinoma of the pancreas

Directory of Open Access Journals (Sweden)

Lominska Chris E

2012-05-01

Full Text Available Abstract Background Local control rates are poor in the treatment of pancreatic cancer. We investigated the role of hypofractionated stereotactic body radiation therapy (SBRT for salvage or boost treatment after conventional doses of external beam radiation therapy. Methods All patients treated with SBRT for pancreatic adenocarcinoma at Georgetown University from June 2002 through July 2007 were examined. Eligible patients had prior external beam radiation therapy to the pancreas. Treatment parameters and clinical and radiographic follow-up were evaluated. Results Twenty-eight patients were identified who received SBRT after a median prior external beam radiotherapy dose of 50.4 Gy. The median patient age was 63 years old and the median follow-up was 5.9 months. Twelve of fourteen (85.7% evaluable patients were free from local progression, with three partial responses and nine patients with stable disease. Toxicity consisted of one case of acute Grade II nausea/vomiting, and two cases of Grade III late GI toxicity. The median overall survival was 5.9 months, with 18% survival and 70% freedom from local progression at one year. Conclusions Hypofractionated SBRT reirradiation of localized pancreatic cancer is a well-tolerated treatment. Most patients are free from local progression, albeit with limited follow-up, but overall survival remains poor.

Effects of Incretin-Based Therapies and SGLT2 Inhibitors on Skeletal Health.

Science.gov (United States)

Egger, Andrea; Kraenzlin, Marius E; Meier, Christian

2016-12-01

Anti-diabetic drugs are widely used and are essential for adequate glycemic control in patients with type 2 diabetes. Recently, marketed anti-diabetic drugs include incretin-based therapies (GLP-1 receptor agonists and DPP-4 inhibitors) and sodium-glucose co-transporter 2 (SGLT2) inhibitors. In contrast to well-known detrimental effects of thiazolidinediones on bone metabolism and fracture risk, clinical data on the safety of incretin-based therapies is limited. Based on meta-analyses of trials investigating the glycemic-lowering effect of GLP-1 receptor agonists and DPP4 inhibitors, it seems that incretin-based therapies are not associated with an increase in fracture risk. Sodium-glucose co-transporter 2 inhibitors may alter calcium and phosphate homeostasis as a result of secondary hyperparathyroidism induced by increased phosphate reabsorption. Although these changes may suggest detrimental effects of SGLT-2 inhibitors on skeletal integrity, treatment-related direct effects on bone metabolism seem unlikely. Observed changes in BMD, however, seem to result from increased bone turnover in the early phase of drug-induced weight loss. Fracture risk, which is observed in older patients with impaired renal function and elevated cardiovascular disease risk treated with SGLT2 inhibitors, seems to be independent of direct effects on bone but more likely to be associated with falls and changes in hydration status secondary to osmotic diuresis.

Outcomes for Spine Stereotactic Body Radiation Therapy and an Analysis of Predictors of Local Recurrence

International Nuclear Information System (INIS)

Bishop, Andrew J.; Tao, Randa; Rebueno, Neal C.; Christensen, Eva N.; Allen, Pamela K.; Wang, Xin A.; Amini, Behrang; Tannir, Nizar M.; Tatsui, Claudio E.; Rhines, Laurence D.; Li, Jing; Chang, Eric L.; Brown, Paul D.; Ghia, Amol J.

2015-01-01

Purpose: To investigate local control, survival outcomes, and predictors of local relapse for patients treated with spine stereotactic body radiation therapy. Methods and Materials: We reviewed the records of 332 spinal metastases consecutively treated with stereotactic body radiation therapy between 2002 and 2012. The median follow-up for all living patients was 33 months (range, 0-111 months). Endpoints were overall survival and local control (LC); recurrences were classified as either in-field or marginal. Results: The 1-year actuarial LC and overall survival rates were 88% and 64%, respectively. Patients with local relapses had poorer dosimetric coverage of the gross tumor volume (GTV) compared with patients without recurrence (minimum dose [Dmin] biologically equivalent dose [BED] 23.9 vs 35.1 Gy, P<.001; D98 BED 41.8 vs 48.1 Gy, P=.001; D95 BED 47.2 vs 50.5 Gy, P=.004). Furthermore, patients with marginal recurrences had poorer prescription coverage of the GTV (86% vs 93%, P=.01) compared with those with in-field recurrences, potentially because of more upfront spinal canal disease (78% vs 24%, P=.001). Using a Cox regression univariate analysis, patients with a GTV BED Dmin ≥33.4 Gy (median dose) (equivalent to 14 Gy in 1 fraction) had a significantly higher 1-year LC rate (94% vs 80%, P=.001) compared with patients with a lower GTV BED Dmin; this factor was the only significant variable on multivariate Cox analysis associated with LC (P=.001, hazard ratio 0.29, 95% confidence interval 0.14-0.60) and also was the only variable significant in a separate competing risk multivariate model (P=.001, hazard ratio 0.30, 95% confidence interval 0.15-0.62). Conclusions: Stereotactic body radiation therapy offers durable control for spinal metastases, but there is a subset of patients that recur locally. Patients with local relapse had significantly poorer tumor coverage, which was likely attributable to treatment planning directives that prioritized the

Outcomes for Spine Stereotactic Body Radiation Therapy and an Analysis of Predictors of Local Recurrence

Energy Technology Data Exchange (ETDEWEB)

Bishop, Andrew J.; Tao, Randa [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rebueno, Neal C. [Department of Radiation Dosimetry, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Christensen, Eva N.; Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang, Xin A. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Amini, Behrang [Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tannir, Nizar M. [Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tatsui, Claudio E.; Rhines, Laurence D. [Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Li, Jing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Eric L. [Department of Radiation Oncology, USC Norris Cancer Hospital, Keck School of Medicine of USC, Los Angeles, California (United States); Brown, Paul D. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ghia, Amol J., E-mail: ajghia@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2015-08-01

Purpose: To investigate local control, survival outcomes, and predictors of local relapse for patients treated with spine stereotactic body radiation therapy. Methods and Materials: We reviewed the records of 332 spinal metastases consecutively treated with stereotactic body radiation therapy between 2002 and 2012. The median follow-up for all living patients was 33 months (range, 0-111 months). Endpoints were overall survival and local control (LC); recurrences were classified as either in-field or marginal. Results: The 1-year actuarial LC and overall survival rates were 88% and 64%, respectively. Patients with local relapses had poorer dosimetric coverage of the gross tumor volume (GTV) compared with patients without recurrence (minimum dose [Dmin] biologically equivalent dose [BED] 23.9 vs 35.1 Gy, P<.001; D98 BED 41.8 vs 48.1 Gy, P=.001; D95 BED 47.2 vs 50.5 Gy, P=.004). Furthermore, patients with marginal recurrences had poorer prescription coverage of the GTV (86% vs 93%, P=.01) compared with those with in-field recurrences, potentially because of more upfront spinal canal disease (78% vs 24%, P=.001). Using a Cox regression univariate analysis, patients with a GTV BED Dmin ≥33.4 Gy (median dose) (equivalent to 14 Gy in 1 fraction) had a significantly higher 1-year LC rate (94% vs 80%, P=.001) compared with patients with a lower GTV BED Dmin; this factor was the only significant variable on multivariate Cox analysis associated with LC (P=.001, hazard ratio 0.29, 95% confidence interval 0.14-0.60) and also was the only variable significant in a separate competing risk multivariate model (P=.001, hazard ratio 0.30, 95% confidence interval 0.15-0.62). Conclusions: Stereotactic body radiation therapy offers durable control for spinal metastases, but there is a subset of patients that recur locally. Patients with local relapse had significantly poorer tumor coverage, which was likely attributable to treatment planning directives that prioritized the

Sexual function with localized prostate cancer: active surveillance vs radical therapy

NARCIS (Netherlands)

van den Bergh, Roderick C. N.; Korfage, Ida J.; Roobol, Monique J.; Bangma, Chris H.; de Koning, Harry J.; Steyerberg, Ewout W.; Essink-Bot, Marie-Louise

2012-01-01

OBJECTIVE To compare sexual function of men with localized prostate cancer (PCa) on active surveillance (AS) with similar patients who received radical therapy. PATIENTS AND METHODS Two groups of men with screening-detected localized PCa were compared. The first were men on AS within the prospective

Physical therapy approaches to reduce fall and fracture risk among older adults.

Science.gov (United States)

Karinkanta, Saija; Piirtola, Maarit; Sievänen, Harri; Uusi-Rasi, Kirsti; Kannus, Pekka

2010-07-01

Falls and fall-related injuries, such as fractures, are a growing problem among older adults, often causing longstanding pain, functional impairments, reduced quality of life and excess health-care costs and mortality. These problems have led to a variety of single component or multicomponent intervention strategies to prevent falls and subsequent injuries. The most effective physical therapy approach for the prevention of falls and fractures in community-dwelling older adults is regular multicomponent exercise; a combination of balance and strength training has shown the most success. Home-hazard assessment and modification, as well as assistive devices, such as canes and walkers, might be useful for older people at a high risk of falls. Hip protectors are effective in nursing home residents and potentially among other high-risk individuals. In addition, use of anti-slip shoe devices in icy conditions seems beneficial for older people walking outdoors. To be effective, multifactorial preventive programs should include an exercise component accompanied by individually tailored measures focused on high-risk populations. In this Review, we focus on evidence-based physical therapy approaches, including exercise, vibration training and improvements of safety at home and during periods of mobility. Additionally, the benefits of multifaceted interventions, which include risk factor assessment, dietary supplements, elements of physical therapy and exercise, are addressed.

Risk of Stroke with Various Types of Menopausal Hormone Therapies

DEFF Research Database (Denmark)

Løkkegaard, Ellen; Nielsen, Lars Hougaard; Keiding, Niels

2017-01-01

Background and Purpose: Double-blind randomized studies on the effects of oral postmenopausal hormone therapies were stopped mainly because of increased risk of stroke. We aimed to assess the risk of all strokes and various subtypes associated with hormone therapy and explore the influence of reg...

Local Progression among Men with Conservatively Treated Localized Prostate Cancer: Results from the Transatlantic Prostate Group

Science.gov (United States)

Eastham, James A.; Kattan, Michael W.; Fearn, Paul; Fisher, Gabrielle; Berney, Daniel M.; Oliver, Tim; Foster, Christopher S.; Møller, Henrik; Reuter, Victor; Cuzick, Jack; Scardino, Peter

2009-01-01

Objectives Men with clinically detected localized prostate cancer treated without curative intent are at risk of complications from local tumor growth. We investigated rates of local progression and need for local therapy among such men. Methods Men diagnosed with prostate cancer during 1990–1996 were identified from cancer registries throughout the United Kingdom. Inclusion criteria were age ≤76 yr at diagnosis, PSA level ≤100 ng/ml, and, within 6 mo after diagnosis, no radiation therapy, radical prostatectomy, evidence of metastatic disease, or death. Local progression was defined as increase in clinical stage from T1/2 to T3/T4 disease, T3 to T4 disease, and/or need for transurethral resection of the prostate (TURP) to relieve symptoms >6 mo after cancer diagnosis. Results The study included 2333 men with median follow-up of 85 mo (range: 6–174). Diagnosis was by TURP in 1255 men (54%), needle biopsy in 1039 (45%), and unspecified in 39 (2%). Only 29% were treated with hormonal therapy within 6 mo of diagnosis. Local progression occurred in 335 men, including 212 undergoing TURP. Factors most predictive of local progression on multivariable analysis were PSA at diagnosis and Gleason score of the diagnostic tissue (detrimental), and early hormonal therapy (protective). We present a nomogram that predicts the likelihood of local progression within 120 mo after diagnosis. Conclusions Men with clinically detected localized prostate cancer managed without curative intent have an approximately 15% risk for local progression within 10 yr of diagnosis. Among those with progression, the need for treatment is common, even among men diagnosed by TURP. When counseling men who are candidates for management without curative intent, the likelihood of symptoms from local progression must be considered. PMID:17544572

Credit networks and systemic risk of Chinese local financing platforms: Too central or too big to fail?. -based on different credit correlations using hierarchical methods

Science.gov (United States)

He, Fang; Chen, Xi

2016-11-01

The accelerating accumulation and risk concentration of Chinese local financing platforms debts have attracted wide attention throughout the world. Due to the network of financial exposures among institutions, the failure of several platforms or regions of systemic importance will probably trigger systemic risk and destabilize the financial system. However, the complex network of credit relationships in Chinese local financing platforms at the state level remains unknown. To fill this gap, we presented the first complex networks and hierarchical cluster analysis of the credit market of Chinese local financing platforms using the ;bottom up; method from firm-level data. Based on balance-sheet channel, we analyzed the topology and taxonomy by applying the analysis paradigm of subdominant ultra-metric space to an empirical data in 2013. It is remarked that we chose to extract the network of co-financed financing platforms in order to evaluate the effect of risk contagion from platforms to bank system. We used the new credit similarity measure by combining the factor of connectivity and size, to extract minimal spanning trees (MSTs) and hierarchical trees (HTs). We found that: (1) the degree distributions of credit correlation backbone structure of Chinese local financing platforms are fat tailed, and the structure is unstable with respect to targeted failures; (2) the backbone is highly hierarchical, and largely explained by the geographic region; (3) the credit correlation backbone structure based on connectivity and size is significantly heterogeneous; (4) key platforms and regions of systemic importance, and contagion path of systemic risk are obtained, which are contributed to preventing systemic risk and regional risk of Chinese local financing platforms and preserving financial stability under the framework of macro prudential supervision. Our approach of credit similarity measure provides a means of recognizing ;systemically important; institutions and regions

Targeted therapy for localized non-small-cell lung cancer: a review

Directory of Open Access Journals (Sweden)

Paleiron N

2016-07-01

Full Text Available Nicolas Paleiron,1 Olivier Bylicki,2 Michel André,1 Emilie Rivière,1 Frederic Grassin,1 Gilles Robinet,3 Christos Chouaïd4 On behalf of the GFPC Group 1Chest Department, HIA Clermont Tonnerre, Brest, 2Chest Department, HIA Percy, Clamart, 3Chest Department, CHU de Brest, Brest, 4GRC OncoEst, Université Paris XII, Paris, France Abstract: Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NSCLC, but their efficacy in localized NSCLC is less well established. The aim of this review is to analyze trials of targeted therapies in localized NSCLC. In patients with wild-type EGFR, tyrosine kinase inhibitors have shown no efficacy in Phase III trials. Few data are available for EGFR-mutated localized NSCLC, as routine biological profiling is not recommended. Available studies are small, often retrospectives, and/or conducted in a single-center making it difficult to draw firm conclusions. Ongoing prospective Phase III trials are comparing adjuvant tyrosine kinase inhibitor administration versus adjuvant chemotherapy. By analogy with the indication of bevacizumab in advanced NSCLC, use of antiangiogenic agents in the perioperative setting is currently restricted to nonsquamous NSCLC. Several trials of adjuvant or neoadjuvant bevacizumab are planned or ongoing, but for the moment there is no evidence of efficacy. Data on perioperative use of biomarkers in early-stage NSCLC come mainly from small, retrospective, uncontrolled studies. Assessment of customized adjuvant or neoadjuvant therapy in localized NSCLC (with or without oncogenic driver mutations is a major challenge. Keywords: targeted therapy, non-small-cell lung cancer, adjuvant, neo-adjuvant, surgery 

Assessment of radiation-induced second cancer risks in proton therapy and IMRT for organs inside the primary radiation field

Science.gov (United States)

Paganetti, Harald; Athar, Basit S.; Moteabbed, Maryam; Adams, Judith A.; Schneider, Uwe; Yock, Torunn I.

2012-10-01

There is clinical evidence that second malignancies in radiation therapy occur mainly within the beam path, i.e. in the medium or high-dose region. The purpose of this study was to assess the risk for developing a radiation-induced tumor within the treated volume and to compare this risk for proton therapy and intensity-modulated photon therapy (IMRT). Instead of using data for specific patients we have created a representative scenario. Fully contoured age- and gender-specific whole body phantoms (4 year and 14 year old) were uploaded into a treatment planning system and tumor volumes were contoured based on patients treated for optic glioma and vertebral body Ewing's sarcoma. Treatment plans for IMRT and proton therapy treatments were generated. Lifetime attributable risks (LARs) for developing a second malignancy were calculated using a risk model considering cell kill, mutation, repopulation, as well as inhomogeneous organ doses. For standard fractionation schemes, the LAR for developing a second malignancy from radiation therapy alone was found to be up to 2.7% for a 4 year old optic glioma patient treated with IMRT considering a soft-tissue carcinoma risk model only. Sarcoma risks were found to be below 1% in all cases. For a 14 year old, risks were found to be about a factor of 2 lower. For Ewing's sarcoma cases the risks based on a sarcoma model were typically higher than the carcinoma risks, i.e. LAR up to 1.3% for soft-tissue sarcoma. In all cases, the risk from proton therapy turned out to be lower by at least a factor of 2 and up to a factor of 10. This is mainly due to lower total energy deposited in the patient when using proton beams. However, the comparison of a three-field and four-field proton plan also shows that the distribution of the dose, i.e. the particular treatment plan, plays a role. When using different fractionation schemes, the estimated risks roughly scale with the total dose difference in%. In conclusion, proton therapy can

Empiric antibiotic therapy in urinary tract infection in patients with risk factors for antibiotic resistance in a German emergency department.

Science.gov (United States)

Bischoff, Sebastian; Walter, Thomas; Gerigk, Marlis; Ebert, Matthias; Vogelmann, Roger

2018-01-26

is an equal or better choice compared to fluoroquinolones, cephalosporins or gentamicin. This study highlights the importance of monitoring local resistance rates and its risk factors in order to improve empiric therapy in a local environment.

Local knowledge: Empirical Fact to Develop Community Based Disaster Risk Management Concept for Community Resilience at Mangkang Kulon Village, Semarang City

Science.gov (United States)

Kapiarsa, A. B.; Sariffuddin, S.

2018-02-01

Local knowledge in disaster management should not be neglected in developing community resilience. The circular relation between humans and their living habitat and community social relation have developed the local knowledge namely specialized knowledge, shared knowledge, and common knowledge. Its correlation with community-based disaster management has become an important discussion specially to answer can local knowledge underlie community-based disaster risk reduction concept development? To answer this question, this research used mix-method. Interview and crosstab method for 73 respondents with 90% trust rate were used to determine the correlation between local knowledge and community characteristics. This research found out that shared knowledge dominated community local knowledge (77%). While common knowledge and specialized knowledge were sequentially 8% and 15%. The high score of shared value (77%) indicated that local knowledge was occurred in household level and not yet indicated in community level. Shared knowledge was found in 3 phases of the resilient community in dealing with disaster, namely mitigation, emergency response, and recovery phase. This research, therefore, has opened a new scientific discussion on the self-help concept in community-help concept in CBDRM concept development in Indonesia.

Stereotactic body radiation therapy planning with duodenal sparing using volumetric-modulated arc therapy vs intensity-modulated radiation therapy in locally advanced pancreatic cancer: A dosimetric analysis

Energy Technology Data Exchange (ETDEWEB)

Kumar, Rachit; Wild, Aaron T.; Ziegler, Mark A.; Hooker, Ted K.; Dah, Samson D.; Tran, Phuoc T.; Kang, Jun; Smith, Koren; Zeng, Jing [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 401N. Broadway, Weinberg Suite 1440, Baltimore, MD 21231 (United States); Pawlik, Timothy M. [Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Tryggestad, Erik [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 401N. Broadway, Weinberg Suite 1440, Baltimore, MD 21231 (United States); Ford, Eric [Department of Radiation Oncology, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA (United States); Herman, Joseph M., E-mail: jherma15@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 401N. Broadway, Weinberg Suite 1440, Baltimore, MD 21231 (United States)

2013-10-01

Stereotactic body radiation therapy (SBRT) achieves excellent local control for locally advanced pancreatic cancer (LAPC), but may increase late duodenal toxicity. Volumetric-modulated arc therapy (VMAT) delivers intensity-modulated radiation therapy (IMRT) with a rotating gantry rather than multiple fixed beams. This study dosimetrically evaluates the feasibility of implementing duodenal constraints for SBRT using VMAT vs IMRT. Non–duodenal sparing (NS) and duodenal-sparing (DS) VMAT and IMRT plans delivering 25 Gy in 1 fraction were generated for 15 patients with LAPC. DS plans were constrained to duodenal D{sub max} of<30 Gy at any point. VMAT used 1 360° coplanar arc with 4° spacing between control points, whereas IMRT used 9 coplanar beams with fixed gantry positions at 40° angles. Dosimetric parameters for target volumes and organs at risk were compared for DS planning vs NS planning and VMAT vs IMRT using paired-sample Wilcoxon signed rank tests. Both DS VMAT and DS IMRT achieved significantly reduced duodenal D{sub mean}, D{sub max}, D{sub 1cc}, D{sub 4%}, and V{sub 20} {sub Gy} compared with NS plans (all p≤0.002). DS constraints compromised target coverage for IMRT as demonstrated by reduced V{sub 95%} (p = 0.01) and D{sub mean} (p = 0.02), but not for VMAT. DS constraints resulted in increased dose to right kidney, spinal cord, stomach, and liver for VMAT. Direct comparison of DS VMAT and DS IMRT revealed that VMAT was superior in sparing the left kidney (p<0.001) and the spinal cord (p<0.001), whereas IMRT was superior in sparing the stomach (p = 0.05) and the liver (p = 0.003). DS VMAT required 21% fewer monitor units (p<0.001) and delivered treatment 2.4 minutes faster (p<0.001) than DS IMRT. Implementing DS constraints during SBRT planning for LAPC can significantly reduce duodenal point or volumetric dose parameters for both VMAT and IMRT. The primary consequence of implementing DS constraints for VMAT is increased dose to other organs at

Hormonal therapy and risk of breast cancer in mexican women.

Directory of Open Access Journals (Sweden)

Amina Amadou

Full Text Available The use of hormonal therapies, including hormonal contraceptives (HC and postmenopausal hormone replacement therapy (HRT have been shown to influence breast cancer (BC risk. However, the variations of these effects among populations and ethnic groups are not completely documented, especially among Hispanic women. We evaluated the association between HC and premenopausal BC risk, and between HRT and postmenopausal BC risk in Mexican women. Data from a Mexican multi-center population-based case-control study ofwomen aged 35 to 69 years were analysed. A total of 1000 cases and 1074 matched controls were recruited between 2004 and 2007. Information on hormonal therapy was collected through a structured questionnaire. Results were analysed using conditional logistic regression models. Overall, HC were used by 422/891 (47.3% premenopausal women and HRT was used by 220/1117 (19.7% postmenopausal women. For HC, odds ratios (ORs for BC were 1.11 (95% confidence interval (CI: 0.82, 1.49 for current users and 1.68 (95% CI: 0.67, 4.21 for ever-users. No clear effect of duration of use was observed. For HRT, the OR for BC was significantly increased in ever users (OR: 1.45; 95% CI: 1.01, 2.08. A non-significant increased risk was observed for combined estrogen/progestin, (OR =  1.85; 95% CI: 0.84, 4.07 whereas no effect was observed for the use of estrogen alone (OR = 1.14; 95% CI: 0.68, 1.91. Our results indicate that, HC had a non-significant effect on the risk of pre-menopausal BC, but suggested that injected contraceptives may slightly increase the risk, whereas HRT had a significant effect on post-menopausal BC in this population. This study provides new information about the effects of HC and HRT on BC risk in a Mexican population, which may be of relevance for the population of Latin America as a whole.

Evidence-based practice in women's health: hormone therapy for women at menopause.

Science.gov (United States)

Rousseau, M E

2001-01-01

Women's health providers, especially midwives, must take into account the known benefits and risks, as well as the "unknown," when recommending the use of hormone therapy for menopausal women, especially as it relates to heart disease, breast cancer, impaired cognition, and osteoporosis. The most recent evidence available from various studies about the benefits and risks of estrogen and hormone therapy at menopause suggests that, although hormone therapy may be protective in some women against heart disease and osteoporosis, evidence is less certain about the benefits of hormone protection against impaired cognition and the risks of breast cancer with use. The clinical approach used by midwives in which individualizing care based on each woman's health status history as well as preferences is highly appropriate for women in the perimenopausal and menopausal period.

Cf-252 neutron brachytherapy: an advance for bulky localized cancer therapy

International Nuclear Information System (INIS)

Maruyama, Y.

1984-01-01

The physical and radiobiogical basis as well as the rationale for neutron brachytherapy, using Cf-252, in human cancer therapy is reviewed. Cf-252 brachytherapy represents an economical and effective form of neutron radiotherapy that is readily and safely applied clinically. It can be used anywhere in the world without unusual personnel, equipment or facilities, or prohibitive expenses or maintenance costs. Used on bulky head and neck, thoracic, abdominal, pelvic, brain and appendage cancers, it overcomes hypoxic radioresistance and produces remarkable rates of tumor clearance. It is easily combined with photon radiotherapy and in proper schedules and doses, it can control advanced but still localized regional cancers to produce tumor cure. It will clear the local manifestations of recurrent or metastatic tumors or advanced stages of primary tumors and therefore in conjunction with other adjuvant therapies offers much more effective tumor control and palliation than present conventional therapy. (Auth.)

Radiotherapy and androgen ablation for clinically localized high-risk prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Pollack, Alan; Zagars, Gunar K; Kopplin, Susan

1995-04-30

Purpose: The response of patients with clinical stages T1-4 prostate cancer to radiotherapy is variable. A particularly poor prognostic group has been found to be comprised of those with pretreatment prostate specific antigen (PSA) levels above 30 ng/ml with any tumor grade, or PSA levels > 10 and {<=} 30 with tumors grade 3 or 4. These patients have over an 80% actuarial risk of biochemical failure 3 years after definitive external beam radiotherapy. Thus, patients with these high-risk features require more aggressive therapy. During the last 3-4 years, the policy to treat such patients with radiotherapy and androgen ablation (XRT/HORM) was instituted. A retrospective comparison was made between high-risk patients treated with radiotherapy alone (XRT) vs. XRT/HORM. Methods and Materials: Between 1987 and 1991, there were 81 high-risk patients treated with XRT. There were 38 high-risk patients treated with XRT/HORM between 1990 and 1992. The median follow-up was 37 months for the XRT group and 22 months for the XRT/HORM group. No patient had clinical, radiographic, or pathologic evidence of lymph node involvement. The median dose to the prostate was 66 Gy for the XRT group and 68 Gy for the XRT/HORM group. Results: The distributions of several potential prognostic factors were analyzed. Significant differences between the groups were observed for tumor grade, pretreatment prostatic acid phosphatase, and age. The XRT/HORM group was composed of patients with worse features, including a greater proportion of patients with grade 4 tumors, more with abnormal acid phosphatase levels, and more under 60 years of age. The actuarial incidence of a rising PSA at 3 years for the XRT group was 81% vs. 15% for the XRT/HORM group (p < 0.0001). In addition, local relapse at 3 years was 34% for the XRT group and 15% for the XRT/HORM group (p < 0.02). There was no difference between the groups in terms of survival. Cox proportional hazards analyses were performed using several

Evolution of nodule stiffness might predict response to local ablative therapy: A series of patients with hepatocellular carcinoma.

Directory of Open Access Journals (Sweden)

Michael Praktiknjo

Full Text Available Early information on treatment response of HCC to local ablative therapy is crucial. Elastography as a non-invasive method has recently been shown to play a potential role in distinguishing between benign and malignant liver lesions. Elastography of hepatocellular carcinoma (HCC in early response to local ablative therapy has not been studied to date.We prospectively included a cohort of 14 patients with diagnosis of HCC who were treated with local ablative therapy (transarterial chemoembolization, TACE and/or radiofrequency ablation, RFA. We used 2D shear-wave elastography (RT 2D-SWE to examine stiffness of HCC lesion before and 3, 30 and 90 days after local ablative therapy. Contrast-enhanced imaging after 90 days was performed to evaluate treatment response. Primary endpoint was stiffness of HCC in response to local ablative therapy. Secondary end point was tumor recurrence.Stiffness of HCC nodules and liver showed no significant difference prior to local ablative therapy. As early as three days after treatment, stiffness of responding HCC was significantly higher compared to non-responding. Higher stiffness before treatment was significantly associated with tumor recurrence.Nodule stiffness in general and RT 2D-SWE in particular could provide a useful tool for early prediction of HCC response to local ablative therapy.

The relationship between technical parameters of external beam radiation therapy and complications for localized prostate cancer

International Nuclear Information System (INIS)

Kitamura, Kei; Shirato, Hiroki; Suzuki, Keishiro

2000-01-01

This study was performed to review retrospectively the clinical course of chronic rectal bleeding as a complication of external beam radiation therapy for localized prostate cancer and to analyze the relationship between technical parameters of radiation therapy and the complications. Seventy-one patients with stages A2, B and C were treated with local-field radiotherapy (total dose 52.5-66 Gy, daily dose 2.0-3.28 Gy, field area 30-81 cm 2 , number of fields 3-15 ports, planning simulations X-ray or CT-based) between 1989 and 1998 at three institutions. The protocols were consistent during this same period at these institutions. Multivariate analysis revealed pretreatment PSA and Gleason sum to be statistically significant predictors of 5 year prostatic specific antigen (PSA) relapse-free rates in a median follow-up period of 42 months (range 12-119 months). The significant risk factors for higher grading of acute morbidity were a biological equivalent dose, α/β=10 (BED 10 ) ≥65 Gy, dose per fraction ≥3.0 Gy, field area ≥42 cm 2 , fewer ports and X-ray planning simulation. However, no parameter was associated with higher grading of late morbidity. Eleven patients (15.4%) experienced a late GI complication: grade 1 (4.2%), grade 2 (9.8%), grade 3 (1.4%). The median time to occurrence of rectal bleeding was 12 months after radiotherapy and the mean duration of morbidity was 11 months. Higher total dose and dose per fraction, larger field area, fewer ports and X-ray simulation increased the grades of acute morbidity. A majority of chronic rectal bleedings were transient and responded to conservative treatment. (author)

Incretin-based therapies and risk of pancreatic cancer in patients with type 2 diabetes: A meta-analysis of randomized controlled trials.

Science.gov (United States)

Wang, Haining; Liu, Ye; Tian, Qing; Yang, Jin; Lu, Ran; Zhan, Siyan; Haukka, Jari; Hong, Tianpei

2018-04-01

To perform a meta-analysis of randomized controlled trials (RCTs), including 6 recently published large-scale cardiovascular outcome trials (CVOTs), to evaluate the risk of pancreatic cancer with incretin-based therapies in patients with type 2 diabetes (T2DM). For the period January 1, 2007 to May 1, 2017, the PubMed, Embase, Cochrane Central Register and ClininalTrials.gov databases were searched for RCTs in people with T2DM that compared incretin drugs with placebo or other antidiabetic drugs, with treatment and follow-up durations of ≥52 weeks. Two reviewers screened the studies, extracted the data and assessed the risk of bias independently and in duplicate. A total of 33 studies (n = 79 971), including the 6 CVOTs, with 87 pancreatic cancer events were identified. Overall, the pancreatic cancer risk was not increased in patients administered incretin drugs compared with controls (Peto odds ratio [OR] 0.67, 95% confidence interval [CI] 0.44-1.02). In the 6 CVOTs, 79 pancreatic cancer events were identified in 55 248 participants. Pooled estimates of the 6 CVOTs showed an identical tendency (Peto OR 0.65, 95% CI 0.42-1.01). Notably, in the subgroup of participants who received treatment and follow-up for ≥104 weeks, 84 pancreatic cancer events were identified in 59 919 participants, and a lower risk of pancreatic cancer was associated with incretin-based therapies (Peto OR 0.62, 95% CI 0.41-0.95). Treatment with incretin drugs was not associated with an increased risk of pancreatic cancer in people with T2DM. Instead, it might protect against pancreatic malignancy in patients treated for ≥104 weeks. © 2017 John Wiley & Sons Ltd.

Multidisciplinary management of the locally advanced unresectable non-small cell lung cancer

International Nuclear Information System (INIS)

Cho, Kwan Ho

2004-01-01

Locally advanced (Stage III) non-small cell lung cancer (NSCLC) accounts for approximately one third of all cases of NSCLC. Few patients with locally advanced NSCLC present with disease amenable to curative surgical resection. Historically, these patients were treated with primary thoracic radiation therapy (RT) and had poor long term survival rates, due to both progression of local disease and development of distant metastases. Over the last two decades, the use of multidisciplinary approach has improved the outcome for patients with locally advanced NSCLC. Combined chemoradiotherapy is the most favored approach for treatment of locally advanced unresectable NSCLC. There are two basic treatment protocols for administering combined chemotherapy and radiation, sequential versus concurrent. The rationale for using chemotherapy is to eliminate subclinical metastatic disease while improving local control. Sequential use of chemotherapy followed by radiotherapy has improved median and long term survival compared to radiation therapy alone. This approach appears to decrease the risk of distant metastases, but local failure rates remain the same as radiation alone. Concurrent chemoradiotherapy has been studied extensively. The potential advantages of this approach may include sensitization of tumor cells to radiation by the administration of chemotherapy, and reduced overall treatment time compared to sequential therapy; which is known to be important for improving local control in radiation biology. This approach improves survival primarily as a result of improved local control. However, it doesn't seem to decrease the risk of distant metastases probably because concurrent chemoradiation requires dose reductions in chemotherapy due to increased risks of acute morbidity such as acute esophageal toxicity. Although multidisciplinary therapy has led to improved survival rates compared to radiation therapy alone and has become the new standard of care, the optimal therapy of

Model-based synthesis of locally contingent responses to global market signals

Science.gov (United States)

Magliocca, N. R.

2015-12-01

Rural livelihoods and the land systems on which they depend are increasingly influenced by distant markets through economic globalization. Place-based analyses of land and livelihood system sustainability must then consider both proximate and distant influences on local decision-making. Thus, advancing land change theory in the context of economic globalization calls for a systematic understanding of the general processes as well as local contingencies shaping local responses to global signals. Synthesis of insights from place-based case studies of land and livelihood change is a path forward for developing such systematic knowledge. This paper introduces a model-based synthesis approach to investigating the influence of local socio-environmental and agent-level factors in mediating land-use and livelihood responses to changing global market signals. A generalized agent-based modeling framework is applied to six case-study sites that differ in environmental conditions, market access and influence, and livelihood settings. The largest modeled land conversions and livelihood transitions to market-oriented production occurred in sties with relatively productive agricultural land and/or with limited livelihood options. Experimental shifts in the distributions of agents' risk tolerances generally acted to attenuate or amplify responses to changes in global market signals. Importantly, however, responses of agents at different points in the risk tolerance distribution varied widely, with the wealth gap growing wider between agents with higher or lower risk tolerance. These results demonstrate model-based synthesis is a promising approach to overcome many of the challenges of current synthesis methods in land change science, and to identify generalized as well as locally contingent responses to global market signals.

Improved Beam Angle Arrangement in Intensity Modulated Proton Therapy Treatment Planning for Localized Prostate Cancer

International Nuclear Information System (INIS)

Cao, Wenhua; Lim, Gino J.; Li, Yupeng; Zhu, X. Ronald; Zhang, Xiaodong

2015-01-01

Purpose: This study investigates potential gains of an improved beam angle arrangement compared to a conventional fixed gantry setup in intensity modulated proton therapy (IMPT) treatment for localized prostate cancer patients based on a proof of principle study. Materials and Methods: Three patients with localized prostate cancer retrospectively selected from our institution were studied. For each patient, IMPT plans were designed using two, three and four beam angles, respectively, obtained from a beam angle optimization algorithm. Those plans were then compared with ones using two lateral parallel-opposed beams according to the conventional planning protocol for localized prostate cancer adopted at our institution. Results: IMPT plans with two optimized angles achieved significant improvements in rectum sparing and moderate improvements in bladder sparing against those with two lateral angles. Plans with three optimized angles further improved rectum sparing significantly over those two-angle plans, whereas four-angle plans found no advantage over three-angle plans. A possible three-beam class solution for localized prostate patients was suggested and demonstrated with preserved dosimetric benefits because individually optimized three-angle solutions were found sharing a very similar pattern. Conclusions: This study has demonstrated the potential of using an improved beam angle arrangement to better exploit the theoretical dosimetric benefits of proton therapy and provided insights of selecting quality beam angles for localized prostate cancer treatment

Hormone replacement therapy and the risk of endometrial cancer

DEFF Research Database (Denmark)

Sjögren, Lea L; Mørch, Lina Steinrud; Løkkegaard, Ellen

2016-01-01

BACKGROUND: In 1975, estrogen only was found to be associated with an increased risk of endometrial cancer. In November 2015, NICE guidelines on hormone therapy were published that did not take this risk into account. AIM: This systematic literature review assesses the safety of estrogen plus...... progestin therapy according to the risk of endometrial cancer, while considering both regimen and type of progestin. METHODS: PubMed, EMBASE and the Cochrane Library were searched, resulting in the identification of 527 published articles on menopausal women with intact uteri treated with estrogen only......, estrogen plus progestin or tibolone for a minimum of one year. Risk of endometrial cancer was compared to placebo or never users and measured as relative risk, hazard or odds ratio. RESULTS: 28 studies were included. The observational literature found an increased risk among users of estrogen alone...

Stereotactic Body Radiation Therapy (SBRT) for clinically localized prostate cancer: the Georgetown University experience

International Nuclear Information System (INIS)

Chen, Leonard N; Lei, Siyuan; Batipps, Gerald P; Kowalczyk, Keith; Bandi, Gaurav

2013-01-01

Stereotactic body radiation therapy (SBRT) delivers fewer high-dose fractions of radiation which may be radiobiologically favorable to conventional low-dose fractions commonly used for prostate cancer radiotherapy. We report our early experience using SBRT for localized prostate cancer. Patients treated with SBRT from June 2008 to May 2010 at Georgetown University Hospital for localized prostate carcinoma, with or without the use of androgen deprivation therapy (ADT), were included in this retrospective review of data that was prospectively collected in an institutional database. Treatment was delivered using the CyberKnife® with doses of 35 Gy or 36.25 Gy in 5 fractions. Biochemical control was assessed using the Phoenix definition. Toxicities were recorded and scored using the CTCAE v.3. Quality of life was assessed before and after treatment using the Short Form-12 Health Survey (SF-12), the American Urological Association Symptom Score (AUA) and Sexual Health Inventory for Men (SHIM) questionnaires. Late urinary symptom flare was defined as an AUA score ≥ 15 with an increase of ≥ 5 points above baseline six months after the completion of SBRT. One hundred patients (37 low-, 55 intermediate- and 8 high-risk according to the D’Amico classification) at a median age of 69 years (range, 48–90 years) received SBRT, with 11 patients receiving ADT. The median pre-treatment prostate-specific antigen (PSA) was 6.2 ng/ml (range, 1.9-31.6 ng/ml) and the median follow-up was 2.3 years (range, 1.4-3.5 years). At 2 years, median PSA decreased to 0.49 ng/ml (range, 0.1-1.9 ng/ml). Benign PSA bounce occurred in 31% of patients. There was one biochemical failure in a high-risk patient, yielding a two-year actuarial biochemical relapse free survival of 99%. The 2-year actuarial incidence rates of GI and GU toxicity ≥ grade 2 were 1% and 31%, respectively. A median baseline AUA symptom score of 8 significantly increased to 11 at 1 month (p = 0.001), however returned to

Evidence - based medicine/practice in sports physical therapy.

Science.gov (United States)

Manske, Robert C; Lehecka, B J

2012-10-01

A push for the use of evidence-based medicine and evidence-based practice patterns has permeated most health care disciplines. The use of evidence-based practice in sports physical therapy may improve health care quality, reduce medical errors, help balance known benefits and risks, challenge views based on beliefs rather than evidence, and help to integrate patient preferences into decision-making. In this era of health care utilization sports physical therapists are expected to integrate clinical experience with conscientious, explicit, and judicious use of research evidence in order to make clearly informed decisions in order to help maximize and optimize patient well-being. One of the more common reasons for not using evidence in clinical practice is the perceived lack of skills and knowledge when searching for or appraising research. This clinical commentary was developed to educate the readership on what constitutes evidence-based practice, and strategies used to seek evidence in the daily clinical practice of sports physical therapy.

Radiotherapy and hormone therapy in intermediate risk prostate cancer: a critical review; Radioterapia e hormonioterapia no cancer de prostata de risco intermediario: uma revisao critica

Energy Technology Data Exchange (ETDEWEB)

Franco, Rejane Carolina, E-mail: rejanefranco@icloud.com [Hospital das Clinicas da Faculdade de Medicina de Sao Paulo, Sao Paulo, SP (Brazil); Souhami, Luis, E-mail: luis.souhami@mcgill.ca [Departamento de Radioterapia McGill University. Montreal, Quebec (Canada)

2015-04-15

Introduction: The standard treatment for patients with high risk prostate cancer is the combined use of radiation therapy (RT ) and hormone therapy (HT). In regards to patients stratified as intermediate risk, the use of HT associated with RT remains controversial, and its use should be carefully planned and based on available evidence. Objective: To critically assess results of randomized studies published in the literature that associated the use of HT of short duration with an average period of 6 months with RT in the treatment of patients with localized prostate cancer classified as intermediate risk. Method: Only randomized studies comparing these treatments were eligible for this review. A structured search through 'PubMed' was carried out using the terms 'androgen suppression therapy', 'radiotherapy', 'randomized trials', 'phase 3 trials', 'prostate cancer' and 'intermediate risk'. Results: Four randomized studies comparing RT alone to RT plus short course HT were found and selected. The majority of the trials had a mixed population of intermediate and high risk disease and did not include patients with only intermediate risk. Despite that, there appears to be a significant benefit for the combined approach regarding disease-free survival, biochemical free survival and overall survival. Conclusion: The randomized studies published so far suggest improved outcomes for the group of patients receiving RT and short course HT. Data from randomized trials comparing RT alone to RT and short course HT in patients with intermediate risk only are forthcoming. (author)

Risk perception of tsunami in the community of Arauco, Chile - a contribution of risk perception to disaster risk management at local level

Science.gov (United States)

Kubisch, M. Sc. Susanne; Edilia Jaque Castillo, Dra.; Braun, JProf. Andreas Ch., ,, Dr.

2017-04-01

The research was carried out in the city center of the coastal community of Arauco, Central Chile. The community of Arauco was one of the most affected communities of the tsunami in Chile, the 27th of February 2010. For the data evaluation, the affected inhabitants of the community have been surveyed via standardized questionnaires. Furthermore experts of different fields, amongst others, Disaster Risk Management (DRM), risk education, urban and regional planning, as well as geology have been consulted in form of expert interviews. The results revealed a high risk perception part of the affected community and a weakness of DRM especially at local level, which opens a gap between the evaluation and treatment of risk by experts and risk perception of the affected community. The risk perception of the affected community, here, is predominantly determined by ecological vulnerability, expressed in direct and indirect experience of a tsunami and by institutional vulnerability, expressed among others by a weakness of DRM at local level and a mistrust in responsible institutions for DRM. Due to the institutional vulnerability and the mistrust in responsible institutions we recommend a Community Based Approach (CBA) to strengthen DRM at local level and to take advantage of the high risk perception and knowledge of the affected community. Involving the community in DRM, we assume to close the gap between risk evaluation of experts and risk perception of the inhabitants and to come up with the unique necessities and conditions at local level. Especially in centralized countries, DRM is less effective, because at the one hand, decisions are made distant from the affected communities, so that measures often do not come up with the unique conditions and necessities at local level, and on the other hand measures often do not find acceptance by the affected community. Furthermore centralized DRM is often not effective and quick in response in case of emergency. Another obstacle

Trends in primary surgical and radiation therapy for localized breast cancer in the detroit metropolitan area 1973-1992

International Nuclear Information System (INIS)

Chuba, Paul J.; Simon, Michael S.

1997-01-01

Purpose: The purpose of this report is to describe trends in primary surgical and radiation therapy for localized breast cancer from 1973 through 1992 among residents of the Detroit Metropolitan area. Methods and Materials: Data on surgical and radiation therapy procedures for women with local stage breast cancer were obtained from the population-based Metropolitan Detroit Cancer Surveillance System (MDCSS). Results: Women age 75 years and older were treated less aggressively than younger women (< age 75) as evidenced by higher rates of simple mastectomy or no treatment among older women. Younger women (< age 75) were more likely to have had optimal breast conservation therapy which consisted of partial mastectomy, axillary lymph node dissection (ALND), and radiation therapy, than were women who were older than 75. Partial mastectomy has increased proportionally from 4% of all breast cancer surgeries in the time period 1973 to 1977, to 39% of all surgeries from 1988 through 1992. Conclusion: A marked difference in surgical treatment of breast cancer exists for younger vs. older women. Despite changes in surgical treatment trends for breast cancer, a large proportion of women who are candidates for conservative therapy continue to undergo mastectomy

[To the issue of local treatment in combination therapy of chronic urethritis, associated with sexually transmitted infections].

Science.gov (United States)

Abdrahmanov, R M; Fajzullina, E V; Abdrahmanov, A R; Haliullin, R R

2015-12-01

The article shows the high efficacy of the additional local use of the drug Miramistin in combination therapy of chronic urethritis, associated with sexually transmitted infections (STIs). In accordance with the principles of evidence-based medicine, patients were assigned to the study group (n=110) treated with conventional therapy and Miramistin, and the comparison group (n=40) treated with conventional therapy only. The between-group comparison of treatment effectiveness was carried out by matching results of the etiological healing, the changes of the endoscopic picture of the urethra, and basic clinical manifestations of STI: the degree of inflammatory reaction of urethral mucous membrane, dysuria, pain and sexual syndrome.

Surgical Margins and the Risk of Local-Regional Recurrence After Mastectomy Without Radiation Therapy

International Nuclear Information System (INIS)

Childs, Stephanie K.; Chen Yuhui; Duggan, Margaret M.; Golshan, Mehra; Pochebit, Stephen; Wong, Julia S.; Bellon, Jennifer R.

2012-01-01

Purpose: Although positive surgical margins are generally associated with a higher risk of local-regional recurrence (LRR) for most solid tumors, their significance after mastectomy remains unclear. We sought to clarify the influence of the mastectomy margin on the risk of LRR. Methods and Materials: The retrospective cohort consisted of 397 women who underwent mastectomy and no radiation for newly diagnosed invasive breast cancer from 1998-2005. Time to isolated LRR and time to distant metastasis (DM) were evaluated by use of cumulative-incidence analysis and competing-risks regression analysis. DM was considered a competing event for analysis of isolated LRR. Results: The median follow-up was 6.7 years (range, 0.5-12.8 years). The superficial margin was positive in 41 patients (10%) and close (≤2 mm) in 56 (14%). The deep margin was positive in 23 patients (6%) and close in 34 (9%). The 5-year LRR and DM rates for all patients were 2.4% (95% confidence interval, 0.9-4.0) and 3.5% (95% confidence interval, 1.6-5.3) respectively. Fourteen patients had an LRR. Margin status was significantly associated with time to isolated LRR (P=.04); patients with positive margins had a 5-year LRR of 6.2%, whereas patients with close margins and negative margins had 5-year LRRs of 1.5% and 1.9%, respectively. On univariate analysis, positive margins, positive nodes, lymphovascular invasion, grade 3 histology, and triple-negative subtype were associated with significantly higher rates of LRR. When these factors were included in a multivariate analysis, only positive margins and triple-negative subtype were associated with the risk of LRR. Conclusions: Patients with positive mastectomy margins had a significantly higher rate of LRR than those with a close or negative margin. However, the absolute risk of LRR in patients with a positive surgical margin in this series was low, and therefore the benefit of postmastectomy radiation in this population with otherwise favorable features

[Achievements and enlightenment of modern acupuncture therapy for stroke based on the neuroanatomy].

Science.gov (United States)

Chen, Li-Fang; Fang, Jian-Qiao; Chen, Lu-Ni; Wang, Chao

2014-04-01

Up to now, in the treatment of stroke patients by acupuncture therapy, three main representative achievements involving scalp acupuncture intervention, "Xing Nao Kai Qiao" (restoring consciousness and inducing resuscitation) acupuncture technique and nape acupuncture therapy have been got. Regarding their neurobiological mechanisms, the scalp acupuncture therapy is based on the functional localization of the cerebral cortex, "Xing Nao Kai Qiao" acupuncture therapy is closely related to nerve stem stimulation, and the nape acupuncture therapy is based on the nerve innervation of the regional neck-nape area in obtaining therapeutic effects. In fact, effects of these three acupuncture interventions are all closely associated with the modern neuroanatomy. In the treatment of post-stroke spastic paralysis, cognitive disorder and depression with acupuncture therapy, modern neuroanatomical knowledge should be one of the key theoretical basis and new therapeutic techniques should be explored and developed continuously.

Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids. Addendum

Science.gov (United States)

2009-08-01

Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids PRINCIPAL INVESTIGATOR: Cahit A. Evrensel...AND SUBTITLE 5a. CONTRACT NUMBER Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible... Magneto -rheological Fluid (MRF) iron nano-particles were synthesized using the reverse micelle technique and coated with poly(NIPAAm). The size

The mythology of anticoagulation therapy interruption for dental surgery.

Science.gov (United States)

Wahl, Michael J

2018-01-01

Continuous anticoagulation therapy is used to prevent heart attacks, strokes, and other embolic complications. When patients receiving anticoagulation therapy undergo dental surgery, a decision must be made about whether to continue anticoagulation therapy and risk bleeding complications or briefly interrupt anticoagulation therapy and increase the risk of developing embolic complications. Results from decades of studies of thousands of dental patients receiving anticoagulation therapy reveal that bleeding complications requiring more than local measures for hemostasis have been rare and never fatal. However, embolic complications (some of which were fatal and others possibly permanently debilitating) sometimes have occurred in patients whose anticoagulation therapy was interrupted for dental procedures. Although there is now virtually universal consensus among national medical and dental groups and other experts that anticoagulation therapy should not be interrupted for most dental surgery, there are still some arguments made supporting anticoagulation therapy interruption. An analysis of these arguments shows them to be based on a collection of myths and half-truths rather than on logical scientific conclusions. The time has come to stop anticoagulation therapy interruption for dental procedures. Copyright © 2018 American Dental Association. Published by Elsevier Inc. All rights reserved.

Multimodal therapy for locally advanced prostate cancer: the roles of radiotherapy, androgen deprivation therapy, and their combination

Energy Technology Data Exchange (ETDEWEB)

Lee, Sung Uk; Cho, Kwan Ho [The Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)

2017-09-15

Locally advanced prostate cancer (LAPC) is defined as histologically proven T3–4 prostatic adenocarcinoma. In this review, we define the individual roles of radiotherapy (RT), short-term (ST-) and long-term (LT-) androgen deprivation therapy (ADT), and their combination in multimodal therapy for LAPC. Despite limitations in comparing the clinical outcomes among published papers, in the present study, a trend of 10-year clinical outcomes was roughly estimated by calculating the average rates weighted by the cohort number. With RT alone, the following rates were estimated: 87% biochemical failure, 34% local failure (LF), 48% distant metastasis (DM), 38% overall survival (OS), and 27% disease-specific mortality (DSM). Those associated with ADT alone were 74% BCF, 54% OS, and 25% DSM, which appeared to be better than those of RT alone. The addition of ADT to RT produced a notable local and systemic effect, regardless of ST- or LT-ADT. The LF rate decreased from 34% with RT alone to 21% with ST-ADT and further to 15% with LT-ADT. The DM and DSM rates also showed a similar trend among RT alone, RT+ST-ADT, and RT+LT-ADT. The combination of RT+LT-ADT resulted in the best long-term clinical outcomes, indicating that both RT and ADT are important parts of multimodal therapy.

Multimodal therapy for locally advanced prostate cancer: the roles of radiotherapy, androgen deprivation therapy, and their combination

International Nuclear Information System (INIS)

Lee, Sung Uk; Cho, Kwan Ho

2017-01-01

Locally advanced prostate cancer (LAPC) is defined as histologically proven T3–4 prostatic adenocarcinoma. In this review, we define the individual roles of radiotherapy (RT), short-term (ST-) and long-term (LT-) androgen deprivation therapy (ADT), and their combination in multimodal therapy for LAPC. Despite limitations in comparing the clinical outcomes among published papers, in the present study, a trend of 10-year clinical outcomes was roughly estimated by calculating the average rates weighted by the cohort number. With RT alone, the following rates were estimated: 87% biochemical failure, 34% local failure (LF), 48% distant metastasis (DM), 38% overall survival (OS), and 27% disease-specific mortality (DSM). Those associated with ADT alone were 74% BCF, 54% OS, and 25% DSM, which appeared to be better than those of RT alone. The addition of ADT to RT produced a notable local and systemic effect, regardless of ST- or LT-ADT. The LF rate decreased from 34% with RT alone to 21% with ST-ADT and further to 15% with LT-ADT. The DM and DSM rates also showed a similar trend among RT alone, RT+ST-ADT, and RT+LT-ADT. The combination of RT+LT-ADT resulted in the best long-term clinical outcomes, indicating that both RT and ADT are important parts of multimodal therapy

Localized Scleroderma, Systemic Sclerosis and Cardiovascular Risk

DEFF Research Database (Denmark)

Hesselvig, Jeanette Halskou; Kofoed, Kristian; Wu, Jashin J

2018-01-01

Recent findings indicate that patients with systemic sclerosis have an increased risk of cardiovascular disease. To determine whether patients with systemic sclerosis or localized scleroderma are at increased risk of cardiovascular disease, a cohort study of the entire Danish population aged ≥ 18...... and ≤ 100 years was conducted, followed from 1997 to 2011 by individual-level linkage of nationwide registries. Multivariable adjusted Cox regression models were used to estimate the hazard ratios (HRs) for a composite cardiovascular disease endpoint. A total of 697 patients with localized scleroderma and 1......,962 patients with systemic sclerosis were identified and compared with 5,428,380 people in the reference population. In systemic sclerosis, the adjusted HR was 2.22 (95% confidence interval 1.99-2.48). No association was seen between patients with localized scleroderma and cardiovascular disease. In conclusion...

Menopause and postmenopausal hormone therapy and risk of hearing loss.

Science.gov (United States)

Curhan, Sharon G; Eliassen, A Heather; Eavey, Roland D; Wang, Molin; Lin, Brian M; Curhan, Gary C

2017-09-01

Menopause may be a risk factor for hearing loss, and postmenopausal hormone therapy (HT) has been proposed to slow hearing decline; however, there are no large prospective studies. We prospectively examined the independent relations between menopause and postmenopausal HT and risk of self-reported hearing loss. Prospective cohort study among 80,972 women in the Nurses' Health Study II, baseline age 27 to 44 years, followed from 1991 to 2013. Baseline and updated information was obtained from detailed validated biennial questionnaires. Cox proportional-hazards regression models were used to examine independent associations between menopausal status and postmenopausal HT and risk of hearing loss. After 1,410,928 person-years of follow-up, 18,558 cases of hearing loss were reported. There was no significant overall association between menopausal status, natural or surgical, and risk of hearing loss. Older age at natural menopause was associated with higher risk. The multivariable-adjusted relative risk of hearing loss among women who underwent natural menopause at age 50+ years compared with those aged less than 50 years was 1.10 (95% confidence interval [CI] 1.03, 1.17). Among postmenopausal women, oral HT (estrogen therapy or estrogen plus progestogen therapy) was associated with higher risk of hearing loss, and longer duration of use was associated with higher risk (P trend menopause and longer duration of postmenopausal HT are associated with higher risk of hearing loss.

3D conformal radiation therapy and hormonal therapy for localized prostate cancer: Is age a limiting factor?

International Nuclear Information System (INIS)

Faure, A.; Negrea, T.; Lechevallier, E.; Coulange, C.; Murraciole, X.; Jouvea, E.; Sambuca, R.; Cowen, D.

2011-01-01

No study on side effects had showed that conformal radiation therapy for prostate cancer is more harmful in patients older than 70 years to patients younger. The aim of this study was to evaluate acute and late toxicities of conformal radiotherapy, with high dose for localized prostate cancer in patients older than 70 years and compared to patients younger than 70 years. Between 1996 and 2009, 104 patients were treated with radiation therapy and hormonal therapy for localized cancer prostate. Median follow-up was 105 months (9 300). Acute (occurred at ≤ three months) and late side effects of 55 patients older than 70 years (median age: 75 [71 92]) were graded according to the CTCAE 3.0 criteria and compared to the younger population. Median dose to the prostate was 75.6 Gy (67 80) in both groups. There were no significant differences in acute and late side effects between age groups. For patients above 70 years, the incidence of grade II or higher acute and late side effects were respectively 27 and 22% for urologic symptoms and 13 and 16% for rectal symptoms. The frequency of grade III late symptoms was low and ranged between 0 and 6% for the evaluated symptoms, irrespective of age group. Older patients had a better biochemical recurrence-free survival than younger patients (86 versus 77% at four years, P ≡ ns). High dose 3D conformal radiotherapy for localized prostate cancer was well tolerated in patients older than 70 years. Age is not a limiting factor for conformal radiation therapy and hormonotherapy for older patients. (authors)

Prospective evaluation of early treatment outcome in patients with meningiomas treated with particle therapy based on target volume definition with MRI and {sup 68}Ga-DOTATOC-PET

Energy Technology Data Exchange (ETDEWEB)

Combs, Stephanie E.; Welzel, Thomas; Habermehl, Daniel; Rieken, Stefan; Dittmar, Jan-Oliver; Kessel, Kerstin; Debus, Juergen [Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany)], e-mail: Stephanie.Combs@med.uni-heidelberg.de; Jaekel, Oliver [Heidelberg Ion Therapy Center (HIT), Heidelberg (Germany); Haberkorn, Uwe [Univ. Hospital of Heidelberg, Dept. of Nuclear Medicine, Heidelberg (Germany)

2013-04-15

Purpose: To evaluate early treatment results and toxicity in patients with meningiomas treated with particle therapy. Material and methods: Seventy patients with meningiomas were treated with protons (n = 38) or carbon ion radiotherapy (n = 26). Median age was 49 years. Median age at treatment was 55 years, 24 were male (34%), and 46 were female (66%). Histology was benign meningioma in 26 patients (37%), atypical in 23 patients (33%) and anaplastic in four patients (6%). In 17 patients (24%) with skull base meningiomas diagnosis was based on the typical appearance of a meningioma. For benign meningiomas, total doses of 52.2-57.6 GyE were applied with protons. For high-grade lesions, the boost volume was 18 GyE carbon ions, with a median dose of 50 GyE applied as highly conformal radiation therapy. Nineteen patients were treated as re-irradiation. Treatment planning with MRI and 68-Ga-DOTATOC-PET was evaluated. Results: Very low rates of side effects developed, including headaches, nausea and dizziness. No severe treatment-related toxicity was observed. Local control for benign meningiomas was 100%. Five of 27 patients (19%) developed tumor recurrence during follow-up. Of these, four patients had been treated as re-irradiation for recurrent high-risk meningiomas. Actuarial local control after re-irradiation of high-risk meningiomas was therefore 67% at six and 12 months. In patients treated with primary radiotherapy, only one of 13 patients (8%) developed tumor recurrence 17 months after radiation therapy (photon and carbon ion boost). Conclusion: Continuous prospective follow-up and development of novel study concepts are required to fully exploit the long-term clinical data after particle therapy for meningiomas. To date, it may be concluded that when proton therapy is available, meningioma patients can be offered a treatment at least comparable to high-end photon therapy.

Locally advanced cervix carcinoma - innovation in combined modality therapy

International Nuclear Information System (INIS)

Swift, Patrick S.

1996-01-01

Locally advanced cervical carcinoma continues to be a challenge to the clinician due to local failure as well as systemic metastases. Standard intracavitary and external beam techniques result in local control rates of only 35-65%, with long term survival rates of 25-60% in patients with state IIIA-IVA disease, indicating the need to identify new treatment strategies. Optimization programs for remote-afterloading interstitial brachytherapy allow the delivery of higher local doses of radiation to volumes that more closely approximate tumor target volumes as identified on MR scans, leading to improved therapeutic ratios. Identification of subsets of patients more likely to fail standard therapy, either locally or systemically, may be possible through such techniques as in vivo measurements of hypoxia with Eppendorf oxygen electrodes, interstitial fluid pressure measurements, the Comet assay, and nitroimidazole binding methods. Traditional chemotherapies, administered in either a neoadjuvant role or concomitantly with radiation have been disappointing in prospective trials. A variety of new agents are being investigated to determine if they can increase the frequency or duration of complete response. The taxanes, with response rates of 17-23% by themselves, are being assessed as potential radiosensitizers. The camptotheicin CRT-11 (Irinotecan) has demonstrated activity in platinum resistant cervix cancer, with response rates of 24%. Bioradiotherapeutic approaches, using 13-cis-retinoic acid and interferon-2a, are undergoing phase II studies. Neoangiogenesis inhibitors and vaccines against HPV are also being examined. The aggressive pursuit of techniques that help identify those patients most likely to fail, that allow the delivery of higher radiation doses more safely to the target volume, and that incorporate the use of more effective systemic therapies is necessary to improve the outcome for this disease

Local and systemic antimicrobial therapy in periodontics.

Science.gov (United States)

Herrera, David; Matesanz, Paula; Bascones-Martínez, Antonio; Sanz, Mariano

2012-09-01

This review aimed to update the current evidence on the efficacy of the adjunctive use of local and systemic antimicrobials in the treatment of periodontitis and to assess whether it might improve the clinical limitations and shortcomings of standard nonsurgical treatment in the management of periodontitis. Relevant randomized clinical trials (RCT) with more than 3 months of follow-up, published from 2010 to 2012 for systemic antimicrobials and from 2008 to 2012 for local antimicrobials, were searched in Medline and critically analyzed. Scientific evidence evaluated in different systematic reviews and reviews presented at European and World Workshops were also included. Only adjunctive therapies were considered in the present review: articles comparing debridement alone or plus placebo, versus debridement plus systemic or local antimicrobials were included. Adjunctive systemic antimicrobials have been evaluated both in aggressive and chronic periodontitis: in aggressive periodontitis, amoxicillin and metronidazole have been extensively studied, reporting clinical and microbiological benefits; in chronic periodontitis, different products are under scrutiny, such as azithromycin. The clinical efficacy of local antimicrobials, although extensively demonstrated, is still surrounded by a constant debate on the cost-effectiveness evaluation and on its adequate indications. Despite the clinical efficacy of the adjunctive use of local and systemic antimicrobials, demonstrated in RCTs and in systematic reviews, there is a lack of evidence to support well-defined clinical protocols, including products and dosages. Copyright © 2012 Elsevier Inc. All rights reserved.

The effect of telephone-based cognitive-behavioural therapy on parenting stress: A randomised controlled trial.

Science.gov (United States)

Ngai, Fei Wan; Wong, Paul Wai-Ching; Chung, Ka Fai; Leung, Kwok Yin

2016-07-01

Objective Stress related to parenting has detrimental effects on the well-being of children, parents and the family system as a whole. There are limited studies about the efficacy of cognitive-behavioural therapy delivered by telephone in reducing parenting stress. The present study investigates the effect of telephone-based cognitive-behavioural therapy on parenting stress at six weeks and six months postpartum. This is a multi-site randomised controlled trial. A total of 397 Chinese mothers at risk of postnatal depression were randomly assigned to receive either telephone-based cognitive-behavioural therapy or routine postpartum care. Parental stress was assessed by the Parenting Stress Index Short Form at six weeks and six months postpartum. The findings revealed that mothers who had received telephone-based cognitive-behavioural therapy showed significantly lower levels of parenting stress than women only receiving routine postpartum care at six weeks (mean difference=9.42, 95% confidence interval 5.85-12.99, pparenting and reducing stress during the transition period. Integration of telephone-based cognitive-behavioural therapy into routine postpartum care might facilitate positive adaptation in particular for mothers at risk of postnatal depression. Copyright © 2016. Published by Elsevier Inc.

Moving away from local-based flood risk policy in Austria

Directory of Open Access Journals (Sweden)

Thomas Thaler

2016-01-01

Full Text Available Floodplain areas across the world have always played an attractive role for residential and non-residential developments. The Alpine regions have a strong pressure to develop new residential and non-residential buildings in hazard areas due to lack of other areas suitable for development. Consequently, the number of elements at risk and vulnerability to flood hazards increased. In order to reduce the vulnerability, the focus of mitigation flood hazards was for decades on structural engineering measures with the problem of spatial misfits between the threat and management strategy. Since the late 1990s/early 2000s, Austrian policy makers have been trying to overcome this spatial misfit with the implementation of an inter-local co-operation approach with the use of so-called ‘new spatial planning’ (Heley, 2013 in the planning process. Therefore, the paper examines what the actors and stakeholders are doing in practice and how the concept of fuzziness helps. Although a partnership approach may be seen as a promising solution, in practice there are many limitations and barriers in establishing these collaborations and making them effective (especially in the long term. Rhetoric may not be matched by reality and a ‘partnership’ agenda may bring more problems (i.e. high transactions costs, high risk of failure, uncertainty in the long term than it solves.

Benefits of statin therapy and compliance in high risk cardiovascular patients

Directory of Open Access Journals (Sweden)

Joel A Lardizabal

2010-09-01

Full Text Available Joel A Lardizabal1, Prakash C Deedwania21Division of Cardiology, Department of Medicine, University of California in San Francisco (Fresno-MEP, Fresno, CA, USA; 2University of California in San Francisco, Chief of Cardiology, Veterans Affairs Central California System, Fresno, CA, USAAbstract: Cardiovascular disease (CVD remains the top cause of global mortality. There is considerable evidence that supports the mortality and morbidity benefit of statin therapy in coronary heart disease (CHD and stroke, both in primary and secondary prevention settings. Data also exist pointing to the advantage of statin treatment in other high-risk CVD conditions, such as diabetes, CKD, CHF, and PVD. National and international clinical guidelines in the management of these CVD conditions all advocate for the utilization of statin therapy in appropriate patients. However, overall compliance to statin therapy remains suboptimal. Patient-, physician-, and economic-related factors all play a role. These factors need to be considered in devising approaches to enhance adherence to guideline-based therapies. To fully reap the benefits of statin therapy, interventions which improve long-term treatment compliance in real-world settings should be encouraged.Keywords: cardiovascular disease, statin therapy, coronary heart disease, long-term treatment compliance

Local recurrence risk after previous salvage mastectomy.

Science.gov (United States)

Tanabe, M; Iwase, T; Okumura, Y; Yoshida, A; Masuda, N; Nakatsukasa, K; Shien, T; Tanaka, S; Komoike, Y; Taguchi, T; Arima, N; Nishimura, R; Inaji, H; Ishitobi, M

2016-07-01

Breast-conserving surgery is a standard treatment for early breast cancer. For ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery, salvage mastectomy is the current standard surgical procedure. However, it is not rare for patients with IBTR who have received salvage mastectomy to develop local recurrence. In this study, we examined the risk factors of local recurrence after salvage mastectomy for IBTR. A total of 118 consecutive patients who had histologically confirmed IBTR without distant metastases and underwent salvage mastectomy without irradiation for IBTR between 1989 and 2008 were included from eight institutions in Japan. The risk factors of local recurrence were assessed. The median follow-up period from salvage mastectomy for IBTR was 4.6 years. Patients with pN2 or higher on diagnosis of the primary tumor showed significantly poorer local recurrence-free survival than those with pN0 or pN1 at primary tumor (p mastectomy for IBTR. Further research and validation studies are needed. (UMIN-CTR number UMIN000008136). Copyright © 2016 Elsevier Ltd. All rights reserved.

Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

Science.gov (United States)

Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W

2016-01-01

Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

Directory of Open Access Journals (Sweden)

Ryan C Curtis

Full Text Available Clinical studies using definitive-intent stereotactic radiation therapy (SRT for the local treatment of canine osteosarcoma (OSA have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy. Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA and parathyroid hormone (PTH are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total. Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis 8 weeks after radiation in the combined (ZA/PTH treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

Risk of secondary malignancies after radiation therapy for breast cancer: Comprehensive results.

Science.gov (United States)

Burt, Lindsay M; Ying, Jian; Poppe, Matthew M; Suneja, Gita; Gaffney, David K

2017-10-01

To assess risks of secondary malignancies in breast cancer patients who received radiation therapy compared to patients who did not. The SEER database was used to identify females with a primary diagnosis of breast cancer as their first malignancy, during 1973-2008. We excluded patients with metastatic disease, age breast cancer recurrence, or who developed a secondary malignancy within 1 year of diagnosis. Standardized incidence ratios and absolute excess risk were calculated using SEER*Stat, version 8.2.1 and SAS, version 9.4. There were 374,993 patients meeting the inclusion criteria, with 154,697 who received radiation therapy. With a median follow-up of 8.9 years, 13% of patients (49,867) developed a secondary malignancy. The rate of secondary malignancies was significantly greater than the endemic rate in breast cancer patients treated without radiation therapy, (O/E 1.2, 95% CI 1.19-1.22) and with radiation therapy (O/E 1.33, 95% CI 1.31-1.35). Approximately 3.4% of secondary malignancies were attributable to radiation therapy. The increased risk of secondary malignancies in breast cancer patients treated with radiation therapy compared to those without was significant regardless of age at breast cancer diagnosis (p breast cancer patients both with and without radiation therapy compared to the general population. There was an increased risk in specific sites for patients treated with radiation therapy. This risk was most evident in young patients and who had longer latency periods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Radiation risk education program - local

International Nuclear Information System (INIS)

Bushong, S.C.; Archer, B.R.

1980-01-01

This article points out the lack of knowledge by the general public and medical profession concerning the true risks of radiation exposure. The author describes an educational program which can be implemented at the local level to overcome this deficiency. The public must understand the enormous extent of benefit derived from radiation applications in our society

Views from the Frontline: A critical assessment of local risk governance in South Africa

Directory of Open Access Journals (Sweden)

Doret Botha

2013-02-01

Full Text Available In 2005 the United Nations International Strategy for Disaster Reduction introduced the ‘Hyogo Framework for Action’ (HFA aimed at mainstreaming disaster risk reduction. Subsequently, the ‘Global Network for Disaster Reduction’ (GNDR was formed to support the implementation of the HFA. The GNDR initiated a country-based, international research project called ‘Views from the Frontline’ (VFL in order to measure progress at local level in terms of compliance with the HFA. The VFL 2011 project focused on local risk governance, which is critical for effective implementation of policy and provision of resources at grassroots level. This article provides insight into the findings for South Africa. The project made use of quantitative and qualitative data. Quantitative data was gathered by means of a survey and/or questionnaire consisting of 20 questions on ‘indicators’ which assessed progress toward the goals of the HFA. The surveys also provided for qualitative commentary. The target population for this research consisted of local government officials and community representatives. Based on the quantitative scores for all the different indicators, the research showed that South Africa could still improve significantly in terms of compliance with the HFA. More attention must be given to operationalise the HFA at local level, a culture of safety must be fostered, local actors and communities must be involved directly and consulted, indigenous knowledge must be recognised, and significant capacity development for disaster risk reduction is necessary.

Applying Four Different Risk Models in Local Ore Selection

International Nuclear Information System (INIS)

Richmond, Andrew

2002-01-01

Given the uncertainty in grade at a mine location, a financially risk-averse decision-maker may prefer to incorporate this uncertainty into the ore selection process. A FORTRAN program risksel is presented to calculate local risk-adjusted optimal ore selections using a negative exponential utility function and three dominance models: mean-variance, mean-downside risk, and stochastic dominance. All four methods are demonstrated in a grade control environment. In the case study, optimal selections range with the magnitude of financial risk that a decision-maker is prepared to accept. Except for the stochastic dominance method, the risk models reassign material from higher cost to lower cost processing options as the aversion to financial risk increases. The stochastic dominance model usually was unable to determine the optimal local selection

Three-Dimensional Conformal Radiation Therapy and Intensity-Modulated Radiation Therapy Combined With Transcatheter Arterial Chemoembolization for Locally Advanced Hepatocellular Carcinoma: An Irradiation Dose Escalation Study

International Nuclear Information System (INIS)

Ren Zhigang; Zhao Jiandong; Gu Ke; Chen Zhen; Lin Junhua; Xu Zhiyong; Hu Weigang; Zhou Zhenhua; Liu Luming; Jiang Guoliang

2011-01-01

Purpose: To determine the maximum tolerated dose (MTD) of three-dimensional conformal radiation therapy (3DCRT)/intensity-modulated radiation therapy (IMRT) combined with transcatheter arterial chemoembolization for locally advanced hepatocellular carcinoma. Methods and Materials: Patients were assigned to two subgroups based on tumor diameter: Group 1 had tumors <10 cm; Group II had tumors ≥10 cm. Escalation was achieved by increments of 4.0 Gy for each cohort in both groups. Dose-limiting toxicity (DLT) was defined as a grade of ≥3 acute liver or gastrointestinal toxicity or any grade 5 acute toxicity in other organs at risk or radiation-induced liver disease. The dose escalation would be terminated when ≥2 of 8 patients in a cohort experienced DLT. Results: From April 2005 to May 2008, 40 patients were enrolled. In Group I, 11 patients had grade ≤2 acute treatment-related toxicities, and no patient experienced DLT; and in Group II, 10 patients had grade ≤2 acute toxicity, and 1 patient in the group receiving 52 Gy developed radiation-induced liver disease. MTD was 62 Gy for Group I and 52 Gy for Group II. In-field progression-free and local progression-free rates were 100% and 69% at 1 year, and 93% and 44% at 2 years, respectively. Distant metastasis rates were 6% at 1 year and 15% at 2 years. Overall survival rates for 1-year and 2-years were 72% and 62%, respectively. Conclusions: The irradiation dose was safely escalated in hepatocellular carcinoma patients by using 3DCRT/IMRT with an active breathing coordinator. MTD was 62 Gy and 52 Gy for patients with tumor diameters of <10 cm and ≥10 cm, respectively.

Risk Factors for Incident Diabetes in a Cohort Taking First-Line Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy.

Science.gov (United States)

Karamchand, Sumanth; Leisegang, Rory; Schomaker, Michael; Maartens, Gary; Walters, Lourens; Hislop, Michael; Dave, Joel A; Levitt, Naomi S; Cohen, Karen

2016-03-01

Efavirenz is the preferred nonnucleoside reverse transcriptase inhibitor (NNRTI) in first-line antiretroviral therapy (ART) regimens in low- and middle-income countries, where the prevalence of diabetes is increasing. Randomized control trials have shown mild increases in plasma glucose in participants in the efavirenz arms, but no association has been reported with overt diabetes. We explored the association between efavirenz exposure and incident diabetes in a large Southern African cohort commencing NNRTI-based first-line ART. Our cohort included HIV-infected adults starting NNRTI-based ART in a private sector HIV disease management program from January 2002 to December 2011. Incident diabetes was identified by the initiation of diabetes treatment. Patients with prevalent diabetes were excluded. We included 56,298 patients with 113,297 patient-years of follow-up (PYFU) on first-line ART. The crude incidence of diabetes was 13.24 per 1000 PYFU. Treatment with efavirenz rather than nevirapine was associated with increased risk of developing diabetes (hazard ratio 1.27 (95% confidence interval (CI): 1.10-1.46)) in a multivariate analysis adjusting for age, sex, body mass index, baseline CD4 count, viral load, NRTI backbone, and exposure to other diabetogenic medicines. Zidovudine and stavudine exposure were also associated with an increased risk of developing diabetes. We found that treatment with efavirenz, as well as stavudine and zidovudine, increased the risk of incident diabetes. Interventions to detect and prevent diabetes should be implemented in ART programs, and use of antiretrovirals with lower risk of metabolic complications should be encouraged.

Morbidity in patients with clinically localized prostate cancer managed with non-curative intent. A population-based case-control study

DEFF Research Database (Denmark)

Brasso, Klaus; Friis, S; Juel, K

1999-01-01

. When prostate cancer-related admissions were excluded, the relative risk of admission was reduced to 1.35 (1.3-1.4) and 0.86 (0.83-0.89), respectively. The estimated costs associated with deferred therapy in patients with clinically localized prostate cancer exceeded the estimated cost in age...

Evaluation of primary androgen deprivation therapy in prostate cancer patients using the J-CAPRA risk score

Science.gov (United States)

Akaza, Hideyuki; Hinotsu, Shiro; Usami, Michiyuki; Ogawa, Osamu; Kitamura, Tadaichi; Suzuki, Kazuhiro; Tsukamoto, Taiji; Naito, Seiji; Namiki, Mikio; Hirao, Yoshihiko; Murai, Masaru

2013-01-01

Purpose: To determine the influence of maximal androgen blockade (MAB) and non-MAB hormonal therapy with an luteinizing hormone releasing hormone (LHRH) analog on overall survival of prostate cancer patients in the Japan Study Group of Prostate Cancer (J-CaP) registry according to risk, as assessed using the novel J-CAPRA risk instrument. To undertake a multivariate analysis combining J-CAPRA risk score, type of hormonal therapy and comorbidities, in order to assess their impact on overall survival. Methods: The J-CaP database includes men in Japan diagnosed with any stage of prostate cancer between 2001 and 2003 and treated with primary androgen deprivation therapy (PADT), as monotherapy or in combination. A total of 26,272 men were enrolled and of these 19,265 were treated with PADT. This analysis was undertaken using the latest data set (30 April, 2010) including a total of 15,727 patients who received PADT and had follow-up data for periods ranging from 0 to 9.2 years. Results: MAB for prostate cancer patients with intermediate- or high-risk disease has a significant benefit in terms of overall survival compared with LHRH analog monotherapy or surgical castration alone. Better results may be achieved in older (≥75 years) patients. Patient comorbidities are an important factor in determining overall survival, notably in older patients, and should be considered when selecting therapy. Conclusions: Based on large-scale registry data, this report is the first to analyze the outcomes of MAB therapy in patients with prostate cancer at a wide range of disease stages. MAB therapy may provide significant survival benefits in intermediate- and high-risk patients. PMID:24223407

Cost-effectiveness of carbon ion radiation therapy for locally recurrent rectal cancer

International Nuclear Information System (INIS)

Mobaraki, A.; Ohno, Tatsuya; Sakurai, Hideyuki; Nakano, Takashi; Yamada Shigeru

2010-01-01

The aim of this study was to evaluate the cost-effectiveness of carbon ion radiotherapy compared with conventional multimodality therapy in the treatment of patients with locally recurrent rectal cancer. Direct costs for diagnosis, recurrent treatment, follow-up, visits, supportive therapy, complications, and admission were computed for each individual using a sample of 25 patients presenting with local recurrent rectal cancer at the National Institute of Radiological Science (NIRS) and Gunma University Hospital (GUH). Patients received only radical surgery for primary rectal adenocarcinoma and had isolated unresectable pelvic recurrence. Fourteen and 11 patients receiving treatment for the local recurrence between 2003 and 2005 were followed retrospectively at NIRS and GUH, respectively. Treatment was carried out with carbon ion radiotherapy (CIRT) alone at NIRS, while multimodality therapy including three-dimensional conformal radiotherapy, chemotherapy, and hyperthermia was performed at GUH. The 2-year overall survival rate was 85% and 55% for CIRT and multimodality treatment, respectively. The mean cost was 4803946 yen for the CIRT group and 4611100 yen for the multimodality treatment group. The incremental cost-effectiveness ratio for CIRT was 6428 yen per 1% increase in survival. The median duration of total hospitalization was 37 days for CIRT and 66 days for the multimodality treatment group. In conclusion, by calculating all direct costs, CIRT was found to be a potential cost effective treatment modality as compared to multimodality treatment for locally recurrent rectal cancer. (author)

Fracture risk and zoledronic acid therapy in men with osteoporosis

DEFF Research Database (Denmark)

Boonen, Steven; Reginster, Jean-Yves; Kaufman, Jean-Marc

2012-01-01

Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis.......Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis....

Mindfulness-based cognitive therapy for depression: trends and developments.

Science.gov (United States)

MacKenzie, Meagan B; Kocovski, Nancy L

2016-01-01

Mindfulness-based cognitive therapy (MBCT) was developed as a psychological intervention for individuals at risk of depressive relapse. Possible mechanisms of change for this intervention are in line with its theoretical underpinnings, and include increases in mindfulness and/or decreases in negative repetitive thoughts. This review provides an overview of current trends in MBCT research, including efficacy and questions regarding the specific effects of MBCT in light of recent comparisons with structurally equivalent control conditions, mechanisms of change, and moderators of treatment outcome. In addition, future directions are discussed, such as challenges with training an adequate number of therapists and disseminating this therapy.

Intraoperative radiation therapy for locally advanced gynecological malignancies

International Nuclear Information System (INIS)

Haddock, M.G.; Petersen, I.A.; Webb, M.J.; Wilson, T.O.; Podratz, K.C.; Gunderson, L.L.

1996-01-01

Purpose: Evaluate disease control and survival in patients with locally advanced gynecological malignancies who received intraoperative radiation therapy with electrons (IOERT) as a component of treatment. Methods and Materials: Between March 1983 and June 1995, 63 patients (pts) with locally advanced primary (9 pts) or recurrent (54 pts) gynecological malignancies received IOERT as a component of attempted curative therapy. The site of origin was uterine cervix in 40 pts, uterine corpus in 16 pts, vagina in 5 pts, and ovary in 2 pts. Thirty-eight patients with recurrent disease had been previously irradiated (median prior RT dose 5040 cGy, range 900-8400). External beam radiotherapy (EBRT) was given to 43 of 63 pts either before or after IOERT (900-6570 cGy, median 4960 cGy). Chemotherapy was given to 21 pts prior to IOERT and following IOERT in 2 pts. IOERT doses ranged from 800 cGy to 2500 cGy with a median of 1750 cGy. The median IOERT dose was 2000 cGy in 20 patients with gross residual disease and 1500 cGy in 43 patients with microscopic residual disease. Endpoints included central control within the IOERT cone, local control, distant failure, disease free survival and overall survival. Variables evaluated for impact on disease outcome included tumor grade, primary site, prior RT, IOERT dose, EBRT dose, residual disease at time of IOERT, and use of chemotherapy. Results: Survival and disease control data are presented in the table below. There was no impact of any disease or treatment related variable on local or central failure. Pts with microscopic residual disease at the time of IOERT had significantly fewer distant metastases than pts with gross residual (5 yr 31% vs. 77%, p = 0.001) and improved survival (5 yr 37% vs. 10%, p = 0.02). Patients with recurrent disease after previous RT had survival and disease control rates which were similar to those seen in pts without priot RT. Toxicity ≥ grade 3 due to IOERT was observed in 11 pts (17%). Conclusion: A

Cardiovascular event-free survival after adjuvant radiation therapy in breast cancer patients stratified by cardiovascular risk

International Nuclear Information System (INIS)

Onwudiwe, Nneka C; Kwok, Young; Onukwugha, Eberechukwu; Sorkin, John D; Zuckerman, Ilene H; Shaya, Fadia T; Daniel Mullins, C

2014-01-01

The objective of this study was to estimate the risk of a cardiovascular event or death associated with modern radiation in a population of elderly female breast cancer patients with varying baseline cardiovascular risk. The data used for this analysis are from the linked Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. The retrospective cohort study included women aged 66 years and older with stage 0–III breast cancer diagnosed between 2000 and 2005. Women were grouped as low, intermediate, or high cardiovascular risk based on the presence of certain clinical diagnoses. The risk for the combined outcome of a hospitalization for a cardiovascular event or death within 6 months and 24 months of diagnosis was estimated using a multivariable Cox model. The median follow-up time was 24 months. Among the 91,612 women with American Joint Committee on Cancer (AJCC) stage 0–III breast cancer: 39,555 (43.2%) were treated with radiation therapy and 52,057 (56.8%) were not. The receipt of radiation therapy in the first 6 months was associated with a statistically significant increased risk for the combined outcome in women categorized as high risk (HR = 1.510; 95% CI, 1.396–1.634) or intermediate risk (HR = 1.415; 95% CI, 1.188–1.686) but not low risk (HR = 1.027; 95% CI, 0.798–1.321). Women with a prior medical history of cardiovascular disease treated with radiation therapy are at increased risk for an event and should be monitored for at least 6 months following treatment with radiation therapy

Therapy strategy for intracranial germ-cell tumours and initial results of the GPO therapy study MAKEI 86

International Nuclear Information System (INIS)

Goebel, U.; Calaminus, G.; Haasenritter, N.

1988-01-01

Pineal tumours are increasingly identified histologically since the introduction of the surgical microscope and microsurgical techniques. A major biological characteristic of germ-cell tumours is the fact that they produce tumour markers. Meaningful therapy planning is determined by the biological behaviour of the individual tumour entity which is strongly influenced by its intracranial localization. Important risk factors need to be identified and weighted according to previous treatment in order to arrive at an adequate therapy with improved curative prospects. Three risk areas can be defined for tumour extension. Therapy planning is also determined by the metastatic spread behaviour of germ-cell tumours. Within the two therapy studies for nontesticular germ-cell tumours MAKEI 83 and 86, a total of 180 germ-cell tumours, 24 of which were localized intercranially, were reported from 46 different clinics. All patients have a survival probability according to Kaplan and Meier of 67 ± 10% at an observation duration of 48 months. (orig./MG) [de

Validating a Local Failure Risk Stratification for Use in Prospective Studies of Adjuvant Radiation Therapy for Bladder Cancer

International Nuclear Information System (INIS)

Baumann, Brian C.; He, Jiwei; Hwang, Wei-Ting; Tucker, Kai N.; Bekelman, Justin E.; Herr, Harry W.; Lerner, Seth P.; Guzzo, Thomas J.; Malkowicz, S. Bruce; Christodouleas, John P.

2016-01-01

Purpose: To inform prospective trials of adjuvant radiation therapy (adj-RT) for bladder cancer after radical cystectomy, a locoregional failure (LF) risk stratification was proposed. This stratification was developed and validated using surgical databases that may not reflect the outcomes expected in prospective trials. Our purpose was to assess sources of bias that may affect the stratification model's validity or alter the LF risk estimates for each subgroup: time bias due to evolving surgical techniques; trial accrual bias due to inclusion of patients who would be ineligible for adj-RT trials because of early disease progression, death, or loss to follow-up shortly after cystectomy; bias due to different statistical methods to estimate LF; and subgrouping bias due to different definitions of the LF subgroups. Methods and Materials: The LF risk stratification was developed using a single-institution cohort (n=442, 1990-2008) and the multi-institutional SWOG 8710 cohort (n=264, 1987-1998) treated with radical cystectomy with or without chemotherapy. We evaluated the sensitivity of the stratification to sources of bias using Fine-Gray regression and Kaplan-Meier analyses. Results: Year of radical cystectomy was not associated with LF risk on univariate or multivariate analysis after controlling for risk group. By use of more stringent inclusion criteria, 26 SWOG patients (10%) and 60 patients from the single-institution cohort (14%) were excluded. Analysis of the remaining patients confirmed 3 subgroups with significantly different LF risks with 3-year rates of 7%, 17%, and 36%, respectively (P<.01), nearly identical to the rates without correcting for trial accrual bias. Kaplan-Meier techniques estimated higher subgroup LF rates than competing risk analysis. The subgroup definitions used in the NRG-GU001 adj-RT trial were validated. Conclusions: These sources of bias did not invalidate the LF risk stratification or substantially change the model's LF estimates.

Postoperative chemoradiotherapy in high risk locally advanced gastric cancer

Energy Technology Data Exchange (ETDEWEB)

Song, Sang Hyuk; Chie, Eui Kyu; Kim, Kyu Bo; Lee, Hyuk Joon; Yang, Han Kwang; Han, Sae Won; Oh, Do Youn; Im, Seok Ah; Bang, Yung Jue; Ha, Sung W. [Seoul National University College of Medicine, Seoul(Korea, Republic of)

2012-12-15

To evaluate treatment outcome of patients with high risk locally advanced gastric cancer after postoperative chemoradiotherapy. Between May 2003 and May 2012, thirteen patients who underwent postoperative chemoradiotherapy for gastric cancer with resection margin involvement or adjacent structure invasion were retrospectively analyzed. Concurrent chemotherapy was administered in 10 patients. Median dose of radiation was 50.4 Gy (range, 45 to 55.8 Gy). The median follow-up duration for surviving patients was 48 months (range, 5 to 108 months). The 5-year overall survival rate was 42% and the 5-year disease-free survival rate was 28%. Major pattern of failure was peritoneal seeding with 46%. Loco-regional recurrence was reported in only one patient. Grade 2 or higher gastrointestinal toxicity occurred in 54% of the patients. However, there was only one patient with higher than grade 3 toxicity. Despite reported suggested role of adjuvant radiotherapy with combination chemotherapy in gastric cancer, only very small portion of the patients underwent the treatment. Results from this study show that postoperative chemoradiotherapy provided excellent locoregional control with acceptable and manageable treatment related toxicity in patients with high risk locally advanced gastric cancer. Thus, postoperative chemoradiotherapy may improve treatment result in terms of locoregional control in these high risk patients. However, as these findings are based on small series, validation with larger cohort is suggested.

77 FR 24959 - Scientific Information Request on Local Therapies for Unresectable Primary Hepatocellular Carcinoma

Science.gov (United States)

2012-04-26

...The Agency for Healthcare Research and Quality (AHRQ) is seeking scientific information submissions from manufacturers of local, minimally invasive, medical devices for unresectable primary hepatocellular carcinoma (e.g., ablation, radiotherapy, or embolization devices). Scientific information is being solicited to inform our Comparative Effectiveness Review of Local Therapies for Unresectable Primary Hepatocellular Carcinoma, which is currently being conducted by the Evidence-based Practice Centers for the AHRQ Effective Health Care Program. Access to published and unpublished pertinent scientific information on this device will improve the quality of this comparative effectiveness review. AHRQ is requesting this scientific information and conducting this comparative effectiveness review pursuant to Section 1013 of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, Public Law 108-173.

Therapy of Ewing's sarcoma

International Nuclear Information System (INIS)

Dunst, J.; Sauer, R.

1993-01-01

Therapy of Ewing's sarcoma requires a qualified clinical, radiological, and pathohistological diagnosis and, in particular, an optimal therapy by an experienced team of oncological specialists. Important prognostic factors are the presence of hematogenous metastases at diagnosis, the initial tumor volume, the response to chemotherapy, and adequate local therapy. Presently, cure rates of more than 60% can be achieved for localized Ewing's sarcoma by combination of local therapy and chemotherapy. The four-drug combination VACA (vincristin, actinomycin D, cyclophosphamide, adriamycin) can be considered as cytostatic gold standard. More aggressive regimens (VAIA, EVAIA, autologous bone marrow transplant) may be beneficial in subgroups and are under investigation. Concerning local therapy adequate radiotherapy plays a major role and achieves the same survival rates as radical surgery, comparable patient selection provided. Several factors have impact on radiotherapeutic results, especially total dose (45 Gy large volume, 55 Gy to the primary tumor), target volume (safety margin at least 2 cm according to the pretreatment volume, at least 5 cm in proximal and distal extension of long bones), timing of radiotherapy (as early as possible) and quality of treatment. Radiotherapy as sole local treatment is indicated in inoperable lesions (spine, sacrum, skull) and in small, good-responding tumors. High-risk patients should receive combined radiotherapeutic-surgical treatment, preferably as pre-operative irradiation. The value of hyperfractionation is not yet proven despite theoretical advantages. (orig.) [de

Proton beam therapy in the management of skull base chordomas: systematic review of indications, outcomes, and implications for neurosurgeons.

Science.gov (United States)

Matloob, Samir A; Nasir, Haleema A; Choi, David

2016-08-01

Chordomas are rare tumours affecting the skull base. There is currently no clear consensus on the post-surgical radiation treatments that should be used after maximal tumour resection. However, high-dose proton beam therapy is an accepted option for post-operative radiotherapy to maximise local control, and in the UK, National Health Service approval for funding abroad is granted for specific patient criteria. To review the indications and efficacy of proton beam therapy in the management of skull base chordomas. The primary outcome measure for review was the efficacy of proton beam therapy in the prevention of local occurrence. A systematic review of English and non-English articles using MEDLINE (1946-present) and EMBASE (1974-present) databases was performed. Additional studies were reviewed when referenced in other studies and not available on these databases. Search terms included chordoma or chordomas. The PRISMA guidelines were followed for reporting our findings as a systematic review. A total of 76 articles met the inclusion and exclusion criteria for this review. Limitations included the lack of documentation of the extent of primary surgery, tumour size, and lack of standardised outcome measures. Level IIb/III evidence suggests proton beam therapy given post operatively for skull base chordomas results in better survival with less damage to surrounding tissue. Proton beam therapy is a grade B/C recommended treatment modality for post-operative radiation therapy to skull base chordomas. In comparison to other treatment modalities long-term local control and survival is probably improved with proton beam therapy. Further, studies are required to directly compare proton beam therapy to other treatment modalities in selected patients.

Controversial issue: is it safe to employ mesenchymal stem cells in cell-based therapies?

DEFF Research Database (Denmark)

Lepperdinger, Günter; Brunauer, Regina; Jamnig, Angelika

2008-01-01

The prospective clinical use of multipotent mesenchymal stromal stem cells (MSC) holds enormous promise for the treatment of a large number of degenerative and age-related diseases. However, the challenges and risks for cell-based therapies are multifaceted. The risks for patients receiving stem ...

[A Case of Locally Advanced Thoracic Esophageal Cancer with Larynx Preservation and Curative Resection via Combined Modality Therapy].

Science.gov (United States)

Iwama, Mitsuru; Kimura, Yutaka; Shiraishi, Osamu; Kato, Hiroaki; Hiraki, Yoko; Tanaka, Yumiko; Yasuda, Atsushi; Shinkai, Masayuki; Imano, Motohiro; Imamoto, Haruhiko; Yasuda, Takushi

2017-11-01

Prognosis of locally advanced esophageal cancer is poor. The greatest prognostic factor of locally advanced esophageal cancer is a local control. We experienced a case of T4 locally advanced thoracic esophageal cancer who was successfully resected without any combined resection after multimodality therapy. A male in 75-year-old. was diagnosed with type 3 locally advanced upper thoracic esophageal cancer whose metastatic right recurrent laryngeal lymph node invaded into the trachea. Definitive chemoradiation therapy(CRT)was performed, leading to a significant shrinkage of the main tumor, but T4 lesion remained. Next, adding DCF therapy(docetaxel, CDDP and 5-FU), a relief of T4 was finally obtained. Then, salvage surgery with subtotalesophagectomy and retrosternalesophagealreconstruction with gastric tube was performed, resulting in R0 resection without any combined resection. The postoperative course was uneventful, and the patient has been alive without recurrence for 1 year after surgery. In locally advanced cancer, focusing on T4 downstaging, it is significantly important in terms of safety, curativity and organ preservation to perform surgery after a sure sign of T4 relief by multimodality therapy.

STOMATOLOGIC ASPECTS IN THERAPY OF LOCALLY DISTRIBUTED CANCER OF ORAL CAVITY MUCUS

Directory of Open Access Journals (Sweden)

G. G. Matyakin

2013-01-01

Full Text Available Aim of the investigation: to improve prophylaxis of dental complications during the therapy in the patients with locally distributed cancer of oral cavity mucus.Materials. Results of sanation of oral cavity in 305 patients with cancer of oral and pharyngeal area are analyzed.Results. The best results are noted in the patients given surgical sanation before chemo-radial therapy. The most number of complications is observed when teeth were extracted after chemical therapy in the period of radial therapy at summary focal dose above 20 Gy as well as in the late periods after radial therapy.Conclusion. A complex of preventive measures with using haemostatic sponge with canamycin in such patients decreases the number of complications and the terms of healing of alveoli of extracted teeth.

Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program

DEFF Research Database (Denmark)

See, William A; Wirth, Manfred P; McLeod, David G

2002-01-01

We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer.......We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer....

A Randomized Trial (Irish Clinical Oncology Research Group 97-01) Comparing Short Versus Protracted Neoadjuvant Hormonal Therapy Before Radiotherapy for Localized Prostate Cancer.

LENUS (Irish Health Repository)

Armstrong, John G

2010-08-24

PURPOSE: To examine the long-term outcomes of a randomized trial comparing short (4 months; Arm 1) and long (8 months; Arm 2) neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer. METHODS AND MATERIALS: Between 1997 and 2001, 276 patients were enrolled and the data from 261 were analyzed. The stratification risk factors were prostate-specific antigen level >20 ng\\/mL, Gleason score >\\/=7, and Stage T3 or more. The intermediate-risk stratum had one factor and the high-risk stratum had two or more. Staging was done from the bone scan and computed tomography findings. The primary endpoint was biochemical failure-free survival. RESULTS: The median follow-up was 102 months. The overall survival, biochemical failure-free survival. and prostate cancer-specific survival did not differ significantly between the two treatment arms, overall or at 5 years. The cumulative probability of overall survival at 5 years was 90% (range, 87-92%) in Arm 1 and 83% (range, 80-86%) in Arm 2. The biochemical failure-free survival rate at 5 years was 66% (range, 62-71%) in Arm 1 and 63% (range, 58-67%) in Arm 2. CONCLUSION: No statistically significant difference was found in biochemical failure-free survival between 4 months and 8 months of neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer.

Hepatitis B virus reactivation during immunosuppressive therapy: Appropriate risk stratification.

Science.gov (United States)

Seto, Wai-Kay

2015-04-28

Our understanding of hepatitis B virus (HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen (HBsAg)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosis factor (anti-TNF) and hematopoietic stem cell transplantation (HSCT). HBV reactivation could also occur in HBsAg-negative, antibody to hepatitis B core antigen (anti-HBc) positive individuals during therapies containing rituximab, anti-TNF or HSCT.For HBsAg-positive patients, prophylactic antiviral therapy is proven to the effective in preventing HBV reactivation. Recent evidence also demonstrated entecavir to be more effective than lamivudine in this aspect. For HBsAg-negative, anti-HBc positive individuals, the risk of reactivations differs with the type of immunosuppression. For rituximab, a prospective study demonstrated the 2-year cumulative risk of reactivation to be 41.5%, but prospective data is still lacking for other immunosupressive regimes. The optimal management in preventing HBV reactivation would involve appropriate risk stratification for different immunosuppressive regimes in both HBsAg-positive and HBsAg-negative, anti-HBc positive individuals.

Creation of RTOG compliant patient CT-atlases for automated atlas based contouring of local regional breast and high-risk prostate cancers.

Science.gov (United States)

Velker, Vikram M; Rodrigues, George B; Dinniwell, Robert; Hwee, Jeremiah; Louie, Alexander V

2013-07-25

Increasing use of IMRT to treat breast and prostate cancers at high risk of regional nodal spread relies on accurate contouring of targets and organs at risk, which is subject to significant inter- and intra-observer variability. This study sought to evaluate the performance of an atlas based deformable registration algorithm to create multi-patient CT based atlases for automated contouring. Breast and prostate multi-patient CT atlases (n = 50 and 14 respectively) were constructed to be consistent with RTOG consensus contouring guidelines. A commercially available software algorithm was evaluated by comparison of atlas-predicted contours against manual contours using Dice Similarity coefficients. High levels of agreement were demonstrated for prediction of OAR contours of lungs, heart, femurs, and minor editing required for the CTV breast/chest wall. CTVs generated for axillary nodes, supraclavicular nodes, prostate, and pelvic nodes demonstrated modest agreement. Small and highly variable structures, such as internal mammary nodes, lumpectomy cavity, rectum, penile bulb, and seminal vesicles had poor agreement. A method to construct and validate performance of CT-based multi-patient atlases for automated atlas based auto-contouring has been demonstrated, and can be adopted for clinical use in planning of local regional breast and high-risk prostate radiotherapy.

Creation of RTOG compliant patient CT-atlases for automated atlas based contouring of local regional breast and high-risk prostate cancers

International Nuclear Information System (INIS)

Velker, Vikram M; Rodrigues, George B; Dinniwell, Robert; Hwee, Jeremiah; Louie, Alexander V

2013-01-01

Increasing use of IMRT to treat breast and prostate cancers at high risk of regional nodal spread relies on accurate contouring of targets and organs at risk, which is subject to significant inter- and intra-observer variability. This study sought to evaluate the performance of an atlas based deformable registration algorithm to create multi-patient CT based atlases for automated contouring. Breast and prostate multi-patient CT atlases (n = 50 and 14 respectively) were constructed to be consistent with RTOG consensus contouring guidelines. A commercially available software algorithm was evaluated by comparison of atlas-predicted contours against manual contours using Dice Similarity coefficients. High levels of agreement were demonstrated for prediction of OAR contours of lungs, heart, femurs, and minor editing required for the CTV breast/chest wall. CTVs generated for axillary nodes, supraclavicular nodes, prostate, and pelvic nodes demonstrated modest agreement. Small and highly variable structures, such as internal mammary nodes, lumpectomy cavity, rectum, penile bulb, and seminal vesicles had poor agreement. A method to construct and validate performance of CT-based multi-patient atlases for automated atlas based auto-contouring has been demonstrated, and can be adopted for clinical use in planning of local regional breast and high-risk prostate radiotherapy

Safety and resiliency in action: Integrating risk management into local development

Directory of Open Access Journals (Sweden)

Ebay Jorge S.

2013-01-01

Full Text Available This paper examines the efforts of the local government unit (LGU of San Jose de Buenavista, in the Province of Antique in central Philippines to manage risks associated with multiple hazards to protect the people, their livelihoods and local development gains. More specifically, it analyzes the process of pursuing risk management objectives vis-a-vis national and international disaster risk reduction and management (DRRM norms, without loosing sight of local contextual realities that directly influence people’s vulnerabilities and capacities. Risk management initiatives in the LGU revolve around four key areas namely disaster prevention and mitigation, disaster preparedness, emergency response, and recovery and rehabilitation. Binding these initiatives are actions that integrate governance mechanisms with scientific data and sectoral and community participation to develop a comprehensive plan of action and standard operating procedures that will serve as guideposts in the process of building a safer community. The experience of San Jose de Buenavista also suggests that cost saving strategies an be replicated by communities and organizations that have financial limitations to pursue DRRM objectives. This paper contends that risk management is a fundamental development strategy to pursue local development goals and to sustain efforts to protect development gains in the long run. This can be done using a combination of governance, risk assessment, knowledge management, vulnerability reduction and preparedness strategies. Local leadership, people’s participation, environmental resource management and continuous capability building are key elements of the process. Ultimately, risk management must be mainstreamed into local development to develop community resiliency.

The prognostic value of expression of HIF1α, EGFR and VEGF-A, in localized prostate cancer for intermediate- and high-risk patients treated with radiation therapy with or without androgen deprivation therapy

Directory of Open Access Journals (Sweden)

Weber Damien C

2012-04-01

Full Text Available Abstract Purpose Androgens stimulate the production of hypoxia-inducible factor (HIF1α and ultimately vascular endothelial growth factor (VEGF-A. Additionally, epithelial growth factor (EGF mediates HIF1α production. Carbonic anhydrase IX (CAIX expression is associated with tumor cell hypoxia in a variety of malignancies. This study assesses the prognostic relation between HIF1α, VEGF-A, EGF Receptor and CAIX expression by immunochemistry in diagnostic samples of patients with intermediate- and high-risk localized prostate cancer treated with radiation therapy, with or without androgen deprivation therapy (ADT. Materials and methods Between 1994 and 2004, 103 prostate cancer patients (mean age, 68.7 ± 6.2, with prostate cancer (mean PSA, 13.3 ± 3.7, were treated with radiation therapy (RT, median dose, 74 Gy. Fifty seven (55.3% patients received ADT (median duration, 6 months; range, 0 – 24. Median follow-up was 97.6 months (range, 5.9 – 206.8. Results Higher EGFR expression was significantly (p = 0.04 correlated with higher Gleason scores. On univariate analysis, HIF1α nuclear expression was a significant (p = 0.02 prognostic factor for biological progression-free survival (bPFS. A trend towards significance (p = 0.05 was observed with EGFR expression and bPFS. On multivariate analysis, low HIF1α nuclear (p = 0.01 and high EGFR (p = 0.04 expression remained significant adverse prognostic factors. Conclusions Our study suggests that high nuclear expression of HIF1α and low EGFR expression in diagnostic biopsies of prostate cancer patients treated with RT ± ADT is associated with a good prognosis.

Risk factor management: antiatherogenic therapies.

Science.gov (United States)

Gielen, Stephan; Sandri, Marcus; Schuler, Gerhard; Teupser, Daniel

2009-08-01

Despite the advances in interventional techniques, the management of stable atherosclerosis remains the domain of optimal guideline-oriented therapy. Recent studies on the effects of aggressive lipid lowering on atheroma volume changes using intravascular ultrasound indicate that it is possible to achieve atherosclerosis regression by reaching low-density lipoprotein (LDL) levels less than 75 mg/dl. The pleiotropic anti-inflammatory effects of statins contribute to the reduction of cardiovascular (CV) event observed with aggressive lipid lowering. As a second important strategy to prevent disease progression, lifestyle changes with regular physical exercise are capable of halting the atherosclerotic process and reducing angina symptoms and CV events. Optimal medical therapy, a healthy lifestyle with regular physical exercise, and coronary interventions are not mutually exclusive treatment strategies. Over the last few decades, both have proved to be effective in significantly reducing the CV mortality in the Western world. However, risk factor modification contributed to at least half the effect in the reduction of CV mortality. This figure provides an estimate of what could be achieved if we were to take risk factor modification more seriously - especially in the acute care setting. The knowledge is there: today we have a better understanding on how to stop progression and even induce regression of atherosclerosis. Much research still needs to be done and will be done. In the meantime, however, our primary focus should lie in implementing what is already known. In addition, it is essential not just to treat CV risk factors, but also to treat them to achieve the target values as set by the guidelines of European Society of Cardiology.

Radiation-Induced Leukemia at Doses Relevant to Radiation Therapy: Modeling Mechanisms and Estimating Risks

Science.gov (United States)

Shuryak, Igor; Sachs, Rainer K.; Hlatky, Lynn; Mark P. Little; Hahnfeldt, Philip; Brenner, David J.

2006-01-01

Because many cancer patients are diagnosed earlier and live longer than in the past, second cancers induced by radiation therapy have become a clinically significant issue. An earlier biologically based model that was designed to estimate risks of high-dose radiation induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks. Methods: To extend the model to radiation-induced leukemias, we analyzed in addition to cellular initiation, inactivation, and proliferation a repopulation mechanism specific to the hematopoietic system: long-range migration through the blood stream of hematopoietic stem cells (HSCs) from distant locations. Parameters for the model were derived from HSC biologic data in the literature and from leukemia risks among atomic bomb survivors v^ ho were subjected to much lower radiation doses. Results: Proliferating HSCs that migrate from sites distant from the high-dose region include few preleukemic HSCs, thus decreasing the high-dose leukemia risk. The extended model for leukemia provides risk estimates that are consistent with epidemiologic data for leukemia risk associated with radiation therapy over a wide dose range. For example, when applied to an earlier case-control study of 110000 women undergoing radiotherapy for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for leukemia among women who received a large inhomogeneous fractionated external beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11 cases observed). As a corresponding example for brachytherapy, the predicted ERR of 0.80 among women who received an inhomogeneous low

Systematic review of innovative ablative therapies for the treatment of locally advanced pancreatic cancer

NARCIS (Netherlands)

Rombouts, S. J. E.; Vogel, J. A.; van Santvoort, H. C.; van Lienden, K. P.; van Hillegersberg, R.; Busch, O. R. C.; Besselink, M. G. H.; Molenaar, I. Q.

2015-01-01

BackgroundLocally advanced pancreatic cancer (LAPC) is associated with a very poor prognosis. Current palliative (radio)chemotherapy provides only a marginal survival benefit of 2-3 months. Several innovative local ablative therapies have been explored as new treatment options. This systematic

Issues concerning the use of hormone replacement therapy and risk of fracture: a population-based, nested case-control study.

Science.gov (United States)

Corrao, Giovanni; Zambon, Antonella; Nicotra, Federica; Conti, Valentino; Nappi, Rossella E; Merlino, Luca

2008-01-01

To investigate the effect of duration, how recently it has been used, and age at start of hormone replacement therapy (HRT) and the risk of bone fracture. A population-based, nested case-control study was conducted in Lombardia, Northern Italy. The 78,294 women aged 45-75 years who received at least one HRT prescription during 1998-2000 were followed until 2005. Cases were women who experienced bone fracture during follow-up. Up to six controls were randomly selected for each case from the cohort after matching for age and date of cohort entry. The odds ratio of fracture associated with the use of HRT was estimated by conditional logistic regression. One thousand one hundred and seventy-four cases and 6760 controls were included. Compared with women who took HRT for less than 2 months, those who were treated for more than 20 months had an odds ratio (OR) of 0.80 (95% confidence interval 0.65, 0.99). This risk reduction was still significant among current HRT users (OR 0.71, 95% CI 0.55, 0.90) and in women who began therapy at the age of 55-65 years (OR 0.63, 95% CI 0.42, 0.94) or 65-75 years (OR 0.56, 95% CI 0.32, 0.99). There was no statistical evidence of a protective effect for women who had stopped treatment more than 6 months previously or those who began HRT at the age of 45-55 years. HRT should be continued for long periods to achieve an optimal protection from fracture. The fracture reducing potential of HRT seems to disappear after a few months without treatment and might mainly act in women who begin therapy at older age.

Traditional and Local Knowledge Practices for Disaster Risk Reduction in Northern Ghana

Directory of Open Access Journals (Sweden)

Nsioh Macnight Ngwese

2018-03-01

Full Text Available In order to deal with recurrent disasters, like floods and droughts coupled with the limited adaptive capacity, in the semiarid regions of Northern Ghana, local communities have no choice but to apply traditional and local knowledge practices. This study seeks to identify such practices employed in selected rural communities in Northern Ghana and to investigate their effectiveness. Data were collected through key informant interviews, household questionnaire surveys, focus group discussions, and participant observations. The findings indicated that although diverse practices were applied to predict and manage local disaster events, skepticism prevailed among locals toward these practices regarding their effectiveness. Due to the lack of science-based tools and systems for disaster prediction and management, local communities continually depended on these knowledge systems and practices. Integrating local and traditional disaster risk reduction (DRR efforts into modern scientific knowledge should be encouraged in order to reduce the vulnerability of local communities to disasters with thorough effectiveness evaluation protocols.

Laser therapy for onychomycosis in patients with diabetes at risk for foot complications : study protocol for a randomized, double-blind, controlled trial (LASER-1)

NARCIS (Netherlands)

Nijenhuis-Rosien, Leonie; Kleefstra, Nanne; Wolfhagen, Maurice J.; Groenier, Klaas H.; Bilo, Henk J. G.; Landman, Gijs W. D.

2015-01-01

Background: In a sham-controlled double-blind trial, we aim to establish the efficacy and safety of the local application of laser therapy in patients with diabetes, onychomycosis and risk factors for diabetes-related foot complications. Onychomycosis leads to thickened and distorted nails, which in

Depression and Anxiety Prevention Based on Cognitive Behavioral Therapy for At-Risk Adolescents: A Meta-Analytic Review

Directory of Open Access Journals (Sweden)

Sanne P. A. Rasing

2017-06-01

Full Text Available Depression and anxiety disorders are among the most common mental disorders during adolescence. During this life phase, the incidence of these clinical disorders rises dramatically, and even more adolescents suffer from symptoms of depression or anxiety that are just below the clinical threshold. Both clinical and subclinical levels of depression or anxiety symptoms are related to decreased functioning in various areas, such as social and academic functioning. Prevention of depression and anxiety in adolescents is therefore imperative. We conducted a meta-analytic review of the effects of school-based and community-based prevention programs that are based on cognitive behavioral therapy with the primary goal preventing depression, anxiety, or both in high risk adolescents. Articles were obtained by searching databases and hand searching reference lists of relevant articles and reviews. The selection process yielded 32 articles in the meta-analyses. One article reported on two studies and three articles reported on both depression and anxiety. This resulted in a total of 36 studies, 23 on depression and 13 on anxiety. For depression prevention aimed at high risk adolescents, meta-analysis showed a small effect of prevention programs directly after the intervention, but no effect at 3–6 months and at 12 months follow-up. For anxiety prevention aimed at high risk adolescents, no short-term effect was found, nor at 12 months follow-up. Three to six months after the preventive intervention, symptoms of anxiety were significantly decreased. Although effects on depression and anxiety symptoms were small and temporary, current findings cautiously suggest that depression and anxiety prevention programs based on CBT might have small effects on mental health of adolescents. However, it also indicates that there is still much to be gained for prevention programs. Current findings and possibilities for future research are discussed in order to further

Surging Seas Risk Finder: A Tool for Local-Scale Flood Risk Assessments in Coastal Cities

Science.gov (United States)

Kulp, S. A.; Strauss, B.

2015-12-01

Local decision makers in coastal cities require accurate, accessible, and thorough assessments of flood exposure risk within their individual municipality, in their efforts to mitigate against damage due to future sea level rise. To fill this need, we have developed Climate Central's Surging Seas Risk Finder, an interactive data toolkit which presents our sea level rise and storm surge analysis for every coastal town, city, county, and state within the USA. Using this tool, policy makers can easily zoom in on their local place of interest to receive a detailed flood risk assessment, which synthesizes a wide range of features including total population, socially vulnerable population, housing, property value, road miles, power plants, schools, hospitals, and many other critical facilities. Risk Finder can also be used to identify specific points of interest in danger of exposure at different flood levels. Additionally, this tool provides localized storm surge probabilities and sea level rise projections at tidal gauges along the coast, so that users can quickly understand the risk of flooding in their area over the coming decades.

Outcome of three-dimensional conformal radiation therapy and intensity-modulated radiation therapy for inoperable locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Lu Ningning; Jin Jing; Li Yexiong; Yu Zihao; Liu Xinfan; Wang Weihu; Wang Shulian; Song Yongwen; Liu Yuping

2009-01-01

Objective: To evaluate the outcome of radiotherapy for locally advanced pancreatic cancer. Methods: From January 2000 to December 2007, 41 patients with inoperable locally advanced (stage III) pancreatic cancer were treated with three-dimensional conformal radiation therapy(3DCRT) or intensity-modulated radiation therapy (IMRT). Among these patients, 30 received concurrent radio-chemo-therapy. Results: The median survival time(MST) and 1-year overall survival were 9.2 months and 23%. Patients with pretreatment KPS ≥ 80, no regional lymph nodes metastasis, and CR/PR after radiotherapy had better prognosis. The corresponding MSTs were 11.1 months vs 5.8 months (χ 2 =7.50, P=0.006), 10.8 months vs 6.5 months(χ 2 =5.67, P=0.017), and 19.5 months vs 9.1 months (χ 2 =7.28, P=0.007), respectively. Concurrent radio-chemotherapy tended to improve the overall survival(χ 2 =3.25, P=0.072). After radiotherapy, 18 patients had clinical benefit response, mainly being abdominal pain relief. Neither grade 4 hematologic nor grade 3 non-hematologic toxicities were observed. Conclusions: For patients with locally advanced pancreatic cancer, both 3DCRT and IMRT are effective in alleviation of disease-related symptoms. Patients with better performance status before treatment, no regional lymph nodes metastasis, and better response to radiotherapy may have better prognosis. Concurrent radio-chemotherapy trend to improve overall survival when compared with radiotherapy alone. (authors)

Travel and biologic therapy: travel-related infection risk, vaccine response and recommendations.

Science.gov (United States)

Hall, Victoria; Johnson, Douglas; Torresi, Joseph

2018-01-01

Biologic therapy has revolutionized the management of refractory chronic autoimmune and auto-inflammatory disease, as well as several malignancies, providing rapid symptomatic relief and/or disease remission. Patients receiving biologic therapies have an improved quality of life, facilitating travel to exotic destinations and potentially placing them at risk of a range of infections. For each biologic agent, we review associated travel-related infection risk and expected travel vaccine response and effectiveness. A PUBMED search [vaccination OR vaccine] AND/OR ['specific vaccine'] AND/OR [immunology OR immune response OR response] AND [biologic OR biological OR biologic agent] was performed. A review of the literature was performed in order to develop recommendations on vaccination for patients in receipt of biologic therapy travelling to high-risk travel destinations. There is a paucity of literature in this area, however, it is apparent that travel-related infection risk is increased in patients on biologic therapy and when illness occurs they are at a higher risk of complication and hospitalization. Patients in receipt of biologic agents are deemed as having a high level of immunosuppression-live vaccines, including the yellow fever vaccine, are contraindicated. Inactivated vaccines are considered safe; however, vaccine response can be attenuated by the patient's biologic therapy, thereby resulting in reduced vaccine effectiveness and protection. Best practice requires a collaborative approach between the patient's primary healthcare physician, relevant specialist and travel medicine expert, who should all be familiar with the immunosuppressive and immunomodulatory effects resulting from the biologic therapies. Timing of vaccines should be carefully planned, and if possible, vaccination provided well before established immunosuppression.

Magnetic Resonance Imaging-Based Target Volume Delineation in Radiation Therapy Treatment Planning for Brain Tumors Using Localized Region-Based Active Contour

International Nuclear Information System (INIS)

Aslian, Hossein; Sadeghi, Mahdi; Mahdavi, Seied Rabie; Babapour Mofrad, Farshid; Astarakee, Mahdi; Khaledi, Navid; Fadavi, Pedram

2013-01-01

Purpose: To evaluate the clinical application of a robust semiautomatic image segmentation method to determine the brain target volumes in radiation therapy treatment planning. Methods and Materials: A local robust region-based algorithm was used on MRI brain images to study the clinical target volume (CTV) of several patients. First, 3 oncologists delineated CTVs of 10 patients manually, and the process time for each patient was calculated. The averages of the oncologists’ contours were evaluated and considered as reference contours. Then, to determine the CTV through the semiautomatic method, a fourth oncologist who was blind to all manual contours selected 4-8 points around the edema and defined the initial contour. The time to obtain the final contour was calculated again for each patient. Manual and semiautomatic segmentation were compared using 3 different metric criteria: Dice coefficient, Hausdorff distance, and mean absolute distance. A comparison also was performed between volumes obtained from semiautomatic and manual methods. Results: Manual delineation processing time of tumors for each patient was dependent on its size and complexity and had a mean (±SD) of 12.33 ± 2.47 minutes, whereas it was 3.254 ± 1.7507 minutes for the semiautomatic method. Means of Dice coefficient, Hausdorff distance, and mean absolute distance between manual contours were 0.84 ± 0.02, 2.05 ± 0.66 cm, and 0.78 ± 0.15 cm, and they were 0.82 ± 0.03, 1.91 ± 0.65 cm, and 0.7 ± 0.22 cm between manual and semiautomatic contours, respectively. Moreover, the mean volume ratio (=semiautomatic/manual) calculated for all samples was 0.87. Conclusions: Given the deformability of this method, the results showed reasonable accuracy and similarity to the results of manual contouring by the oncologists. This study shows that the localized region-based algorithms can have great ability in determining the CTV and can be appropriate alternatives for manual approaches in brain cancer

Magnetic Resonance Imaging-Based Target Volume Delineation in Radiation Therapy Treatment Planning for Brain Tumors Using Localized Region-Based Active Contour

Energy Technology Data Exchange (ETDEWEB)

Aslian, Hossein [Department of Medical Radiation, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Sadeghi, Mahdi [Agricultural, Medical and Industrial Research School, Karaj (Iran, Islamic Republic of); Mahdavi, Seied Rabie [Department of Medical Physics, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Babapour Mofrad, Farshid [Department of Medical Radiation, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Astarakee, Mahdi, E-mail: M-Astarakee@Engineer.com [Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Khaledi, Navid [Department of Medical Radiation, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Fadavi, Pedram [Department of Radiation Oncology, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2013-09-01

Purpose: To evaluate the clinical application of a robust semiautomatic image segmentation method to determine the brain target volumes in radiation therapy treatment planning. Methods and Materials: A local robust region-based algorithm was used on MRI brain images to study the clinical target volume (CTV) of several patients. First, 3 oncologists delineated CTVs of 10 patients manually, and the process time for each patient was calculated. The averages of the oncologists’ contours were evaluated and considered as reference contours. Then, to determine the CTV through the semiautomatic method, a fourth oncologist who was blind to all manual contours selected 4-8 points around the edema and defined the initial contour. The time to obtain the final contour was calculated again for each patient. Manual and semiautomatic segmentation were compared using 3 different metric criteria: Dice coefficient, Hausdorff distance, and mean absolute distance. A comparison also was performed between volumes obtained from semiautomatic and manual methods. Results: Manual delineation processing time of tumors for each patient was dependent on its size and complexity and had a mean (±SD) of 12.33 ± 2.47 minutes, whereas it was 3.254 ± 1.7507 minutes for the semiautomatic method. Means of Dice coefficient, Hausdorff distance, and mean absolute distance between manual contours were 0.84 ± 0.02, 2.05 ± 0.66 cm, and 0.78 ± 0.15 cm, and they were 0.82 ± 0.03, 1.91 ± 0.65 cm, and 0.7 ± 0.22 cm between manual and semiautomatic contours, respectively. Moreover, the mean volume ratio (=semiautomatic/manual) calculated for all samples was 0.87. Conclusions: Given the deformability of this method, the results showed reasonable accuracy and similarity to the results of manual contouring by the oncologists. This study shows that the localized region-based algorithms can have great ability in determining the CTV and can be appropriate alternatives for manual approaches in brain cancer.

Locally challenging osteo- and chondrogenic tumors of the axial skeleton: results of combined proton and photon radiation therapy using three-dimensional treatment planning

Energy Technology Data Exchange (ETDEWEB)

Hug, Eugen B; Fitzek, Markus M; Liebsch, Norbert J; Munzenrider, John E

1995-02-01

Purpose: Tumors of the axial skeleton are at high risk for local failure. Total surgical resection is rarely possible. Critical normal tissues limit the efficacy of conventional photon therapy. This study reviews our experience of using combined high dose proton and photon radiation therapy following three-dimensional (3D) treatment planning. Methods and Materials: Between December 1980 and September 1992, 47 patients were treated at the Massachusetts General Hospital and Harvard Cyclotron Laboratory for primary or recurrent chordomas and chondrosarcomas (group 1, 20 patients), osteogenic sarcomas (group 2, 15 patients) and giant cell tumors, osteo- or chondroblastomas (group 3, 12 patients). Radiation treatment was given postoperatively in 23 patients, pre- and postoperatively in 17 patients, and 7 patients received radiation therapy as definitive treatment modality following biopsy only. The proton radiation component was delivered using a 160 MeV proton beam and the photon component using megavoltage photons up to 23 MV energy with 1.8-2.0 Cobalt Gray Equivalent (CGE) per fraction, once a day. Total external beam target dose ranged from 55.3 CGE to 82.0 CGE with mean target doses of 73.9 CGE (group 1), 69.8 CGE (group 2), and 61.8 CGE (group 3). Results: Group 1 (chordoma and chondrosarcoma): Five of 14 patients (36%) with chordoma recurred locally, and 2 out of 5 patients developed distant metastasis, resulting in 1 death from disease. A trend for improved local control was noted for primary vs. recurrent tumors, target doses > 77 CGE and gross total resection. All patients with chondrosarcoma achieved and maintained local control and disease-free status. Five-year actuarial local control and overall survival rates were 53% and 50% for chordomas and 100% and 100% for chondrosarcomas, respectively. Group 2 (osteogenic sarcoma): Three of 15 patients (20%) never achieved local control and died within 6 months of completion of radiation treatment. Only 1 out of 12

Comparison of local metronidazole and a local antiseptic in the treatment of bacterial vaginosis.

Science.gov (United States)

Novakov Mikic, Aleksandra; Budakov, Dragan

2010-07-01

Bacterial vaginosis (BV) is characterized by a mixed flora of pathogenic anaerobic bacteria and associated with risks of pathologic conditions. In the present study, therapy with a local antiseptic spray (octenidine hydrochloride/phenoxyethanol, OHP) for 7 or 14 days is compared against the standard local therapy of BV (metronidazole) in a Serbian patient population. As much as 450 women were treated in groups with either 7 days metronidazole vaginal tablets, 7 days OHP, or 14 days OHP. Control smears were taken after each treatment period. In total, 63.2% of the women were without indications of BV after therapy (metronidazole: 61.0%, OHP 7 days: 57.6%, and OHP 14 days: 71.0%). Significantly fewer women were affected from infections after treatment with 14 days OHP compared to OHP for 7 days. Octenidine hydrochloride/phenoxyethanol spray was as effective as the standard therapy with metronidazole. Patients stated that OHP was more comfortable, easier to apply, and side effects were lesser.

The impact of a focally positive resection margin on the local control in patients treated with breast-conserving therapy

International Nuclear Information System (INIS)

Park, Seho; Park, Hyung-Seok; Kim, Seung-ll; Koo, Ja-Seung; Park, Byeong-Woo; Lee, Kyong-Sik

2011-01-01

The aim of the study was to investigate the parameters affecting positive margin and the impact of positive margin on outcomes after breast-conserving therapy in patients with breast cancer. Characteristics and survival of 705 patients attempted breast-conserving therapy between January 1994 and December 2004 were retrospectively analyzed using χ 2 tests, the Kaplan-Meier methods and multivariate analyses. Ninety-five (13.5%) showed positive margins at initial resection. Among them, 28 (4.0%) had negative margin on the initial frozen section; however, they finally turned out a focally positive margin with intraductal carcinoma on the permanent pathology. Positive margin at initial resection was significantly associated with lobular histology (P=0.001), four or more involved lymph nodes (P=0.015) and the presence of extensive intraductal component (P<0.001). A focally positive margin did not influence local (P=0.250; 95% confidence interval, 0.612-6.592) or regional failure (P=0.756; 95% confidence interval, 0.297-5.311). Patients with a focally positive margin showed an advanced nodal stage and received a higher dose of irradiation and more systemic therapy. Nodal involvements were the most significant factor for locoregional failure. Although the achievement of negative margins is the best way to reduce local failure, patients with a focally positive margin and favorable risk factors such as node negativity and older age could have an option of close follow-up with adequate boost irradiation and adjuvant therapy instead of conversion to total mastectomy. (author)

Defining the implant treatment volume for patients with low risk prostate cancer: does the anterior base need to be treated?

International Nuclear Information System (INIS)

D'Amico, Anthony V.; Davis, Ann; Vargas, Sara O.; Renshaw, Andrew A.; Jiroutek, Michael; Richie, Jerome P.

1999-01-01

Purpose: An increased incidence of acute urinary retention has been reported after interstitial prostate radiation therapy when the anterior base of the prostate gland receives 100% of the prescription dose. The frequency of prostate cancer in this location as a function of the pre-treatment prostate specific antigen (PSA), biopsy Gleason score, and 1992 American Joint Commission on Cancer Staging (AJCC) was determined. Methods and Materials: One hundred four men treated at the Brigham and Women's Hospital with radical prostatectomy for clinically localized prostate cancer between 1995-1996 comprised the study population. Prostatectomy specimens were whole mounted and the location of each tumor foci enumerated. Results: Of 269 foci of prostate cancer found in 39 low-risk prostate cancer patients (PSA 1c,2a ), a single focus (0.37%) was noted in the anterior base. Conversely, 20/355 (5.6%) and 18/251 (7.2%) tumor foci were noted in the anterior base in 43 patients with intermediate risk and 24 patients with high-risk disease, respectively. Conclusions: A new definition of the treatment volume excluding the anterior base for low-risk prostate cancer patients may be justified

Benefits and Risks of Antithrombotic Therapy in Essential Thrombocythemia: A Systematic Review.

Science.gov (United States)

Chu, Derek K; Hillis, Christopher M; Leong, Darryl P; Anand, Sonia S; Siegal, Deborah M

2017-08-01

Patients with essential thrombocythemia (ET) are at high risk for both thrombosis and hemorrhage. To evaluate the risks and benefits of antithrombotic therapy in adults with ET. Multiple databases, including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, through 4 March 2017. Randomized and observational studies of antiplatelet or anticoagulant therapy, published in any language and reporting thrombotic or hemorrhagic events. Two reviewers independently extracted data, assessed risk of bias, and graded certainty of evidence. No relevant randomized trials were identified. Twenty-four observational studies (18 comparative and 6 single-group) involving 6153 patients followed for 31 711 patient-years were reviewed; most were deemed to have high risk of bias. Most patients receiving antiplatelet therapy (3613 of 4527 [80%]) received low-dose aspirin (50 to 150 mg/d); 914 (20%) received high-dose aspirin (300 to 600 mg/d), dipyridamole, or other agents. Overall, findings were inconsistent and imprecise. The reported incidence rates of thrombosis, any bleeding, and major bleeding without antiplatelet therapy ranged from 5 to 110 (median, 20), from 3 to 39 (median, 8), and from 2 to 53 (median, 6) cases per 1000 patient-years, respectively. The reported relative risks for thrombosis, any bleeding, and major bleeding with antiplatelet therapy compared with none ranged from 0.26 to 3.48 (median, 0.74), from 0.48 to 11.04 (median, 1.95), and from 0.48 to 5.17 (median, 1.30), respectively. Certainty of evidence was rated low or very low for all outcomes. No randomized trials, no extractable data on anticoagulants, lack of uniform bleeding definitions, and systematic reporting of outcomes. Available evidence about the risk-benefit ratio of antiplatelet therapy in adults with ET is highly uncertain. Regional Medical Associates. (PROSPERO: CRD42015027051).

[Effects of periodontal mechanical therapy with local and systemic drugs on carotid artery and serum high-sensitivity C-reactive protein in rats with chronic periodontitis associated with atherosclerosis].

Science.gov (United States)

Ren, Xiuyun; Chang, Le; Yue, Zijie; Lin, Mu; Shi, Xuexue; Sun, Lili

2013-10-01

The aim of this study is to investigate the effects of serum high-sensitivity C-reactive protein (hsCRP) and the pathological changes in the carotid artery after periodontal mechanical therapy with local and systemic drugs in SD rats with chronic periodontitis (CP) associated with atherosclerosis (As). Thirty-five SD rats were randomly divided into two groups: control group (group A) and CP+As group (group B). Group B was further divided into the natural process group (B1), the periodontal mechanical treatment group (B2), the periodontal mechanical treatment plus local drugs group (B3), and the periodontal mechanical treatment plus local and systemic drugs group (B4). Each group comprised seven rats. Serum hsCRP levels were evaluated at baseline 1 week after the first periodontal therapy and 1, 3, and 5 weeks after the second periodontal therapy by enzyme linked immunosorbent assay (ELISA). The pathological lesion in the carotid artery plaque was stained with hematine and eosin. The levels of serum hsCRP in group B1 increased gradually as time passed and became significantly higher than that of the other groups five weeks after periodontal therapy (P periodontal therapy. After that, the levels of serum hsCRP decreased gradually but were still higher than that of group A (P periodontal therapy (P periodontal mechanical treatment results in acute, short-term, systemic inflammation and might increase the risk of atherosclerosis in SD rats. However, the levels of serum hsCRP decreased gradually 3 to 5 weeks after therapy. With periodontal mechanical treatment, the benefits of local and systemic drugs are associated with improvement in atherosclerotic lesion progression.

Treatment outcome and risk analysis for cataract after radiotherapy of localized ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma

Energy Technology Data Exchange (ETDEWEB)

Park, Hee Hyun; Lee, Sea Won; Sung, Soo Yoon; Choi, Byung Oak [Dept. of Radiation Oncology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul, (Korea, Republic of)

2017-09-15

We retrospectively reviewed the results of radiotherapy for localized ocular adnexal MALT lymphoma (OAML) to investigate the risk factors of cataract. Sixty-seven patients with stage IE OAML treated with radiotherapy at Seoul St. Mary’s Hospital from 2001 to 2016 were included. Median treatment dose was 30 Gy. Lens protection was done in 52 (76%) patients. Radiation therapy (RT) extent was as follows: superficial (82.1%), tumor mass (4.5%), and entire orbital socket (13.4%). The risk factors for symptomatic cataract were analyzed using the Cox proportional hazard model. Median follow-up time was 50.9 months (range, 1.9 to 149.4 months). All patients were alive at the time of analysis. There were 7 recurrences and there was no local recurrence. Median time to recurrence was 40.4 months. There were 14 cases of symptomatic cataract. Dose >30 Gy had hazard ratio of 3.47 for cataract (p = 0.026). Omitting lens protection showed hazard ratio of 4.10 (p = 0.008). RT achieves excellent local control of ocular MALT lymphoma. Consideration of RT-related factors such as lens protection and radiation dose at the stage of RT planning may reduce the risk of RT-induced cataract after radiotherapy.

Nursing care for patients with local recurrent rectal cancer after CT-guided 125I seed implantation therapy

International Nuclear Information System (INIS)

Yuan Li; Wei Fan; Ren Caifeng; Tu Mingmei; Qian Guixiang

2010-01-01

Objective: To discuss the nursing care strategy for patients with local recurrent rectal cancer who has been treated with CT-guided 125 I seed implantation therapy. Methods: Twenty patients with local recurrent rectal cancer received a series of nursing interventions, including comfort care and pain care. The clinical results were observed and analyzed. Results: The therapy was smoothly accomplished in all patients. The pain was remarkably relived and the anxiety was alleviated. No displacement of implanted 125 I seed occurred. Conclusion: For patients with local recurrent rectal cancer occurred after CT-guided 125 I seed implantation therapy, careful nursing can effectively relieve the pain and anxiety feeling,and the living quality can also be markedly improved. (authors)

Phase 2 Study of Temozolomide-Based Chemoradiation Therapy for High-Risk Low-Grade Gliomas: Preliminary Results of Radiation Therapy Oncology Group 0424

Energy Technology Data Exchange (ETDEWEB)

Fisher, Barbara J., E-mail: barbara.fisher@lhsc.on.ca [London Regional Cancer Program, London, Ontario (Canada); Hu, Chen [Radiation Therapy Oncology Group-Statistical Center, Philadelphia, Pennsylvania (United States); Macdonald, David R. [London Regional Cancer Program, London, Ontario (Canada); Lesser, Glenn J. [Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina (United States); Coons, Stephen W. [Barrow Neurological Institute, Phoenix, Arizona (United States); Brachman, David G. [Arizona Oncology Services Foundation, Phoenix, Arizona (United States); Ryu, Samuel [Henry Ford Hospital, Detroit, Michigan (United States); Werner-Wasik, Maria [Thomas Jefferson University Hospital Center, Philadelphia, Pennsylvania (United States); Bahary, Jean-Paul [Centre Hospitalier de l' Université de Montréal-Notre Dame, Montreal, Quebec (Canada); Liu, Junfeng [GCE Solutions, Inc., Bloomington, Illinois (United States); Chakravarti, Arnab [The Ohio State University, The James, Columbus, Ohio (United States); Mehta, Minesh [University of Maryland Medical Systems, Baltimore, Maryland (United States)

2015-03-01

Purpose: Radiation Therapy Oncology Group (RTOG) 0424 was a phase 2 study of a high-risk low-grade glioma (LGG) population who were treated with temozolomide (TMZ) and radiation therapy (RT), and outcomes were compared to those of historical controls. This study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months and a 20% improvement in 3-year overall survival (OS) rate from 54% to 65% at a 10% significance level (1-sided) and 96% power. Methods and Materials: Patients with LGGs with 3 or more risk factors for recurrence (age ≥40 years, astrocytoma histology, bihemispherical tumor, preoperative tumor diameter of ≥6 cm, or a preoperative neurological function status of >1) were treated with RT (54 Gy in 30 fractions) and concurrent and adjuvant TMZ. Results: From 2005 to 2009, 129 evaluable patients (75 males and 54 females) were accrued. Median age was 49 years; 91% had a Zubrod score of 0 or 1; and 69%, 25%, and 6% of patients had 3, 4, and 5 risk factors, respectively. Patients had median and minimum follow-up examinations of 4.1 years and 3 years, respectively. The 3-year OS rate was 73.1% (95% confidence interval: 65.3%-80.8%), which was significantly improved compared to that of prespecified historical control values (P<.001). Median survival time has not yet been reached. Three-year progression-free survival was 59.2%. Grades 3 and 4 adverse events occurred in 43% and 10% of patients, respectively. One patient died of herpes encephalitis. Conclusions: The 3-year OS rate of 73.1% for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls (P<.001) and the study-hypothesized rate of 65%.

Breast conservation therapy based on liberal selection criteria and less extensive surgery. Analysis of cases with positive margins

International Nuclear Information System (INIS)

Amemiya, Atsushi; Kondo, Makoto

1999-01-01

The relationship between the margin status and the risk of in-breast recurrence (IBR) is an important consideration in patients treated with breast conservation therapy but has not been defined adequately. To address this issue, 1533 clinical stage I and II patients who completed irradiation therapy between 1983 and 1998 were evaluated. Only selection criterion was whether she could be satisfied with cosmesis after lumpectomy. Size and location of the tumor, nodal status, histology and age were not primary consideration. The tumor was excised in such a way to obtain macroscopically clear margins. The breast was treated with 50 Gy of external irradiation but without boost. Margins were evaluated by serially sectioning of the specimen and the margin was judged positive only when cancer cells were present on the inked surface. Margins were also evaluated by scratch cytology. Seventy two IBR were experienced within 5 years. Only age and margin status were found to be independent risk factors. Five-year IBR rate with negative and positive margins was 3.7% and 10.0%, respectively. In patients with positive margins, number of positive site and positive cytology were independent risk factor for IBR. IBR rate among patients with focally involved margins by non-comedo, comedo and invasive ca, was 0.0%, 3.5%, and 8.7%, respectively. IBR rate in more than focal involvement by non-comedo, comedo, and invasive ca, was 4.0%, 33.0% and 30.0%, respectively. If histologically positive margin was also positive cytologically, IBR was 14.8%, whereas only 3.6% if negative cytologically. Even with liberal patient selection and less extensive local treatment, adequate local control can be obtained, provided that margins are histologically and/or cytologically negative. Focal margin involvement by DCIS or more than focal involvement by non-comedo type DCIS does not jeopardize local control. More than focal involvement by comedo DCIS or involvement by invasive ca results in high IBR rate

Magnetic resonance guided focalized ultrasound thermo-ablation: A promising oncologic local therapy

International Nuclear Information System (INIS)

Iannessi, A.; Doyen, J.; Leysalle, A.; Thyss, A.

2014-01-01

Pain management of bone metastases is usually made using systemic and local therapy. Even though radiations are nowadays the gold standard for painful metastases, innovations regarding minimally invasive treatment approaches have been developed because of the existing non-responder patients [1]. Indeed, cementoplasty and thermo-ablations like radiofrequency or cryotherapy have shown to be efficient on pain [2-4]. Among thermo-therapy, magnetic resonance guided focalized ultrasound is now a new non-invasive weapon for bone pain palliation. (authors)

Adjuvant radiochemotherapy in patients with locally advanced high-risk cervical cancer

Energy Technology Data Exchange (ETDEWEB)

Heinzelmann, F.; Henke, G.; Grafenstein, M. von; Weidner, N.; Paulsen, F.; Bamberg, M.; Weinmann, M. [Tuebingen Univ. (Germany). Dept. of Radiation Oncology; Staebler, A. [Tuebingen Univ. (Germany). Div. of Gynecologic Pathology; Brucker, S. [Tuebingen Univ. (Germany). Dept. of Gynecology

2012-07-15

Background and purpose: The aim of this retrospective study was to analyze the outcome of patients with locally advanced cervical carcinoma treated by adjuvant radiochemotherapy and to determine risk factors for local and distant relapse. Furthermore, acute and late effects of treatment were recorded. Patients and methods: A total of 72 patients with FIGO stages I-III cervical carcinoma were treated by radical hysterectomy, pelvic lymphadenectomy, and postoperative radiochemotherapy. Only patients with positive pelvic lymph nodes, parametrial involvement, positive margins, or tumor bulk were eligible. Patients were irradiated with a standard pelvic field (50.4 Gy in 28 fractions). The majority of patients received platinum-based chemotherapy. Results: After a median follow-up of 37 months, estimated 1-, 2-, and 4-year disease-free survival (DFS) and overall survival (OS) rates were 89%, 80%, 68% and 95%, 88%, 76%, respectively. Nine of the 72 patients had pelvic recurrences including only 1 isolated local failure; 23 of the 72 patients presented with distant relapse. The majority of relapses occurred within the first 3 years after adjuvant treatment. The number of positive pelvic lymph nodes (> 1) was the strongest prognostic factor for DFS. Treatment was well tolerated with transient acute hematologic ({proportional_to}30%) and gastrointestinal ({proportional_to}30%) grade 3 toxicity. Small bowel obstruction ({proportional_to}6%) was the only important late sequelae. Conclusion: Adjuvant radiochemotherapy in patients with advanced cervical cancer and several risk factors is highly effective to prevent local relapse. Future efforts to improve outcome should be placed on improvement of systemic control especially in subgroups with high-risk features for distant relapse. Combined treatment was well tolerated with moderate acute and late toxicity. (orig.)

SU-D-BRA-04: Computerized Framework for Marker-Less Localization of Anatomical Feature Points in Range Images Based On Differential Geometry Features for Image-Guided Radiation Therapy

International Nuclear Information System (INIS)

Soufi, M; Arimura, H; Toyofuku, F; Nakamura, K; Hirose, T; Umezu, Y; Shioyama, Y

2016-01-01

Purpose: To propose a computerized framework for localization of anatomical feature points on the patient surface in infrared-ray based range images by using differential geometry (curvature) features. Methods: The general concept was to reconstruct the patient surface by using a mathematical modeling technique for the computation of differential geometry features that characterize the local shapes of the patient surfaces. A region of interest (ROI) was firstly extracted based on a template matching technique applied on amplitude (grayscale) images. The extracted ROI was preprocessed for reducing temporal and spatial noises by using Kalman and bilateral filters, respectively. Next, a smooth patient surface was reconstructed by using a non-uniform rational basis spline (NURBS) model. Finally, differential geometry features, i.e. the shape index and curvedness features were computed for localizing the anatomical feature points. The proposed framework was trained for optimizing shape index and curvedness thresholds and tested on range images of an anthropomorphic head phantom. The range images were acquired by an infrared ray-based time-of-flight (TOF) camera. The localization accuracy was evaluated by measuring the mean of minimum Euclidean distances (MMED) between reference (ground truth) points and the feature points localized by the proposed framework. The evaluation was performed for points localized on convex regions (e.g. apex of nose) and concave regions (e.g. nasofacial sulcus). Results: The proposed framework has localized anatomical feature points on convex and concave anatomical landmarks with MMEDs of 1.91±0.50 mm and 3.70±0.92 mm, respectively. A statistically significant difference was obtained between the feature points on the convex and concave regions (P<0.001). Conclusion: Our study has shown the feasibility of differential geometry features for localization of anatomical feature points on the patient surface in range images. The proposed

SU-D-BRA-04: Computerized Framework for Marker-Less Localization of Anatomical Feature Points in Range Images Based On Differential Geometry Features for Image-Guided Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Soufi, M; Arimura, H; Toyofuku, F [Kyushu University, Fukuoka, Fukuoka (Japan); Nakamura, K [Hamamatsu University School of Medicine, Hamamatsu, Shizuoka (Japan); Hirose, T; Umezu, Y [Kyushu University Hospital, Fukuoka, Fukuoka (Japan); Shioyama, Y [Saga Heavy Ion Medical Accelerator in Tosu, Tosu, Saga (Japan)

2016-06-15

Purpose: To propose a computerized framework for localization of anatomical feature points on the patient surface in infrared-ray based range images by using differential geometry (curvature) features. Methods: The general concept was to reconstruct the patient surface by using a mathematical modeling technique for the computation of differential geometry features that characterize the local shapes of the patient surfaces. A region of interest (ROI) was firstly extracted based on a template matching technique applied on amplitude (grayscale) images. The extracted ROI was preprocessed for reducing temporal and spatial noises by using Kalman and bilateral filters, respectively. Next, a smooth patient surface was reconstructed by using a non-uniform rational basis spline (NURBS) model. Finally, differential geometry features, i.e. the shape index and curvedness features were computed for localizing the anatomical feature points. The proposed framework was trained for optimizing shape index and curvedness thresholds and tested on range images of an anthropomorphic head phantom. The range images were acquired by an infrared ray-based time-of-flight (TOF) camera. The localization accuracy was evaluated by measuring the mean of minimum Euclidean distances (MMED) between reference (ground truth) points and the feature points localized by the proposed framework. The evaluation was performed for points localized on convex regions (e.g. apex of nose) and concave regions (e.g. nasofacial sulcus). Results: The proposed framework has localized anatomical feature points on convex and concave anatomical landmarks with MMEDs of 1.91±0.50 mm and 3.70±0.92 mm, respectively. A statistically significant difference was obtained between the feature points on the convex and concave regions (P<0.001). Conclusion: Our study has shown the feasibility of differential geometry features for localization of anatomical feature points on the patient surface in range images. The proposed

Mindfulness-Based Therapies in the Treatment of Functional Gastrointestinal Disorders: A Meta-Analysis

Directory of Open Access Journals (Sweden)

Monique Aucoin

2014-01-01

Full Text Available Background. Functional gastrointestinal disorders are highly prevalent and standard treatments are often unsatisfactory. Mindfulness-based therapy has shown benefit in conditions including chronic pain, mood, and somatization disorders. Objectives. To assess the quality and effectiveness reported in existing literature, we conducted a meta-analysis of mindfulness-based therapy in functional gastrointestinal disorders. Methods. Pubmed, EBSCO, and Cochrane databases were searched from inception to May 2014. Study inclusion criteria included randomized, controlled studies of adults using mindfulness-based therapy in the treatment of functional gastrointestinal disorders. Study quality was evaluated using the Cochrane risk of bias. Effect sizes were calculated and pooled to achieve a summary effect for the intervention on symptom severity and quality of life. Results. Of 119 records, eight articles, describing seven studies, met inclusion criteria. In six studies, significant improvements were achieved or maintained at the end of intervention or follow-up time points. The studies had an unclear or high risk of bias. Pooled effects were statistically significant for IBS severity (0.59, 95% CI 0.33 to 0.86 and quality of life (0.56, 95% CI 0.47 to 0.79. Conclusion. Studies suggest that mindfulness based interventions may provide benefit in functional gastrointestinal disorders; however, substantial improvements in methodological quality and reporting are needed.

Incidence, Causative Mechanisms, and Anatomic Localization of Stroke in Pituitary Adenoma Patients Treated With Postoperative Radiation Therapy Versus Surgery Alone

Energy Technology Data Exchange (ETDEWEB)

Sattler, Margriet G.A., E-mail: g.a.sattler@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Vroomen, Patrick C. [Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Sluiter, Wim J. [Department of Endocrinology and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schers, Henk J. [Department of Primary and Community Care, Radboud University Nijmegen Medical Centre (Netherlands); Berg, Gerrit van den [Department of Endocrinology and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Wolffenbuttel, Bruce H.R. [Department of Endocrinology and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Bergh, Alphons C.M. van den [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Beek, André P. van [Department of Endocrinology and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)

2013-09-01

Purpose: To assess and compare the incidence of stroke and stroke subtype in pituitary adenoma patients treated with postoperative radiation therapy (RT) and surgery alone. Methods and Materials: A cohort of 462 pituitary adenoma patients treated between 1959 and 2008 at the University Medical Center Groningen in The Netherlands was studied. Radiation therapy was administered in 236 patients. The TOAST (Trial of ORG 10172 in Acute Stroke Treatment) and the Oxfordshire Community Stroke Project classification methods were used to determine causative mechanism and anatomic localization of stroke. Stroke incidences in patients treated with RT were compared with that observed after surgery alone. Risk factors for stroke incidence were studied by log–rank test, without and with stratification for other significant risk factors. In addition, the stroke incidence was compared with the incidence rate in the general Dutch population. Results: Thirteen RT patients were diagnosed with stroke, compared with 12 surgery-alone patients. The relative risk (RR) for stroke in patients treated with postoperative RT was not significantly different compared with surgery-alone patients (univariate RR 0.62, 95% confidence interval [CI] 0.28-1.35, P=.23). Stroke risk factors were coronary or peripheral artery disease (univariate and multivariate RR 10.4, 95% CI 4.7-22.8, P<.001) and hypertension (univariate RR 3.9, 95% CI 1.6-9.8, P=.002). There was no difference in TOAST and Oxfordshire classification of stroke. In this pituitary adenoma cohort 25 strokes were observed, compared with 16.91 expected (standard incidence ratio 1.48, 95% CI 1.00-1.96, P=.049). Conclusions: In pituitary adenoma patients, an increased incidence of stroke was observed compared with the general population. However, postoperative RT was not associated with an increased incidence of stroke or differences in causative mechanism or anatomic localization of stroke compared with surgery alone. The primary stroke risk

Incidence, Causative Mechanisms, and Anatomic Localization of Stroke in Pituitary Adenoma Patients Treated With Postoperative Radiation Therapy Versus Surgery Alone

International Nuclear Information System (INIS)

Sattler, Margriet G.A.; Vroomen, Patrick C.; Sluiter, Wim J.; Schers, Henk J.; Berg, Gerrit van den; Langendijk, Johannes A.; Wolffenbuttel, Bruce H.R.; Bergh, Alphons C.M. van den; Beek, André P. van

2013-01-01

Purpose: To assess and compare the incidence of stroke and stroke subtype in pituitary adenoma patients treated with postoperative radiation therapy (RT) and surgery alone. Methods and Materials: A cohort of 462 pituitary adenoma patients treated between 1959 and 2008 at the University Medical Center Groningen in The Netherlands was studied. Radiation therapy was administered in 236 patients. The TOAST (Trial of ORG 10172 in Acute Stroke Treatment) and the Oxfordshire Community Stroke Project classification methods were used to determine causative mechanism and anatomic localization of stroke. Stroke incidences in patients treated with RT were compared with that observed after surgery alone. Risk factors for stroke incidence were studied by log–rank test, without and with stratification for other significant risk factors. In addition, the stroke incidence was compared with the incidence rate in the general Dutch population. Results: Thirteen RT patients were diagnosed with stroke, compared with 12 surgery-alone patients. The relative risk (RR) for stroke in patients treated with postoperative RT was not significantly different compared with surgery-alone patients (univariate RR 0.62, 95% confidence interval [CI] 0.28-1.35, P=.23). Stroke risk factors were coronary or peripheral artery disease (univariate and multivariate RR 10.4, 95% CI 4.7-22.8, P<.001) and hypertension (univariate RR 3.9, 95% CI 1.6-9.8, P=.002). There was no difference in TOAST and Oxfordshire classification of stroke. In this pituitary adenoma cohort 25 strokes were observed, compared with 16.91 expected (standard incidence ratio 1.48, 95% CI 1.00-1.96, P=.049). Conclusions: In pituitary adenoma patients, an increased incidence of stroke was observed compared with the general population. However, postoperative RT was not associated with an increased incidence of stroke or differences in causative mechanism or anatomic localization of stroke compared with surgery alone. The primary stroke risk

Tumor bulk as a prognostic factor for the management of localized aggressive non-Hodgkin's lymphoma: a survey of the Japan lymphoma radiation therapy group

International Nuclear Information System (INIS)

Oguchi, Masahiko; Ikeda, Hiroshi; Isobe, Kouichi; Hirota, Saeko; Hasegawa, Masatoshi; Nakamura, Katsumasa; Sasai, Keisuke; Hayabuchi, Naofumi

2000-01-01

Purpose: To identify the prognostic factors that specifically predict survival rates of patients with localized aggressive non-Hodgkin's lymphoma (NHL). Methods and Materials: The survey was carried out at 25 radiation oncology institutions in Japan in 1998. The 5-year event-free (EFS) and overall survival rates (OAS) were calculated, and univariate and multivariate analyses were done to identify which of the following factors, namely, gender, age, performance status (PS), serum lactate dehydrogenase (LDH) level, Stage (I vs. II), tumor bulk (maximum diameter), and treatment, were significant from the viewpoint of prognosis. Results: A total of 1141 patients with Stage I and II NHL were treated by the Japanese Lymphoma Radiation Therapy Group between 1988 and 1992. Of them, 787 patients, who were treated using definitive radiotherapy with or without chemotherapy for intermediate- and high-grade lymphomas in working formulation, constituted the core of this study. Primary tumors arose mainly from extranodal organs (71%) in the head and neck (Waldeyer's ring: 36% and sinonasal cavities: 9%). The factors associated with poorer prognosis were age over 60 years old (p < 0.0001), radiation therapy alone (p < 0.0001), PS = 2-4 (p = 0.0011), (sex male, p = 0.0078), a bulky tumor more than 6 cm in maximum diameter (p 0.0088), elevated LDH (p = 0.0117), and stage II (p = 0.0642). A median dose of 42 Gy was delivered mainly to the involved fields. Short-course chemotherapy was provided in 549 (70%) patients. The 5-year OAS and EFS rates for all patients were 71% and 67%, respectively. According to the stage-modified International Prognostic Index, the 5-year EFS of the patients with risk factors from 0 to 1 was 76%, 61% for patients with two risk factors, and 26% for patients with three or more risk factors. Conclusion: Extranodal presentation, especially Waldeyer's ring and sinonasal cavities, is encountered more frequently in Japan than in Western countries. Tumor bulk is

The fungal resistome: a risk and an opportunity for the development of novel antifungal therapies.

Science.gov (United States)

Reales-Calderón, Jose A; Molero, Gloria; Gil, Concha; Martínez, José L

2016-08-01

The risks for toxicity of novel antifungal compounds, together with the emergence of resistance, makes the use of inhibitors of resistance, in combination with antifungal compounds, a suitable strategy for developing novel antifungal formulations. Among them, inhibitors of efflux pumps are suitable candidates. Increasing drug influx or interfering with the stress response may also improve the efficacy of antifungals. Therapies as induction of fungal apoptosis or immunostimulation are also good strategies for reducing the risks for resistance and to improve antifungals' efficacy. Understanding the effect of the acquisition of resistance on the fungal physiology and determining the collateral sensitivity networks are useful for the development of novel strategies based on combination of antifungals for improving the efficacy of the therapy.

Novel strategies in glioblastoma surgery aim at safe, supra-maximum resection in conjunction with local therapies.

Science.gov (United States)

Wolbers, John G

2014-01-01

The biggest challenge in neuro-oncology is the treatment of glioblastoma, which exhibits poor prognosis and is increasing in incidence in an increasing aging population. Diverse treatment strategies aim at maximum cytoreduction and ensuring good quality of life. We discuss multimodal neuronavigation, supra-maximum tumor resection, and the postoperative treatment gap. Multimodal neuronavigation allows the integration of preoperative anatomic and functional data with intraoperative information. This approach includes functional magnetic resonance imaging (MRI) and diffusion tensor imaging in preplanning and ultrasound, computed tomography (CT), MRI and direct (sub)cortical stimulation during surgery. The practice of awake craniotomy decreases postoperative neurologic deficits, and an extensive supra-maximum resection appears to be feasible, even in eloquent areas of the brain. Intraoperative MRI- and fluorescence-guided surgery assist in achieving this goal of supra-maximum resection and have been the subject of an increasing number of reports. Photodynamic therapy and local chemotherapy are properly positioned to bridge the gap between surgery and chemoradiotherapy. The photosensitizer used in fluorescence-guided surgery persists in the remaining peripheral tumor extensions. Additionally, blinded randomized clinical trials showed firm evidence of extra cytoreduction by local chemotherapy in the tumor cavity. The cutting-edge promise is gene therapy although both the delivery and efficacy of the numerous transgenes remain under investigation. Issues such as the choice of (cell) vector, the choice of therapeutic transgene, the optimal route of administration, and biosafety need to be addressed in a systematic way. In this selective review, we present various evidence and promises to improve survival of glioblastoma patients by supra-maximum cytoreduction via local procedures while minimizing the risk of new neurologic deficit.

Antiretroviral therapy during pregnancy and the risk of an adverse outcome.

Science.gov (United States)

Tuomala, Ruth E; Shapiro, David E; Mofenson, Lynne M; Bryson, Yvonne; Culnane, Mary; Hughes, Michael D; O'Sullivan, M J; Scott, Gwendolyn; Stek, Alice M; Wara, Diane; Bulterys, Marc

2002-06-13

Some studies suggest that combination antiretroviral therapy in pregnant women with human immunodeficiency virus type 1 (HIV-1) infection increases the risk of premature birth and other adverse outcomes of pregnancy. We studied pregnant women with HIV-1 infection who were enrolled in seven clinical studies and delivered their infants from 1990 through 1998. The cohort comprised 2123 women who received antiretroviral therapy during pregnancy (monotherapy in 1590, combination therapy without protease inhibitors in 396, and combination therapy with protease inhibitors in 137) and 1143 women who did not receive antiretroviral therapy. After standardization for the CD4+ cell count and use or nonuse of tobacco, alcohol, and illicit drugs, the rate of premature delivery (women who received antiretroviral therapy and those who did not (16 percent and 17 percent, respectively); the rate of low birth weight (women who received combination therapy with protease inhibitors (5 percent) had infants with very low birth weight, as compared with nine women who received combination therapy without protease inhibitors (2 percent) (adjusted odds ratio, 3.56; 95 percent confidence interval, 1.04 to 12.19). As compared with no antiretroviral therapy or monotherapy, combination therapy for HIV-1 infection in pregnant women is not associated with increased rates of premature delivery or with low birth weight, low Apgar scores, or stillbirth in their infants. The association between combination therapy with protease inhibitors and an increased risk of very low birth weight requires confirmation.

Quit Now! A Psychoeducational Expressive Therapy Group Work Approach for At-Risk and Delinquent Adolescent Smokers in Singapore

Science.gov (United States)

Kit, Phey Ling; Teo, Lan

2012-01-01

In this article, we review the risk and protective factors for adolescent smoking, as well as current research on evidence-based practices. The relevance of structured expressive therapy in meeting the maturational and emotional needs of at-risk and delinquent adolescents, and the multicultural context of adolescents in Singapore's Asian society…

Lifetime risk of renal replacement therapy in Europe: a population-based study using data from the ERA-EDTA Registry.

Science.gov (United States)

van den Brand, Jan A J G; Pippias, Maria; Stel, Vianda S; Caskey, Fergus J; Collart, Frederic; Finne, Partik; Heaf, James; Jais, Jean-Philippe; Kramar, Reinhard; Massy, Ziad A; De Meester, Johan; Traynor, Jamie P; Reisæter, Anna Varberg; Wetzels, Jack F M; Jager, Kitty J

2017-02-01

Upcoming KDIGO guidelines for the evaluation of living kidney donors are expected to move towards a personal risk-based evaluation of potential donors. We present the age and sex-specific lifetime risk of renal replacement therapy (RRT) for end-stage renal disease in 10 European countries. We defined lifetime risk of RRT as the cumulative incidence of RRT up to age 90 years. We obtained RRT incidence rates per million population by 5-year age groups and sex using data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry, and used these to estimate the cumulative incidence of RRT, adjusting for competing mortality risk. Lifetime risk of RRT varied from 0.44% to 2.05% at age 20 years and from 0.17% to 1.59% at age 70 years across countries, and was twice as high in men as in women. Lifetime RRT risk decreased with age, ranging from an average of 0.77% to 0.44% in 20- to- 70-year-old women, and from 1.45% to 0.96% in 20- to- 70-year-old men. The lifetime risk of RRT increased slightly over the past decade, more so in men than in women. However, it appears to have stabilized or even decreased slightly in more recent years. The lifetime risk of RRT decreased with age, was lower in women as compared with men of equal age and varied considerably throughout Europe. Given the substantial differences in lifetime risk of RRT between the USA and Europe, country-specific estimates should be used in the evaluation and communication of the risk of RRT for potential living kidney donors. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

A Monte Carlo-based treatment-planning tool for ion beam therapy

CERN Document Server

Böhlen, T T; Dosanjh, M; Ferrari, A; Haberer, T; Parodi, K; Patera, V; Mairan, A

2013-01-01

Ion beam therapy, as an emerging radiation therapy modality, requires continuous efforts to develop and improve tools for patient treatment planning (TP) and research applications. Dose and fluence computation algorithms using the Monte Carlo (MC) technique have served for decades as reference tools for accurate dose computations for radiotherapy. In this work, a novel MC-based treatment-planning (MCTP) tool for ion beam therapy using the pencil beam scanning technique is presented. It allows single-field and simultaneous multiple-fields optimization for realistic patient treatment conditions and for dosimetric quality assurance for irradiation conditions at state-of-the-art ion beam therapy facilities. It employs iterative procedures that allow for the optimization of absorbed dose and relative biological effectiveness (RBE)-weighted dose using radiobiological input tables generated by external RBE models. Using a re-implementation of the local effect model (LEM), theMCTP tool is able to perform TP studies u...

Mindfulness-based cognitive therapy for depression: trends and developments

OpenAIRE

MacKenzie, Meagan B; Kocovski, Nancy L

2016-01-01

Meagan B MacKenzie,1 Nancy L Kocovski21Department of Psychology, Ryerson University, Toronto, ON, Canada; 2Department of Psychology, Wilfrid Laurier University, Waterloo, ON, CanadaAbstract: Mindfulness-based cognitive therapy (MBCT) was developed as a psychological intervention for individuals at risk of depressive relapse. Possible mechanisms of change for this intervention are in line with its theoretical underpinnings, and include increases in mindfulness and/or decreases in nega...

Monthly rifampicin, ofloxacin, and minocycline therapy for generalized and localized granuloma annulare

Directory of Open Access Journals (Sweden)

Shilpa Garg

2015-01-01

Full Text Available Background: The localized form of granuloma annulare is usually self-limiting, resolving within 2 years. Generalized granuloma annulare, on the other hand, runs a protracted course, with spontaneous resolution being rare. It is also characterized by a later age of onset, an increased incidence of diabetes mellitus, poor response to therapy, and an increased prevalence of HLA Bw35. Objective: To assess the efficacy of monthly pulsed rifampicin, ofloxacin, and minocycline (ROM therapy in the management of granuloma annulare. Methods : Six biopsy proven patients of granuloma annulare were included in the study, five of the generalized variety, and one localized. Three of these patients were resistant to standard modalities of treatment. All six patients were treated with pulses of once monthly ROM till complete resolution of all lesions. Results were analyzed in terms of complete resolution of lesions and side effects. Presence of comorbid conditions was noted. Result: All six patients were successfully treated with 4-8 pulses of monthly ROM. None of the patients reported any adverse effects. Limitations: Small sample size and the lack of a control group are limitations. Conclusion: Treatment with pulses of once monthly ROM caused complete resolution of lesions in both localized and generalized granuloma annulare, even in cases recalcitrant to conventional therapy. There were no side effects in any of the patients. Larger trials are needed to substantiate the efficacy of monthly ROM in granuloma annulare.

Prognostic Value of External Beam Radiation Therapy in Patients Treated With Surgical Resection and Intraoperative Electron Beam Radiation Therapy for Locally Recurrent Soft Tissue Sarcoma: A Multicentric Long-Term Outcome Analysis

Energy Technology Data Exchange (ETDEWEB)

Calvo, Felipe A. [Department of Oncology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); School of Medicine, Complutense University, Madrid (Spain); Sole, Claudio V., E-mail: cvsole@uc.cl [Department of Oncology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); School of Medicine, Complutense University, Madrid (Spain); Service of Radiation Oncology, Instituto de Radiomedicina, Santiago (Chile); Cambeiro, Mauricio [Service of Radiation Oncology, Clínica Universitaria, Universidad de Navarra, Pamplona (Spain); Montero, Angel; Polo, Alfredo [Service of Radiation Oncology, Hospital Universitario Ramón y Cajal, Universidad de Alcala, Madrid (Spain); Gonzalez, Carmen [School of Medicine, Complutense University, Madrid (Spain); Service of Radiation Oncology, Instituto de Radiomedicina, Santiago (Chile); Service of Radiation Oncology, Clínica Universitaria, Universidad de Navarra, Pamplona (Spain); Service of Radiation Oncology, Hospital Universitario Ramón y Cajal, Universidad de Alcala, Madrid (Spain); Service of Radiation Oncology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); Cuervo, Miguel [Service of Orthopedics and Traumatology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); San Julian, Mikel [Service of Orthopedics and Traumatology, Clínica Universitaria, Universidad de Navarra, Pamplona (Spain); and others

2014-01-01

Background: A joint analysis of data from centers involved in the Spanish Cooperative Initiative for Intraoperative Electron Radiotherapy was performed to investigate long-term outcomes of locally recurrent soft tissue sarcoma (LR-STS) patients treated with a multidisciplinary approach. Methods and Materials: Patients with a histologic diagnosis of LR-STS (extremity, 43%; trunk wall, 24%; retroperitoneum, 33%) and no distant metastases who underwent radical surgery and intraoperative electron radiation therapy (IOERT; median dose, 12.5 Gy) were considered eligible for participation in this study. In addition, 62% received external beam radiation therapy (EBRT; median dose, 50 Gy). Results: From 1986 to 2012, a total of 103 patients from 3 Spanish expert IOERT institutions were analyzed. With a median follow-up of 57 months (range, 2-311 months), 5-year local control (LC) was 60%. The 5-year IORT in-field control, disease-free survival (DFS), and overall survival were 73%, 43%, and 52%, respectively. In the multivariate analysis, no EBRT to treat the LR-STS (P=.02) and microscopically involved margin resection status (P=.04) retained significance in relation to LC. With regard to IORT in-field control, only not delivering EBRT to the LR-STS retained significance in the multivariate analysis (P=.03). Conclusion: This joint analysis revealed that surgical margin and EBRT affect LC but that, given the high risk of distant metastases, DFS remains modest. Intensified local treatment needs to be further tested in the context of more efficient concurrent, neoadjuvant, and adjuvant systemic therapy.

Prognostic Value of External Beam Radiation Therapy in Patients Treated With Surgical Resection and Intraoperative Electron Beam Radiation Therapy for Locally Recurrent Soft Tissue Sarcoma: A Multicentric Long-Term Outcome Analysis

International Nuclear Information System (INIS)

Calvo, Felipe A.; Sole, Claudio V.; Cambeiro, Mauricio; Montero, Angel; Polo, Alfredo; Gonzalez, Carmen; Cuervo, Miguel; San Julian, Mikel

2014-01-01

Background: A joint analysis of data from centers involved in the Spanish Cooperative Initiative for Intraoperative Electron Radiotherapy was performed to investigate long-term outcomes of locally recurrent soft tissue sarcoma (LR-STS) patients treated with a multidisciplinary approach. Methods and Materials: Patients with a histologic diagnosis of LR-STS (extremity, 43%; trunk wall, 24%; retroperitoneum, 33%) and no distant metastases who underwent radical surgery and intraoperative electron radiation therapy (IOERT; median dose, 12.5 Gy) were considered eligible for participation in this study. In addition, 62% received external beam radiation therapy (EBRT; median dose, 50 Gy). Results: From 1986 to 2012, a total of 103 patients from 3 Spanish expert IOERT institutions were analyzed. With a median follow-up of 57 months (range, 2-311 months), 5-year local control (LC) was 60%. The 5-year IORT in-field control, disease-free survival (DFS), and overall survival were 73%, 43%, and 52%, respectively. In the multivariate analysis, no EBRT to treat the LR-STS (P=.02) and microscopically involved margin resection status (P=.04) retained significance in relation to LC. With regard to IORT in-field control, only not delivering EBRT to the LR-STS retained significance in the multivariate analysis (P=.03). Conclusion: This joint analysis revealed that surgical margin and EBRT affect LC but that, given the high risk of distant metastases, DFS remains modest. Intensified local treatment needs to be further tested in the context of more efficient concurrent, neoadjuvant, and adjuvant systemic therapy

Morbidity and mortality of local failure after definitive therapy for prostate cancer

International Nuclear Information System (INIS)

Schellhammer, P.F.; Whitmore, R.B. III; Kuban, D.A.; el-Mahdi, A.M.; Ladaga, L.A.

1989-01-01

We reviewed our experience with morbidity and mortality associated with clinical local failure after definitive therapy for adenocarcinoma of the prostate by interstitial 125-iodine implantation, external beam radiation therapy or radical prostatectomy. Morbid complications included unilateral ureteral obstruction; bladder obstruction and/or incontinence requiring treatment by transurethral resection, or placement of a urethral or suprapubic catheter; hematuria requiring intervention for clot evacuation or fulguration, and perineal and/or pelvic pain. Lethal complications included bilateral ureteral obstruction or bowel obstruction. We treated 108 patients with 125-iodine, 178 with external beam radiotherapy and 67 with radical prostatectomy. Clinical local failure occurred in 26 per cent of the 125-iodine, 17 per cent of the external beam radiotherapy and 12 per cent of the radical prostatectomy groups. The total incidence of local failure with 125-iodine was statistically higher than for radical prostatectomy. Stage C and poorly differentiated tumors were associated with a statistically higher incidence of local failure compared to lower stage and grade tumors. However, within each stage and grade there was no significant difference in local failure between treatment modalities. There was negligible morbidity or mortality secondary to local failure associated with stage A2, stage B1 or well differentiated tumors regardless of treatment modality. There was no difference in the morbidity and mortality between treatment modalities for stage C or poorly differentiated tumors. However, for stage B2 or moderately differentiated tumors treated by 125-iodine implantation there was a statistically greater incidence of morbidity and mortality than that associated with external beam radiotherapy and radical prostatectomy

Modern Radiation Therapy for Hodgkin Lymphoma

DEFF Research Database (Denmark)

Specht, Lena; Yahalom, Joachim; Illidge, Tim

2014-01-01

Radiation therapy (RT) is the most effective single modality for local control of Hodgkin lymphoma (HL) and an important component of therapy for many patients. These guidelines have been developed to address the use of RT in HL in the modern era of combined modality treatment. The role of reduced...... on Radiation Units and Measurements concepts of gross tumor volume, clinical target volume, internal target volume, and planning target volume are used for defining the targeted volumes. Newer treatment techniques, including intensity modulated radiation therapy, breath-hold, image guided radiation therapy......, and 4-dimensional imaging, should be implemented when their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control. The highly conformal involved node radiation therapy (INRT), recently introduced for patients for whom...

Theory-based training strategies for modifying practitioner concerns about exposure therapy.

Science.gov (United States)

Farrell, Nicholas R; Deacon, Brett J; Dixon, Laura J; Lickel, James J

2013-12-01

Despite the well-established efficacy of exposure therapy in the treatment of pathological anxiety, many therapists believe this treatment carries an unacceptably high risk for harm, is intolerable for patients, and poses a number of ethical quandaries. These beliefs have been shown to account for two related problems: (a) underutilization of exposure therapy, and (b) overly cautious and suboptimal delivery the treatment, which likely attenuates treatment outcomes. At present, there is little guidance for those who train exposure therapists to address these concerns. This article reviews therapist negative beliefs about exposure therapy and discusses their modification based on findings from social and cognitive psychology pertinent to belief change, including dual-processing in reasoning, the need for cognition and affect, and attitude inoculation. A number of strategies are offered for augmenting training in exposure therapy in order to promote positive beliefs about the treatment. These strategies involve: (a) therapists engaging in simulated exposure therapy exercises and presenting arguments in defense of exposure's safety, tolerability, and ethicality, and (b) training therapists using emotion-based appeals (e.g., case examples) to supplement research findings. Directions for future research on practitioner concerns about exposure therapy are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Risk of breast cancer by type of menopausal hormone therapy: a case-control study among post-menopausal women in France.

Directory of Open Access Journals (Sweden)

Emilie Cordina-Duverger

Full Text Available BACKGROUND: There is extensive epidemiological evidence that menopausal hormone therapy (MHT increases breast cancer risk, particularly combinations of estrogen and progestagen (EP. We investigated the effects of the specific formulations and types of therapies used by French women. Progestagen constituents, regimen (continuous or sequential treatment by the progestagen, and time interval between onset of menopause and start of MHT were examined. METHODS: We conducted a population-based case-control study in France in 1555 menopausal women (739 cases and 816 controls. Detailed information on MHT use was obtained during in-person interviews. Odds ratios and 95% confidence interval adjusted for breast cancer risk factors were calculated. RESULTS: We found that breast cancer risk differed by type of progestagen among current users of EP therapies. No increased risk was apparent among EP therapy users treated with natural micronized progesterone. Among users of EP therapy containing a synthetic progestin, the odds ratio was 1.57 (0.99-2.49 for progesterone-derived and 3.35 (1.07-10.4 for testosterone-derived progestagen. Women with continuous regimen were at greater risk than women treated sequentially, but regimen and type of progestagen could not be investigated independently, as almost all EP combinations containing a testosterone-derivative were administered continuously and vice-versa. Tibolone was also associated with an increased risk of breast cancer. Early users of MHT after onset of menopause were at greater risk than users who delayed treatment. CONCLUSION: This study confirms differential effects on breast cancer risk of progestagens and regimens specifically used in France. Formulation of EP therapies containing natural progesterone, frequently prescribed in France, was not associated with increased risk of breast cancer but may poorly protect against endometrial cancer.

Localizing obstructive sites with dynamic MRI and consequentially proper therapy selection for obstructive sleep apnea/hypopnea syndrome

International Nuclear Information System (INIS)

Oda, Makoto

2004-01-01

At present, selection of therapies for obstructive sleep apnea/hypopnea syndrome (OSAHS) relies on the localizing the obstructive sites and determination of its severity by polysomnography (PSG). Many methods have been applied to localize the obstructive sites. We attempted to evaluate the morphology of upper airway during sleep with dynamic MRI, and assessed the severity of OSAHS and results of therapies in groups classified by the patterns of obstructive sites. A categorizing system was set up, by which the obstructive sites were reviewed on axial and sagittal sections and accordingly classified into four patterns: front-to-back pattern, left-to-right pattern, circular pattern and epiglottis pattern. Comparison of apnea/hypopnea index (AHI), lowest SpO2 and BMI was performed between the different patterns. The results showed that the left-to-right pattern and circular pattern had a higher AHI and lower lowest SpO2, and more cases of obesity with higher BMI were found in these two groups. We also evaluated the results of different therapies for different obstructive site patterns. Radiofrequency coblation of soft palate was found to be effective for the front-to-back pattern. Improvement was found in 67% of all the cases that received uvulopalatopharyngoplasty (UPPP), while a significant postoperative improvement of AHI was confirmed in left-to-right pattern and circular pattern groups. No significant difference in the results was found between different obstructive sites or patterns when nasal continuous positive airway pressure (n-CPAP) was applied alone. Being completely free from CPAP (completed treatment with improvement of symptoms) was achieved in 71.4% of all the cases and 85.7% in the left-to-right pattern group who received UPPP. We conclude that an optimal treatment results could be achieved by selecting the therapies based on the severity of OSAHS and result of localizing the obstructive sites by dynamic MRI. (author)

Trends in Local Therapy Utilization and Cost for Early-Stage Breast Cancer in Older Women: Implications for Payment and Policy Reform

International Nuclear Information System (INIS)

Shirvani, Shervin M.; Jiang, Jing; Likhacheva, Anna; Hoffman, Karen E.; Shaitelman, Simona F.; Caudle, Abigail; Buchholz, Thomas A.; Giordano, Sharon H.; Smith, Benjamin D.

2016-01-01

Purpose: Older women with early-stage disease constitute the most rapidly growing breast cancer demographic, yet it is not known which local therapy strategies are most favored by this population in the current era. Understanding utilization trends and cost of local therapy is important for informing the design of bundled payment models as payers migrate away from fee-for-service models. We therefore used the Surveillance, Epidemiology, and End Results Medicare database to determine patterns of care and costs for local therapy among older women with breast cancer. Methods and Materials: Treatment strategy and covariables were determined in 55,327 women age ≥66 with Tis-T2N0-1M0 breast cancer who underwent local therapy between 2000 and 2008. Trends in local therapy were characterized using Joinpoint. Polychotomous logistic regression determined predictors of local therapy. The median aggregate cost over the first 24 months after diagnosis was determined from Medicare claims through 2010 and reported in 2014 dollars. Results: The median age was 75. Local therapy distribution was as follows: 27,896 (50.3%) lumpectomy with external beam radiation, 18,356 (33.1%) mastectomy alone, 6159 (11.1%) lumpectomy alone, 1488 (2.7%) mastectomy with reconstruction, and 1455 (2.6%) lumpectomy with brachytherapy. Mastectomy alone declined from 39.0% in 2000 to 28.2% in 2008, and the use of breast conserving local therapies rose from 58.7% to 68.2%. Mastectomy with reconstruction was more common among the youngest, healthiest patients, whereas mastectomy alone was more common among patients living in rural low-income regions. By 2008, the costs were $36,749 for lumpectomy with brachytherapy, $35,030 for mastectomy with reconstruction, $31,388 for lumpectomy with external beam radiation, $21,993 for mastectomy alone, and $19,287 for lumpectomy alone. Conclusions: The use of mastectomy alone in older women declined in favor of breast conserving strategies between 2000 and 2008

Trends in Local Therapy Utilization and Cost for Early-Stage Breast Cancer in Older Women: Implications for Payment and Policy Reform

Energy Technology Data Exchange (ETDEWEB)

Shirvani, Shervin M. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, Banner MD Anderson Cancer Center, Gilbert, Arizona (United States); Jiang, Jing [Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Likhacheva, Anna [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, Banner MD Anderson Cancer Center, Gilbert, Arizona (United States); Hoffman, Karen E.; Shaitelman, Simona F. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Caudle, Abigail [Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Buchholz, Thomas A. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Giordano, Sharon H. [Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Smith, Benjamin D., E-mail: bsmith3@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2016-06-01

Purpose: Older women with early-stage disease constitute the most rapidly growing breast cancer demographic, yet it is not known which local therapy strategies are most favored by this population in the current era. Understanding utilization trends and cost of local therapy is important for informing the design of bundled payment models as payers migrate away from fee-for-service models. We therefore used the Surveillance, Epidemiology, and End Results Medicare database to determine patterns of care and costs for local therapy among older women with breast cancer. Methods and Materials: Treatment strategy and covariables were determined in 55,327 women age ≥66 with Tis-T2N0-1M0 breast cancer who underwent local therapy between 2000 and 2008. Trends in local therapy were characterized using Joinpoint. Polychotomous logistic regression determined predictors of local therapy. The median aggregate cost over the first 24 months after diagnosis was determined from Medicare claims through 2010 and reported in 2014 dollars. Results: The median age was 75. Local therapy distribution was as follows: 27,896 (50.3%) lumpectomy with external beam radiation, 18,356 (33.1%) mastectomy alone, 6159 (11.1%) lumpectomy alone, 1488 (2.7%) mastectomy with reconstruction, and 1455 (2.6%) lumpectomy with brachytherapy. Mastectomy alone declined from 39.0% in 2000 to 28.2% in 2008, and the use of breast conserving local therapies rose from 58.7% to 68.2%. Mastectomy with reconstruction was more common among the youngest, healthiest patients, whereas mastectomy alone was more common among patients living in rural low-income regions. By 2008, the costs were $36,749 for lumpectomy with brachytherapy, $35,030 for mastectomy with reconstruction, $31,388 for lumpectomy with external beam radiation, $21,993 for mastectomy alone, and $19,287 for lumpectomy alone. Conclusions: The use of mastectomy alone in older women declined in favor of breast conserving strategies between 2000 and 2008

A model-based risk management framework

Energy Technology Data Exchange (ETDEWEB)

Gran, Bjoern Axel; Fredriksen, Rune

2002-08-15

The ongoing research activity addresses these issues through two co-operative activities. The first is the IST funded research project CORAS, where Institutt for energiteknikk takes part as responsible for the work package for Risk Analysis. The main objective of the CORAS project is to develop a framework to support risk assessment of security critical systems. The second, called the Halden Open Dependability Demonstrator (HODD), is established in cooperation between Oestfold University College, local companies and HRP. The objective of HODD is to provide an open-source test bed for testing, teaching and learning about risk analysis methods, risk analysis tools, and fault tolerance techniques. The Inverted Pendulum Control System (IPCON), which main task is to keep a pendulum balanced and controlled, is the first system that has been established. In order to make risk assessment one need to know what a system does, or is intended to do. Furthermore, the risk assessment requires correct descriptions of the system, its context and all relevant features. A basic assumption is that a precise model of this knowledge, based on formal or semi-formal descriptions, such as UML, will facilitate a systematic risk assessment. It is also necessary to have a framework to integrate the different risk assessment methods. The experiences so far support this hypothesis. This report presents CORAS and the CORAS model-based risk management framework, including a preliminary guideline for model-based risk assessment. The CORAS framework for model-based risk analysis offers a structured and systematic approach to identify and assess security issues of ICT systems. From the initial assessment of IPCON, we also believe that the framework is applicable in a safety context. Further work on IPCON, as well as the experiences from the CORAS trials, will provide insight and feedback for further improvements. (Author)

Radiotherapy-induced secondary cancer risk for breast cancer: 3D conformal therapy versus IMRT versus VMAT

International Nuclear Information System (INIS)

Lee, Boram; Sung, Jiwon; Yoon, Myonggeun; Lee, Sunyoung

2014-01-01

This study evaluated the secondary cancer risk to various organs due to radiation treatment for breast cancer. Organ doses to an anthropomorphic phantom were measured using a photoluminescent dosimeter (PLD) for breast cancer treatment with 3D conformal radiation therapy (3D-CRT), intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). Cancer risk based on the measured dose was calculated using the BEIR (Biological Effects of Ionizing Radiation) VII models. The secondary dose per treatment dose (50.4 Gy) to various organs ranged from 0.02 to 0.36 Gy for 3D-CRT, but from 0.07 to 8.48 Gy for IMRT and VMAT, indicating that the latter methods are associated with higher secondary radiation doses than 3D-CRT. The result of the homogeneity index in the breast target shows that the dose homogeneity of 3D-CRT was worse than those of IMRT and VMAT. The organ specific lifetime attributable risks (LARs) to the thyroid, contralateral breast and ipsilateral lung per 100 000 population were 0.02, 19.71, and 0.76 respectively for 3D-CRT, much lower than the 0.11, 463.56, and 10.59 respectively for IMRT and the 0.12, 290.32, and 12.28 respectively for VMAT. The overall estimation of LAR indicated that the radiation-induced cancer risk due to breast radiation therapy was lower with 3D-CRT than with IMRT or VMAT. (paper)

Recent Change of locality as Risk factor for Malaria Fever Among ...

African Journals Online (AJOL)

Recent Change of locality as Risk factor for Malaria Fever Among New Residents of Ahoada East Local Government Area in Southern Nigeria. ... an endemic region, which serves as an indicator of exposure to new variants of P falciparum; for which specific immunity is lacking, is a significant risk factor for malaria fever.

Baseline characteristics predict risk of progression and response to combined medical therapy for benign prostatic hyperplasia (BPH).

Science.gov (United States)

Kozminski, Michael A; Wei, John T; Nelson, Jason; Kent, David M

2015-02-01

To better risk stratify patients, using baseline characteristics, to help optimise decision-making for men with moderate-to-severe lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) through a secondary analysis of the Medical Therapy of Prostatic Symptoms (MTOPS) trial. After review of the literature, we identified potential baseline risk factors for BPH progression. Using bivariate tests in a secondary analysis of MTOPS data, we determined which variables retained prognostic significance. We then used these factors in Cox proportional hazard modelling to: i) more comprehensively risk stratify the study population based on pre-treatment parameters and ii) to determine which risk strata stood to benefit most from medical intervention. In all, 3047 men were followed in MTOPS for a mean of 4.5 years. We found varying risks of progression across quartiles. Baseline BPH Impact Index score, post-void residual urine volume, serum prostate-specific antigen (PSA) level, age, American Urological Association Symptom Index score, and maximum urinary flow rate were found to significantly correlate with overall BPH progression in multivariable analysis. Using baseline factors permits estimation of individual patient risk for clinical progression and the benefits of medical therapy. A novel clinical decision tool based on these analyses will allow clinicians to weigh patient-specific benefits against possible risks of adverse effects for a given patient. © 2014 The Authors. BJU International © 2014 BJU International.

The Effect of Radiation Timing on Patients With High-Risk Features of Parameningeal Rhabdomyosarcoma: An Analysis of IRS-IV and D9803

Energy Technology Data Exchange (ETDEWEB)

Spalding, Aaron C., E-mail: Aaron.Spalding@nortonhealthcare.org [Kosair Children' s Hospital and Brain Tumor Center, Louisville, Kentucky (United States); Hawkins, Douglas S. [Division of Hematology/Oncology, Seattle Children' s Hospital, and Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington (United States); Donaldson, Sarah S. [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Anderson, James R.; Lyden, Elizabeth [University of Nebraska Medical Center, Omaha, Nebraska (United States); Laurie, Fran [Quality Assurance Review Center, Providence, Rhode Island and Seattle, Washington (United States); Wolden, Suzanne L. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Arndt, Carola A.S. [Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota (United States); Michalski, Jeff M. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

2013-11-01

Purpose: Radiation therapy remains an essential treatment for patients with parameningeal rhabdomyosarcoma (PMRMS), and early radiation therapy may improve local control for patients with intracranial extension (ICE). Methods and Materials: To address the role of radiation therapy timing in PMRMS in the current era, we reviewed the outcome from 2 recent clinical trials for intermediate-risk RMS: Intergroup Rhabdomyosarcoma Study (IRS)-IV and Children's Oncology Group (COG) D9803. The PMRMS patients on IRS-IV with any high-risk features (cranial nerve palsy [CNP], cranial base bony erosion [CBBE], or ICE) were treated immediately at day 0, and PMRMS patients without any of these 3 features received week 6-9 radiation therapy. The D9803 PMRMS patients with ICE received day 0 X-Ray Therapy (XRT) as well; however, those with either CNP or CBBE had XRT at week 12. Results: Compared with the 198 PMRMS patients from IRS-IV, the 192 PMRMS patients from D9803 had no difference (P<.05) in 5-year local failure (19% vs 19%), failure-free-survival (70% vs 67%), or overall survival (75% vs 73%) in aggregate. The 5-year local failure rates by subset did not differ when patients were classified as having no risk features (None, 15% vs 19%, P=.25), cranial nerve palsy/cranial base of skull erosion (CNP/CBBE, 15% vs 28%, P=.22), or intracranial extension (ICE, 21% vs 15%, P=.27). The D9083 patients were more likely to have received initial staging by magnetic resonance imaging (71% vs 53%). Conclusions: These data support that a delay in radiation therapy for high-risk PMRMS features of CNP/CBBE does not compromise clinical outcomes.

Local transdermal therapy to the breast for breast cancer prevention and DCIS therapy: preclinical and clinical evaluation.

Science.gov (United States)

Lee, Oukseub; Ivancic, David; Allu, Subhashini; Shidfar, Ali; Kenney, Kara; Helenowski, Irene; Sullivan, Megan E; Muzzio, Miguel; Scholtens, Denise; Chatterton, Robert T; Bethke, Kevin P; Hansen, Nora M; Khan, Seema A

2015-12-01

Women at high risk of breast cancer and those with carcinoma in situ need non-toxic, well-tolerated preventive interventions. One promising approach is drug delivery through the breast skin (local transdermal therapy, LTT). Our goal was to test novel drugs for LTT, to establish that LTT is applicable to non-steroidal drugs. Athymic nude rats were treated with oral tamoxifen, transdermal 4-hydroxytamoxifen (4-OHT) or endoxifen gel applied daily to the axillary mammary gland for 6 weeks (Study 1). Study 2 was identical to Study 1, testing transdermal telapristone acetate (telapristone) gel versus subcutaneous implant. At euthanasia, mammary glands and blood were collected. In Study 3, consenting women requiring mastectomy were randomized to diclofenac patch applied to the abdomen or the breast for 3 days preoperatively. At surgery, eight tissue samples per breast were collected from predetermined locations, along with venous blood. Drug concentrations were measured using liquid chromatography-tandem mass spectroscopy. Mammary tissue concentrations of 4-OHT, endoxifen, and telapristone were significantly higher in the axillary glands of the gel-treated animals, compared to inguinal glands or to systemically treated animals. Plasma concentrations were similar in gel and systemically treated animals. The clinical trial showed significantly higher mammary concentrations when diclofenac was applied to the breast skin versus the abdominal skin, but concentrations were variable. These results demonstrate that lipophilic drugs can be developed for LTT; although the nude rat is suitable for testing drug permeability, delivery is systemic. In human, however, transdermal application to the breast skin provides local delivery.

EFFICACY OF FIXED COMBINATION OF VALSARTAN, AMLODIPINE AND HYDROCHLOROTHIAZIDE IN COMPLEX THERAPY OF THE PATIENT OF VERY HIGH CARDIOVASCULAR RISK

Directory of Open Access Journals (Sweden)

I. M. Sokolov

2012-01-01

Full Text Available The high prevalence of arterial hypertension in association with high and very high cardiovascular risk requires widespread use of combined therapy. Current approaches to selection of combination components of antihypertensive drugs are based the efficacy of these drugs proven in multicenter randomized clinical trials. The triple combination of calcium antagonist, angiotensin II receptor blocker and thiazide diuretic is regarded as the best option for combined therapy in patients with arterial hypertension and ischemic heart disease to reduce cardiovascular risk.

Just-in-Time Training for High-Risk Low-Volume Therapies: An Approach to Ensure Patient Safety.

Science.gov (United States)

Helman, Stephanie; Lisanti, Amy Jo; Adams, Ann; Field, Cynthia; Davis, Katherine Finn

2016-01-01

High-risk low-volume therapies are those therapies that are practiced infrequently and yet carry an increased risk to patients because of their complexity. Staff nurses are required to competently manage these therapies to treat patients' unique needs and optimize outcomes; however, maintaining competence is challenging. This article describes implementation of Just-in-Time Training, which requires validation of minimum competency of bedside nurses managing high-risk low-volume therapies through direct observation of a return-demonstration competency checklist.

Arrhythmogenic Right Ventricular Cardiomyopathy: Risk Stratification and Indications for Defibrillator Therapy.

Science.gov (United States)

Zorzi, Alessandro; Rigato, Ilaria; Bauce, Barbara; Pilichou, Kalliopi; Basso, Cristina; Thiene, Gaetano; Iliceto, Sabino; Corrado, Domenico

2016-06-01

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined disease which predisposes to life-threatening ventricular arrhythmias. The main goal of ARVC therapy is prevention of sudden cardiac death (SCD). Implantable cardioverter defibrillator (ICD) is the most effective therapy for interruption of potentially lethal ventricular tachyarrhythmias. Despite its life-saving potential, ICD implantation is associated with a high rate of complications and significant impact on quality of life. Accurate risk stratification is needed to identify individuals who most benefit from the therapy. While there is general agreement that patients with a history of cardiac arrest or hemodynamically unstable ventricular tachycardia are at high risk of SCD and needs an ICD, indications for primary prevention remain a matter of debate. The article reviews the available scientific evidence and guidelines that may help to stratify the arrhythmic risk of ARVC patients and guide ICD implantation. Other therapeutic strategies, either alternative or additional to ICD, will be also addressed.

Local Control and Toxicity in a Large Cohort of Central Lung Tumors Treated With Stereotactic Body Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Modh, Ankit; Rimner, Andreas [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Williams, Eric [Department of Medical Physics Memorial Sloan Kettering Cancer Center, New York, New York (United States); Foster, Amanda; Shah, Mihir [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Shi, Weiji; Zhang, Zhigang [Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Gelblum, Daphna Y. [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Rosenzweig, Kenneth E. [Department of Radiation Oncology, Mount Sinai Medical Center, New York, New York (United States); Yorke, Ellen D.; Jackson, Andrew [Department of Medical Physics Memorial Sloan Kettering Cancer Center, New York, New York (United States); Wu, Abraham J., E-mail: wua@mskcc.org [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States)

2014-12-01

Purpose: Stereotactic body radiation therapy (SBRT) in central lung tumors has been associated with higher rates of severe toxicity. We sought to evaluate toxicity and local control in a large cohort and to identify predictive dosimetric parameters. Methods and Materials: We identified patients who received SBRT for central tumors according to either of 2 definitions. Local failure (LF) was estimated using a competing risks model, and multivariate analysis (MVA) was used to assess factors associated with LF. We reviewed patient toxicity and applied Cox proportional hazard analysis and log-rank tests to assess whether dose-volume metrics of normal structures correlated with pulmonary toxicity. Results: One hundred twenty-five patients received SBRT for non-small cell lung cancer (n=103) or metastatic lesions (n=22), using intensity modulated radiation therapy. The most common dose was 45 Gy in 5 fractions. Median follow-up was 17.4 months. Incidence of toxicity ≥ grade 3 was 8.0%, including 5.6% pulmonary toxicity. Sixteen patients (12.8%) experienced esophageal toxicity ≥ grade 2, including 50% of patients in whom PTV overlapped the esophagus. There were 2 treatment-related deaths. Among patients receiving biologically effective dose (BED) ≥80 Gy (n=108), 2-year LF was 21%. On MVA, gross tumor volume (GTV) was significantly associated with LF. None of the studied dose-volume metrics of the lungs, heart, proximal bronchial tree (PBT), or 2 cm expansion of the PBT (“no-fly-zone” [NFZ]) correlated with pulmonary toxicity ≥grade 2. There were no differences in pulmonary toxicity between central tumors located inside the NFZ and those outside the NFZ but with planning target volume (PTV) intersecting the mediastinum. Conclusions: Using moderate doses, SBRT for central lung tumors achieves acceptable local control with low rates of severe toxicity. Dosimetric analysis showed no significant correlation between dose to the lungs, heart, or NFZ and

Chemotherapy and molecular target therapy combined with radiation therapy

International Nuclear Information System (INIS)

Akimoto, Tetsuo

2012-01-01

Combined chemotherapy and radiation therapy has been established as standard treatment approach for locally advanced head and neck cancer, esophageal cancer and so on through randomized clinical trials. However, radiation-related morbidity such as acute toxicity also increased as treatment intensity has increased. In underlining mechanism for enhancement of normal tissue reaction in chemo-radiation therapy, chemotherapy enhanced radiosensitivity of normal tissues in addition to cancer cells. Molecular target-based drugs combined with radiation therapy have been expected as promising approach that makes it possible to achieve cancer-specific enhancement of radiosensitivity, and clinical trials using combined modalities have been performed to evaluate the feasibility and efficacy of this approach. In order to obtain maximum radiotherapeutic gain, a detailed understanding of the mechanism underlying the interaction between radiation and Molecular target-based drugs is indispensable. Among molecular target-based drugs, inhibitors targeting epidermal growth factor receptor (EGFR) and its signal transduction pathways have been vigorously investigated, and mechanisms regarding the radiosensitizing effect have been getting clear. In addition, the results of randomized clinical trials demonstrated that radiation therapy combined with cetuximab resulted in improvement of overall and disease-specific survival rate compared with radiation therapy in locally advanced head and neck cancer. In this review, clinical usefulness of chemo-radiation therapy and potential molecular targets for potentiation of radiation-induced cell killing are summarized. (author)

Salvage radiation therapy for locally recurrent nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Leung, To-Wai; Tung, Stewart Y.; Sze, Wing-Kin; Sze, Wai-Man; Wong, Victy Y.W.; Wong, Chi-Sing; O, Sai-Ki

2000-01-01

Purpose: To study the treatment outcome in patients with locally recurrent nasopharyngeal carcinoma (NPC) and to explore whether a combination of high-dose-rate (HDR) intracavitary brachytherapy and external beam radiation therapy (ERT) could improve the therapeutic ratio. Methods and Materials: Ninety-one patients with nonmetastatic locally recurrent NPC who were treated with curative intent during the years 1990-1999 were retrospectively analyzed. Eighty-two patients had histologically proven carcinoma. The remaining 9 had clinical and imaging features suggestive of local recurrence. The Ho's T-stage distribution at recurrence (rT) was as follows: rT1-37, rT2-14, rT3-40. Total equivalent dose (TED) was calculated by the linear-quadratic formula without a time factor correction. For those treated by combined-modality treatment (CMT), the TED was taken as the summation of the equivalent dose by ERT and the absolute dose delivered to floor of the sphenoid by brachytherapy. Eight patients were treated solely with brachytherapy, all receiving 24-45 Gy in 3-10 sessions. Forty-one patients were treated with ERT alone receiving a median TED of 57.3 Gy (range, 49.8-62.5 Gy). Forty-two patients were treated by CMT with a median equivalent dose of 50 Gy (range, 40-60 Gy) given by ERT and 14.8 Gy by brachytherapy (range, 3-29.6 Gy). Multivariate analyses were performed using the Cox regression proportional hazards model. Results: The 5-year actuarial overall survival rate, disease specific survival rate and local failure-free survival (LFFS) rate for the whole group were 30%, 33.3% and 37.8%, respectively. The 3-year LFFS rates of rT1, rT2, and rT3 diseases were 64%, 61.5%, and 18.4%, respectively (p = 0.001). Of the 8 patients treated with brachytherapy alone, 4 failed locally. Further analyses were concentrated on the ERT (41 patients) and CMT (42 patients) groups. The 3-year LFFS rates of rT1, rT2, and rT3 diseases were 66.7%, 66.7%, and 18.4%, respectively (p 0

Monotherapy of androgen deprivation therapy versus radical prostatectomy among veterans with localized prostate cancer: comparative effectiveness analysis of retrospective cohorts

Directory of Open Access Journals (Sweden)

Liu J

2012-05-01

high a mortality risk as those using radical prostatectomy (hazards ratio 3.388, 95% confidence interval 1.094–10.492, P = 0.034.Conclusion: After propensity score matching, overall three-year survival rate following radical prostatectomy among patients with localized prostate cancer was significantly higher than that after primary androgen deprivation therapy.Keywords: prostate cancer, primary androgen deprivation therapy, radical prostatectomy, survival rate

Joint Estimation of Cardiac Toxicity and Recurrence Risks After Comprehensive Nodal Photon Versus Proton Therapy for Breast Cancer

Energy Technology Data Exchange (ETDEWEB)

Stick, Line B., E-mail: line.bjerregaard.stick@regionh.dk [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Niels Bohr Institute, Faculty of Science, University of Copenhagen, Copenhagen (Denmark); Yu, Jen [Maryland Proton Treatment Center, University of Maryland School of Medicine, Baltimore, Maryland (United States); Maraldo, Maja V. [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Aznar, Marianne C. [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Nuffield Department of Population Health, University of Oxford, Oxford (United Kingdom); Pedersen, Anders N. [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Bentzen, Søren M. [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Maryland Proton Treatment Center, University of Maryland School of Medicine, Baltimore, Maryland (United States); Greenebaum Comprehensive Cancer Center and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland (United States); Vogelius, Ivan R. [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark)

2017-03-15

Purpose: The study aims to perform joint estimation of the risk of recurrence caused by inadequate radiation dose coverage of lymph node targets and the risk of cardiac toxicity caused by radiation exposure to the heart. Delivered photon plans are compared with realistic proton plans, thereby providing evidence-based estimates of the heterogeneity of treatment effects in consecutive cases for the 2 radiation treatment modalities. Methods and Materials: Forty-one patients referred for postlumpectomy comprehensive nodal photon irradiation for left-sided breast cancer were included. Comparative proton plans were optimized by a spot scanning technique with single-field optimization from 2 en face beams. Cardiotoxicity risk was estimated with the model of Darby et al, and risk of recurrence following a compromise of lymph node coverage was estimated by a linear dose-response model fitted to the recurrence data from the recently published EORTC (European Organisation for Research and Treatment of Cancer) 22922/10925 and NCIC-CTG (National Cancer Institute of Canada Clinical Trials Group) MA.20 randomized controlled trials. Results: Excess absolute risk of cardiac morbidity was small with photon therapy at an attained age of 80 years, with median values of 1.0% (range, 0.2%-2.9%) and 0.5% (range, 0.03%-1.0%) with and without cardiac risk factors, respectively, but even lower with proton therapy (0.13% [range, 0.02%-0.5%] and 0.06% [range, 0.004%-0.3%], respectively). The median estimated excess absolute risk of breast cancer recurrence after 10 years was 0.10% (range, 0.0%-0.9%) with photons and 0.02% (range, 0.0%-0.07%) with protons. The association between age of the patient and benefit from proton therapy was weak, almost non-existing (Spearman rank correlations of −0.15 and −0.30 with and without cardiac risk factors, respectively). Conclusions: Modern photon therapy yields limited risk of cardiac toxicity in most patients, but proton therapy can reduce the

EUD-based biological optimization for carbon ion therapy

International Nuclear Information System (INIS)

Brüningk, Sarah C.; Kamp, Florian; Wilkens, Jan J.

2015-01-01

therapy, the optimization by biological objective functions resulted in slightly superior treatment plans in terms of final EUD for the organs at risk (OARs) compared to voxel-based optimization approaches. This observation was made independent of the underlying objective function metric. An absolute gain in OAR sparing was observed for quadratic objective functions, whereas intersecting DVHs were found for logistic approaches. Even for considerable under- or overestimations of the used effect- or dose–volume parameters during the optimization, treatment plans were obtained that were of similar quality as the results of a voxel-based optimization. Conclusions: EUD-based optimization with either of the presented concepts can successfully be applied to treatment plan optimization. This makes EUE-based optimization for carbon ion therapy a useful tool to optimize more specifically in the sense of biological outcome while voxel-to-voxel variations of the biological effectiveness are still properly accounted for. This may be advantageous in terms of computational cost during treatment plan optimization but also enables a straight forward comparison of different fractionation schemes or treatment modalities

Survey of expert opinions and related recommendations regarding bridging therapy using hypomethylating agents followed by allogeneic transplantation for high-risk MDS.

Science.gov (United States)

Sohn, Sang Kyun; Moon, Joon Ho

2015-08-01

According to current guidelines on therapeutic strategies for myelodysplastic syndrome (MDS), cytoreductive therapies before allogeneic stem cell transplantation (SCT) are not widely recommended for patients with high-risk MDS or refractory anemia with excess blasts (RAEB) who are eligible for allogeneic SCT because of controversial evidence on the role of such therapies. Yet, while treatment with hypomethylating agents (HMAs) has a critical limitation in eradicating MDS clones, the use of HMA treatment as a bridge to allogeneic SCT has become a focus with the hope of improving the SCT outcome based on the chance of achieving complete remission or reducing the blast percentage safely and effectively before allogeneic SCT. However, a consensus needs to be established on the use of HMAs as a bridging therapy for high-risk MDS or RAEB. Thus, the Korean AML/MDS working party group surveyed 34 Korean MDS experts on their bridging therapies for high-risk MDS. Accordingly, this paper presents the survey questionnaire and resulting data, along with a summary of the consensus and related recommendations regarding strategies using HMA treatment and allogeneic SCT based on reported studies and the current survey results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

HIV and antiretroviral therapy: lipid abnormalities and associated cardiovascular risk in HIV-infected patients.

Science.gov (United States)

Kotler, Donald P

2008-09-01

It has been demonstrated that patients on highly active antiretroviral therapy are at increased risk for developing metabolic abnormalities that include elevated levels of serum triglycerides and low-density lipoprotein cholesterol and reduced levels of high-density lipoprotein cholesterol. This dyslipidemia is similar to that seen in the metabolic syndrome, raising the concern that highly active antiretroviral therapy also potentially increases the risk for cardiovascular complications. This paper reviews the contribution of both HIV infection and the different components of highly active antiretroviral therapy to dyslipidemia and the role of these abnormalities toward increasing the risk of cardiovascular disease in HIV-infected patients; therapeutic strategies to manage these risks are also considered.

Current concepts in F18 FDG PET/CT-based Radiation Therapy planning for Lung Cancer

Directory of Open Access Journals (Sweden)

Percy eLee

2012-07-01

Full Text Available Radiation therapy is an important component of cancer therapy for early stage as well as locally advanced lung cancer. The use of F18 FDG PET/CT has come to the forefront of lung cancer staging and overall treatment decision-making. FDG PET/CT parameters such as standard uptake value and metabolic tumor volume provide important prognostic and predictive information in lung cancer. Importantly, FDG PET/CT for radiation planning has added biological information in defining the gross tumor volume as well as involved nodal disease. For example, accurate target delineation between tumor and atelectasis is facilitated by utilizing PET and CT imaging. Furthermore, there has been meaningful progress in incorporating metabolic information from FDG PET/CT imaging in radiation treatment planning strategies such as radiation dose escalation based on standard uptake value thresholds as well as using respiratory gated PET and CT planning for improved target delineation of moving targets. In addition, PET/CT based follow-up after radiation therapy has provided the possibility of early detection of local as well as distant recurrences after treatment. More research is needed to incorporate other biomarkers such as proliferative and hypoxia biomarkers in PET as well as integrating metabolic information in adaptive, patient-centered, tailored radiation therapy.

The benefits and risks of testosterone replacement therapy: a review

Directory of Open Access Journals (Sweden)

Nazem Bassil

2009-06-01

Full Text Available Nazem Bassil1, Saad Alkaade2, John E Morley1,31Division of Geriatric Medicine; 2Internal Medicine, Saint Louis University Health Sciences Center, St. Louis, Missouri, USA; 3GRECC, VA Medical Center, St. Louis, Missouri, USAAbstract: Increased longevity and population aging will increase the number of men with late onset hypogonadism. It is a common condition, but often underdiagnosed and undertreated. The indication of testosterone-replacement therapy (TRT treatment requires the presence of low testosterone level, and symptoms and signs of hypogonadism. Although controversy remains regarding indications for testosterone supplementation in aging men due to lack of large-scale, long-term studies assessing the benefits and risks of testosterone-replacement therapy in men, reports indicate that TRT may produce a wide range of benefits for men with hypogonadism that include improvement in libido and sexual function, bone density, muscle mass, body composition, mood, erythropoiesis, cognition, quality of life and cardiovascular disease. Perhaps the most controversial area is the issue of risk, especially possible stimulation of prostate cancer by testosterone, even though no evidence to support this risk exists. Other possible risks include worsening symptoms of benign prostatic hypertrophy, liver toxicity, hyperviscosity, erythrocytosis, worsening untreated sleep apnea or severe heart failure. Despite this controversy, testosterone supplementation in the United States has increased substantially over the past several years. The physician should discuss with the patient the potential benefits and risks of TRT. The purpose of this review is to discuss what is known and not known regarding the benefits and risks of TRT.Keywords: hypogonadism, testosterone replacement therapy, erectile dysfunction, osteoporosis, cardiovascular disease

Delayed esophageal perforation from stereotactic body radiation therapy for locally recurrent central nonsmall cell lung cancer

Directory of Open Access Journals (Sweden)

Sandeep Sainathan

2014-01-01

Full Text Available Stereotactic body radiation therapy (SBRT is a novel form of external beam radiation therapy. It is used to treat early and locally recurrent nonsmall cell lung cancer (NSLC in medically inoperable patients. It uses high dose, hypofractionated radiotherapy, with targeting of the tumor by precise spatial localization, thus minimizing injury to surrounding tissues. It can be safely used to ablate NSLC in both central and peripheral locations. We present two cases of delayed esophageal perforation after SBRT for locally recurrent central NSLC. The perforations occurred several months after the therapy. They were treated with covered esophageal stents, with mortality, due to the perforation in one of the patients. SBRT should be judiciously used to ablate centrally located NSLC and patients who develop episodes of esophagitis during or after SBRT, need to be closely followed with endoscopy to look for esophageal ulcerations. These ulcers should be closely followed for healing as these may degenerate into full thickness perforations several months after SBRT.

Risks and benefits of hormone therapy: has medical dogma now been overturned?

Science.gov (United States)

Shapiro, S; de Villiers, T J; Pines, A; Sturdee, D W; Baber, R J; Panay, N; Stevenson, J C; Mueck, A O; Burger, H G

2014-06-01

In an integrated overview of the benefits and risks of menopausal hormone therapy (HT), the Women's Health Initiative (WHI) investigators have claimed that their 'findings … do not support use of this therapy for chronic disease prevention'. In an accompanying editorial, it was claimed that 'the WHI overturned medical dogma regarding menopausal [HT]'. To evaluate those claims. Epidemiological criteria of causation were applied to the evidence. A 'global index' purporting to summarize the overall benefit versus the risk of HT was not valid, and it was biased. For coronary heart disease, an increased risk in users of estrogen plus progestogen (E + P), previously reported by the WHI, was not confirmed. The WHI study did not establish that E+ P increases the risk of breast cancer; the findings suggest that unopposed estrogen therapy (ET) does not increase the risk, and may even reduce it. The findings for stroke and pulmonary embolism were compatible with an increased risk, and among E+ P users there were credible reductions in the risk of colorectal and endometrial cancer. For E+ P and ET users, there were credible reductions in the risk of hip fracture. Under 'worst case' and 'best case' assumptions, the changes in the incidence of the outcomes attributable to HT were minor. Over-interpretation and misrepresentation of the WHI findings have damaged the health and well-being of menopausal women by convincing them and their health professionals that the risks of HT outweigh the benefits.

The interplay between gait, falls and cognition: can cognitive therapy reduce fall risk?

Science.gov (United States)

Segev-Jacubovski, Orit; Herman, Talia; Yogev-Seligmann, Galit; Mirelman, Anat; Giladi, Nir; Hausdorff, Jeffrey M

2011-01-01

In this article, we briefly summarize the incidence and significant consequences of falls among older adults, the insufficient effectiveness of commonly used multifactorial interventions and the evidence linking falls and cognitive function. Recent pharmacologic and nonpharmacologic studies that evaluated the effects of cognitive therapy on fall risk are reviewed. The results of this article illustrate the potential utility of multiple, diverse forms of cognitive therapy for reducing fall risk. The article also indicates that large-scale, randomized controlled trials are warranted and that additional research is needed to better understand the pathophysiologic mechanisms underlying the interplay between human mobility, fall risk and cognitive function. Nonetheless, we suggest that multimodality interventions that combine motor and cognitive therapy should, eventually, be incorporated into clinical practice to enable older adults and patients to move safer and with a reduced fall risk. PMID:21721921

Applying a machine learning model using a locally preserving projection based feature regeneration algorithm to predict breast cancer risk

Science.gov (United States)

Heidari, Morteza; Zargari Khuzani, Abolfazl; Danala, Gopichandh; Mirniaharikandehei, Seyedehnafiseh; Qian, Wei; Zheng, Bin

2018-03-01

Both conventional and deep machine learning has been used to develop decision-support tools applied in medical imaging informatics. In order to take advantages of both conventional and deep learning approach, this study aims to investigate feasibility of applying a locally preserving projection (LPP) based feature regeneration algorithm to build a new machine learning classifier model to predict short-term breast cancer risk. First, a computer-aided image processing scheme was used to segment and quantify breast fibro-glandular tissue volume. Next, initially computed 44 image features related to the bilateral mammographic tissue density asymmetry were extracted. Then, an LLP-based feature combination method was applied to regenerate a new operational feature vector using a maximal variance approach. Last, a k-nearest neighborhood (KNN) algorithm based machine learning classifier using the LPP-generated new feature vectors was developed to predict breast cancer risk. A testing dataset involving negative mammograms acquired from 500 women was used. Among them, 250 were positive and 250 remained negative in the next subsequent mammography screening. Applying to this dataset, LLP-generated feature vector reduced the number of features from 44 to 4. Using a leave-onecase-out validation method, area under ROC curve produced by the KNN classifier significantly increased from 0.62 to 0.68 (p breast cancer detected in the next subsequent mammography screening.

Submandibular gland-sparing radiation therapy for locally advanced oropharyngeal squamous cell carcinoma: patterns of failure and xerostomia outcomes

International Nuclear Information System (INIS)

Gensheimer, Michael F; Liao, Jay J; Garden, Adam S; Laramore, George E; Parvathaneni, Upendra

2014-01-01

Saliva from submandibular glands (SMG) is necessary to minimize xerostomia. It is unclear whether SMG can be safely spared in patients undergoing bilateral neck radiotherapy for locally advanced oropharyngeal cancer without increasing the risk of marginal recurrence. We evaluated the outcomes of contralateral submandibular gland (cSMG) sparing intensity-modulated radiation therapy (IMRT). All patients with stage III/IV oropharyngeal squamous cell carcinoma treated with bilateral neck IMRT from 2006–2012 at our institution were included. Appropriately selected patients with favorable primary tumor characteristics and no definite contralateral neck disease were treated with cSMG-sparing IMRT. Patterns of failure and xerostomia outcomes were retrospectively analyzed. 114 patients were treated. 89% had stage IV disease and 89% received definitive radiation therapy. 76 patients (67%) received cSMG sparing IMRT. With a median follow-up of 30 months, there were 10 local, 9 regional, and 10 distant recurrences. 2-year overall survival was 86% and 2-year loco-regional control was 87%. In cSMG spared patients, the mean cSMG dose was 30.7 Gy. Late grade 2+ xerostomia was significantly reduced in the cSMG spared group compared to those without SMG sparing (6 months: 23% vs. 72%, 12 months: 6% vs. 41%, 24 months: 3% vs. 36%, all p < 0.0007). There were no peri-SMG marginal recurrences in the cSMG-spared cohort. cSMG sparing IMRT did not increase marginal failures in this series of locally advanced oropharyngeal SCC patients. Xerostomia was significantly reduced in cSMG spared patients

Second Malignancies After Adjuvant Radiation Therapy for Early Stage Breast Cancer: Is There Increased Risk With Addition of Regional Radiation to Local Radiation?

Energy Technology Data Exchange (ETDEWEB)

Hamilton, Sarah Nicole [Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia (Canada); Tyldesley, Scott, E-mail: styldesl@bccancer.bc.ca [Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia (Canada); Li, Dongdong [Cancer Control Research Department, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia (Canada); Olson, Robert [Department of Radiation Oncology, British Columbia Cancer Agency-Centre for the North, Prince George, British Columbia (Canada); McBride, Mary [Cancer Control Research Department, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia (Canada)

2015-04-01

Purpose: This study was undertaken to determine whether there was an increased risk of second malignancies (SM), particularly lung cancer, in early stage breast cancer patients treated with the addition of nodal fields to breast and/or chest wall radiation therapy (RT). Materials and Methods: Subjects were stage I/II female breast cancer patients 20 to 79 years of age, diagnosed between 1989 and 2005 and treated with adjuvant RT at our institution. Patients were included if they survived and did not have SM within 3 years of diagnosis. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated to compare SM incidence to cancer incidence in the general sex- and age-matched populations. Secondary malignancy risks in patients treated with local RT (LRT) to the breast/chest wall were compared to those in patients treated with locoregional RT (LRRT) to the breast/chest wall and regional nodes, using multivariate regression analysis (MVA) to account for covariates. Results: The cohort included 12,836 patients with a median follow-up of 8.4 years. LRRT was used in 18% of patients. The SIR comparing patients treated with LRT to the general population was 1.29 (CI: 1.21-1.38). No statistically significant increased incidence of in-field malignancies (SIR, 1.04; CI: 0.87-1.23) and lung cancers (SIR, 1.06; CI: 0.88-1.26) was detected. The SIR comparing patients treated with LRRT to the general population was 1.39 (CI: 1.17-1.64). No statistically significant increased incidence of in-field malignancies (SIR, 1.26; CI: 0.77-1.94) and lung cancers (SIR, 1.27; CI: 0.76-1.98) was detected. On MVA comparing LRRT to LRT, the adjusted hazard ratio was 1.20 for in-field malignancies (CI: 0.68-2.16) and 1.26 for lung cancer (CI: 0.67-2.36). The excess attributable risk (EAR) to regional RT was 3.1 per 10,000 person years (CI: −8.7 to 9.9). Conclusions: No statistically significant increased risk of second malignancy was detected after LRRT relative to

Three-dimensional conformal radiation therapy: the tomo-therapy approach

International Nuclear Information System (INIS)

Linthout, N.; Verellen, D.; Coninck, P. de; Bel, A.; Storme, G.

2000-01-01

Conformal radiation therapy allows the possibility of delivering high doses at the tumor volume whilst limiting the dose to the surrounding tissues and diminishing the secondary effects. With the example of the conformal radiation therapy used at the AZ VU8 (3DCRT and tomo-therapy), two treatment plans of a left ethmoid carcinoma will be evaluated and discussed in detail. The treatment of ethmoid cancer is technically difficult for both radiation therapy and surgery because of the anatomic constraints and patterns of local spread. A radiation therapy is scheduled to be delivered after surgical resection of the tumor. The treatment plan for the radiation therapy was calculated on a three-dimensional (3D) treatment planning system based on virtual simulation with a beam's eye view: George Sherouse's Gratis. An effort was made to make the plan as conformal and as homogeneous as possible to deliver a dose of 66 Gy in 33 fractions at the tumor bed with a maximum dose of 56 Gy to the right optic nerve and the chiasma. To establish the clinical utility and potential advantages of tomo-therapy over 3DCRT for ethmoid carcinoma, the treatment of this patient was also planned with Peacock Plant. For both treatment plans the isodose distributions and cumulative dose volume histograms (CDVH) were computed. Superimposing the CDVHs yielded similar curves for the target and an obvious improvement for organs at risk such as the chiasma, brainstem and the left eye when applying tomo-therapy. These results have also been reflected in the tumor control probabilities (equal for both plans) and the normal tissue complication probabilities (NTCP), yielding significant reductions in NTCP for tomo-therapy. The probability of uncomplicated tumor control was 52.7% for tomo-therapy against 38.3% for 3DCRT. (authors)

Systemic sclerosis and localized scleroderma--current concepts and novel targets for therapy.

Science.gov (United States)

Distler, Oliver; Cozzio, Antonio

2016-01-01

Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Skin and organ fibrosis are key manifestations of SSc, for which no generally accepted therapy is available. Thus, there is a high unmet need for novel anti-fibrotic therapeutic strategies in SSc. At the same time, important progress has been made in the identification and characterization of potential molecular targets in fibrotic diseases over the recent years. In this review, we have selected four targeted therapies, which are tested in clinical trials in SSc, for in depths discussion of their preclinical characterization. Soluble guanylate cyclase (sGC) stimulators such as riociguat might target both vascular remodeling and tissue fibrosis. Blockade of interleukin-6 might be particularly promising for early inflammatory stages of SSc. Inhibition of serotonin receptor 2b signaling links platelet activation to tissue fibrosis. Targeting simultaneously multiple key molecules with the multityrosine kinase-inhibitor nintedanib might be a promising approach in complex fibrotic diseases such as SSc, in which many partially independent pathways are activated. Herein, we also give a state of the art overview of the current classification, clinical presentation, diagnostic approach, and treatment options of localized scleroderma. Finally, we discuss whether the novel targeted therapies currently tested in SSc could be used for localized scleroderma.

[Proangiogenic cell-based therapy for treatment of ischemic diseases].

Science.gov (United States)

Silvestre, Jean-Sébastien

2009-11-01

The application of endothelial progenitor cells (EPC) cell-based therapy for regenerative medicine constitutes a promising therapeutic avenue for the treatment of cardiovascular diseases. Based on experimental studies demonstrating that bone marrow-, blood- or tissue-derived stem/progenitor cells improve the functional recovery after ischemia, clinical trials were initiated to address this new therapeutic concept. Although autolougous cell therapy was shown to improve perfusion and function of ischemic tissues, a number of issues remain to be adressed. The nature of the mobilizing, migratory and homing signals, and the mechanisms of action need to be identified and further defined. In addition, strategies to enhance homing, survival and therapeutic potential of EPC need to be developped to improve therapeutic effect and counteract EPC dysfunction in aged patients with cardiovascular risk factors. The present review article will discuss the mechanisms of action of different types of adult stem cells and several approaches to improve their therapeutic efficiency.

Study of a risk-based piping inspection guideline system.

Science.gov (United States)

Tien, Shiaw-Wen; Hwang, Wen-Tsung; Tsai, Chih-Hung

2007-02-01

A risk-based inspection system and a piping inspection guideline model were developed in this study. The research procedure consists of two parts--the building of a risk-based inspection model for piping and the construction of a risk-based piping inspection guideline model. Field visits at the plant were conducted to develop the risk-based inspection and strategic analysis system. A knowledge-based model had been built in accordance with international standards and local government regulations, and the rational unified process was applied for reducing the discrepancy in the development of the models. The models had been designed to analyze damage factors, damage models, and potential damage positions of piping in the petrochemical plants. The purpose of this study was to provide inspection-related personnel with the optimal planning tools for piping inspections, hence, to enable effective predictions of potential piping risks and to enhance the better degree of safety in plant operations that the petrochemical industries can be expected to achieve. A risk analysis was conducted on the piping system of a petrochemical plant. The outcome indicated that most of the risks resulted from a small number of pipelines.

Localized Scleroderma: A Clinical Review.

Science.gov (United States)

Tratenberg, Mark; Gutwein, Farrah; Rao, Varuni; Sperber, Kirk; Wasserrman, Amy; Ash, Julia

2017-01-01

Localized scleroderma (LS) is characterized by excessive collagen deposition leading to thickening of the dermis, subcutaneous tissue or both. The outcome for most patients with localized scleroderma is directly related to the type and stage of the affected tissue. The major challenge for untreated patients is not increased mortality risk, rather deformity and growth defects from skin, muscle and bone abnormalities. Treatment is individualized to type and stage of the lesion and may include pharmacologic and non-pharmacologic therapies. Among the pharmacologic modalities, methotrexate with systemic glucocorticoids is currently the mainstay of treatment. More controlled trials are needed to determine the length of treatment and the maintenance dose of this combination therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Reduction of Risk Factors in Patients with Behavioral Dysphonia After Vocal Group Therapy.

Science.gov (United States)

Silva, Wégina Jordâna Nascimento da; Lopes, Leonardo Wanderley; Macedo, Anny Elizabety Ramalho de; Costa, Denise Batista da; Almeida, Anna Alice Figueiredo de

2017-01-01

The origin and development of dysphonia, particularly behavioral dysphonia, is associated with several risk factors. Here, we verified the effectiveness of group therapy in reducing the risk factors, and established the association between risk factors and sex, age, profession, and diagnosis of laryngeal disorders in patients with behavioral dysphonia. This is a descriptive, quantitative, field intervention study. Participants (n = 26, adult patients of both sexes), with a diagnosis of behavioral dysphonia, received group therapy intervention. Data for risk factors were collected pre- and posttherapy using the Vocal Screening Protocol. The data were analyzed using descriptive and inferential statistics (Student t test, chi-squared test or Spearman correlation test). The majority (80.8%, n = 21) of patients were female, 65.4% (n = 17) were not in a vocal profession, and 42.3% (n = 11) presented with a lesion in the membranous portion of the vocal fold. The number of personal risk factors decreased after group therapy (P = 0.04). In addition, age was correlated with total (P = 0.001), environmental (P = 0.002), and personal (P = 0.003) vocal risk factors posttherapy. This study revealed an association between the reduction of personal risk factors and vocal group therapy, and a correlation between age and total, environmental, and personal vocal risk factors posttherapy. Thus, maintenance and origins of the behaviors that modify the behavioral aspects of the participants directly influence the production of individual vocal habits. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

The implementation of local wisdom in reducing natural disaster risk: a case study from West Sumatera

Science.gov (United States)

Zulfadrim, Z.; Toyoda, Y.; Kanegae, H.

2018-01-01

The purpose of this paper is to introduce some local wisdoms in West Sumatra and propose their challenges that modern values have degraded its knowledge. In a contemporary context, traditional stories (written and oral stories) still relevant to be used and internalized in disaster risk reduction. Traditional knowledge or local wisdom is a system of knowledge derived from long experienced process in the past, adopted and handed over to next generation through evolutionary process. Indigenous or traditional knowledge can be practiced in understanding the nature of natural disaster, to propose the best action in mitigation, to respond in emergency phase, and to suggest more option for recovery process based on previous experience. The paper based on four weeks field research in west Sumatra which is known with their natural hazards due to its geographical location. In the beginning, this paper discusses the nature of local wisdom and how it can be matched in disaster management, then continues to the specific case how the traditional stories in West Sumatera can be internalized and integrated with contemporary disaster risk reduction. This paper proves that local wisdom can be useful as an effective instrument to deal with natural disaster or natural hazard.

A Systematic Overview of Radiation Therapy Effects in Prostate Cancer

International Nuclear Information System (INIS)

Nilsson, Sten; Norlen, Bo Johan; Widmark, Anders

2004-01-01

A systematic review of radiation therapy trials in prostate cancer has been performed according to principles adopted by the Swedish Council of Technology Assessment in Health Care (SBU). This synthesis of the literature is based on data from one meta-analysis, 30 randomized trials, many dealing with hormonal therapy, 55 prospective trials, and 210 retrospective studies. Totally the studies included 152,614 patients. There is a lack of properly controlled clinical trials in most important aspects of radiation therapy in prostate cancer. The conclusions reached can be summarized as follows: There are no randomized studies that compare the outcome of surgery (radical prostatectomy) with either external beam radiotherapy or brachytherapy for patients with clinically localized low-risk prostate cancer. However, with the advent of widely accepted prognostic markers for prostate cancer (pre-treatment PSA, Gleason score, and T-stage), such comparisons have been made possible. There is substantial documentation from large single-institutional and multi-institutional series on patients with this disease category (PSA T2) disease, i.e. patients normally not suited for surgery, benefit from higher than conventional total dose. No overall survival benefit has yet been shown. Dose escalation to patients with intermediate-risk or high-risk disease can be performed with 3D conformal radiotherapy (photon or proton) boost, with Ir-192 high dose rate brachytherapy boost, or brachytherapy boost with permanent seed implantation. Despite an increased risk of urinary tract and/or rectal side effects, dose-escalated therapy can generally be safely delivered with all three techniques. There is some evidence that 3D conformal radiotherapy results in reduced late rectal toxicity and acute anal toxicity compared with radiotherapy administered with non-conformal treatment volumes. There is some evidence that postoperative external beam radiotherapy after radical prostatectomy in patients with

Menopausal hormone therapy and risk of melanoma: Do estrogens and progestins have a different role?

Science.gov (United States)

Botteri, Edoardo; Støer, Nathalie C; Sakshaug, Solveig; Graff-Iversen, Sidsel; Vangen, Siri; Hofvind, Solveig; Ursin, Giske; Weiderpass, Elisabete

2017-11-01

The association between use of menopausal hormone therapy (HT) and occurrence of skin malignant melanoma (SMM) is controversial. We investigated the issue in a nationwide cohort of 684,696 Norwegian women, aged 45-79 years, followed from 2004 to 2008. The study was based on linkage between Norwegian population registries. Multivariable Poisson regression models were used to estimate the effect of HT use, different HT types, routes of administration and doses of estrogen and progestin on the risk of SMM. During the median follow-up of 4.8 years, 178,307 (26%) women used HT, and 1,476 incident SMM cases were identified. Current use of HT was associated with increased risk of SMM (rate ratios (RR) = 1.19; 95% confidence interval (CI) 1.03-1.37). Plain estrogen therapy was associated with an increased risk of SMM (RR 1.45; 95% CI 1.21-1.73), both for oral (RR 1.45; 95% CI 1.09-1.93) and vaginal (RR 1.44; 95% CI 1.14-1.84) formulations, while combined estrogen and progestin therapy (EPT) was not (RR 0.91; 95% CI 0.70-1.19). We performed a dose-response analysis of estrogen and progestin in women using tablets, and found that use of estrogens was associated with increased risk (RR 1.24; 95% CI 1.00-1.53 per 1 mg/day) and use of progestins with decreased risk (RR 0.71; 95% CI 0.57-0.89 per 10 mg/month) of SMM. In conclusion, estrogens were associated with increased risk of SMM, while combinations of estrogens and progestins were not. Our results suggest that estrogens and progestins might affect the risk of SMM in opposite ways. © 2017 UICC.

Estimating risks of importation and local transmission of Zika virus infection

Directory of Open Access Journals (Sweden)

Kyeongah Nah

2016-04-01

Full Text Available Background. An international spread of Zika virus (ZIKV infection has attracted global attention. ZIKV is conveyed by a mosquito vector, Aedes species, which also acts as the vector species of dengue and chikungunya viruses. Methods. Arrival time of ZIKV importation (i.e., the time at which the first imported case was diagnosed in each imported country was collected from publicly available data sources. Employing a survival analysis model in which the hazard is an inverse function of the effective distance as informed by the airline transportation network data, and using dengue and chikungunya virus transmission data, risks of importation and local transmission were estimated. Results. A total of 78 countries with imported case(s have been identified, with the arrival time ranging from 1 to 44 weeks since the first ZIKV was identified in Brazil, 2015. Whereas the risk of importation was well explained by the airline transportation network data, the risk of local transmission appeared to be best captured by additionally accounting for the presence of dengue and chikungunya viruses. Discussion. The risk of importation may be high given continued global travel of mildly infected travelers but, considering that the public health concerns over ZIKV infection stems from microcephaly, it is more important to focus on the risk of local and widespread transmission that could involve pregnant women. The predicted risk of local transmission was frequently seen in tropical and subtropical countries with dengue or chikungunya epidemic experience.

Pre- and post-radiotherapy computed tomography in laryngeal cancer: imaging-based prediction of local failure

International Nuclear Information System (INIS)

Pameijer, Frank A.; Hermans, Robert; Mancuso, Anthony A.; Mendenhall, William M.; Parsons, James T.; Stringer, Scott P.; Kubilis, Paul S.; Tinteren, Harm van

1999-01-01

Purpose: To determine if pre-radiotherapy (RT) and/or post-radiotherapy computed tomography (CT) can predict local failure in patients with laryngeal carcinoma treated with definitive RT. Methods and Materials: The pre- and post-RT CT examinations of 59 patients (T3 glottic carcinoma [n = 30] and T1-T4 supraglottic carcinoma [n = 29]) were reviewed. For each patient, the first post-RT CT study between 1 and 6 months after irradiation was used. All patients were treated with definitive hyperfractionated twice-daily continuous-course irradiation to a total dose of 6,720-7,920 cGy, and followed-up clinically for at least 2 years after completion of RT. Local control was defined as absence of primary tumor recurrence and a functioning larynx. On the pre-treatment CT study, each tumor was assigned a high-or low-risk profile for local failure after RT. The post-RT CT examinations were evaluated for post-treatment changes using a three-point post-RT CT-score: 1 = expected post-RT changes; 2 = focal mass with a maximal diameter of 1 cm, or < 50% estimated tumor volume reduction. Results: The local control rates at 2 years post-RT based on pre-treatment CT evaluation were 88% for low pre-treatment risk profile patients (95% CI: 66-96%) and 34% (95% CI: 19-50%) for high pre-treatment risk profile patients (risk ratio 6.583; 95% CI: 2.265-9.129; p = 0.0001). Based on post-treatment CT, the local control rates at 2 years post-RT were 94% for score 1, 67% for score 2, and 10% for score 3 (risk ratio 4.760; 95% CI: 2.278-9.950 p 0.0001). Post-RT CT scores added significant information to the pre-treatment risk profiles on prognosis. Conclusions: Pre-treatment CT risk profiles, as well as post-RT CT evaluation can identify patients, irradiated for laryngeal carcinomas, at high risk for developing local failure. When the post-RT CT score is available, it proves to be an even better prognosticator than the pre-treatment CT-risk profile

A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Harris, Jeremy P. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Murphy, James D. [Department of Radiation Medicine and Applied Science, University of California– San Diego, Moores Cancer Center, La Jolla, California (United States); Hanlon, Alexandra L. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); University of Pennsylvania School of Nursing, Philadelphia, Pennsylvania (United States); Le, Quynh-Thu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Loo, Billy W., E-mail: BWLoo@Stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Diehn, Maximilian, E-mail: diehn@Stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California (United States)

2014-03-15

Purpose: Concerns have been raised about the potential for worse treatment outcomes because of dosimetric inaccuracies related to tumor motion and increased toxicity caused by the spread of low-dose radiation to normal tissues in patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy (IMRT). We therefore performed a population-based comparative effectiveness analysis of IMRT, conventional 3-dimensional conformal radiation therapy (3D-CRT), and 2-dimensional radiation therapy (2D-RT) in stage III NSCLC. Methods and Materials: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify a cohort of patients diagnosed with stage III NSCLC from 2002 to 2009 treated with IMRT, 3D-CRT, or 2D-RT. Using Cox regression and propensity score matching, we compared survival and toxicities of these treatments. Results: The proportion of patients treated with IMRT increased from 2% in 2002 to 25% in 2009, and the use of 2D-RT decreased from 32% to 3%. In univariate analysis, IMRT was associated with improved overall survival (OS) (hazard ratio [HR] 0.90, P=.02) and cancer-specific survival (CSS) (HR 0.89, P=.02). After controlling for confounders, IMRT was associated with similar OS (HR 0.94, P=.23) and CSS (HR 0.94, P=.28) compared with 3D-CRT. Both techniques had superior OS compared with 2D-RT. IMRT was associated with similar toxicity risks on multivariate analysis compared with 3D-CRT. Propensity score matched model results were similar to those from adjusted models. Conclusions: In this population-based analysis, IMRT for stage III NSCLC was associated with similar OS and CSS and maintained similar toxicity risks compared with 3D-CRT.

Positioning SGLT2 Inhibitors/Incretin-Based Therapies in the Treatment Algorithm.

Science.gov (United States)

Wilding, John P H; Rajeev, Surya Panicker; DeFronzo, Ralph A

2016-08-01

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are the most recent addition to the therapeutic options available for the treatment of type 2 diabetes and became available after the introduction of incretin-based therapies, dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs). These agents have potential advantages with regard to their weight loss-promoting effect, low risk of hypoglycemia, reduction in blood pressure, and reduction in cardiovascular events in high-risk patients (with empagliflozin). Apart from these clinically important outcomes, they may also correct core defects present in type 2 diabetes (i.e., improvement in β-cell function and insulin sensitivity). They do, however, have some adverse effects, notably, nausea with GLP-1 RAs and genital tract infections and potential for volume depletion with SGLT2i. Whether incretin-based therapies are associated with an increased risk of pancreatitis is unclear. Most recently, diabetic ketoacidosis has been reported with SGLT2i. Therefore, a key clinical question in relation to guidelines is whether these clinical advantages, in the context of the adverse effect profile, outweigh the additional cost compared with older, more established therapies. This article reviews the therapeutic rationale for the use of these newer drugs for diabetes treatment, considers their place in current guidelines, and discusses how this may change as new data emerge about their long-term efficacy and safety from ongoing outcome trials. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Tumor Volume Changes on 1.5 Tesla Endorectal MRI During Neoadjuvant Androgen Suppression Therapy for Higher-Risk Prostate Cancer and Recurrence in Men Treated Using Radiation Therapy Results of the Phase II CALGB 9682 Study

International Nuclear Information System (INIS)

D'Amico, Anthony V.; Halabi, Susan; Tempany, Clare; Titelbaum, David; Philips, George K.; Loffredo, Marian; McMahon, Elizabeth; Sanford, Ben; Vogelzang, Nicholas J.; Small, Eric J.

2008-01-01

Purpose: We prospectively determined whether the change in tumor volume (TV) during 2 months of neoadjuvant androgen suppression therapy (nAST) measured using conventional 1.5 Tesla endorectal magnetic resonance imaging (eMRI) was associated with the risk of recurrence after radiation (RT) and 6 months of AST. Patients and Methods: Between 1997 and 2001, 180 men with clinical stage T1c-T3cN0M0 adenocarcinoma of the prostate were registered. Fifteen were found to be ineligible and the institutional MR radiologist could not assess the TV in 32, leaving 133 for analysis. Multivariable Cox regression analysis was used to assess whether a significant association existed between eMRI-defined TV progression during nAST and time to recurrence adjusting for prostate-specific antigen (PSA) level, Gleason score (8 to 10 or 7 vs. 6 or less) and stage (T3 vs. T1-2). Results: After a median follow up of 6.7 years and adjusting for known prognostic factors, there was a significant increase in the risk of PSA failure (HR, 2.3 [95% CI, 1.1-4.5; p = 0.025) in men with eMRI-defined TV progression during nAST. Specifically, adjusted estimates of PSA failure were significantly higher (p = 0.032) in men with, compared with men without, eMRI-defined TV progression reaching 38% vs. 19%, respectively, by 5 years. Conclusion: Eradicating intraprostatic hormone refractory prostate cancer (HRPC) by maximizing local control and randomized trials assessing whether survival is improved when agents active against HRPC are combined with maximal local therapy are needed in men who progress based on eMRI during nAST

Localized Scleroderma, Systemic Sclerosis and Cardiovascular Risk: A Danish Nationwide Cohort Study.

Science.gov (United States)

Hesselvig, Jeanette Halskou; Kofoed, Kristian; Wu, Jashin J; Dreyer, Lene; Gislason, Gunnar; Ahlehoff, Ole

2018-03-13

Recent findings indicate that patients with systemic sclerosis have an increased risk of cardiovascular disease. To determine whether patients with systemic sclerosis or localized scleroderma are at increased risk of cardiovascular disease, a cohort study of the entire Danish population aged ≥ 18 and ≤ 100 years was conducted, followed from 1997 to 2011 by individual-level linkage of nationwide registries. Multivariable adjusted Cox regression models were used to estimate the hazard ratios (HRs) for a composite cardiovascular disease endpoint. A total of 697 patients with localized scleroderma and 1,962 patients with systemic sclerosis were identified and compared with 5,428,380 people in the reference population. In systemic sclerosis, the adjusted HR was 2.22 (95% confidence interval 1.99-2.48). No association was seen between patients with localized scleroderma and cardiovascular disease. In conclusion, systemic sclerosis is a significant cardiovascular disease risk factor, while patients with localized scleroderma are not at increased risk of cardiovascular disease.

Long-term survival of bladder preservation therapy with radiation and chemotherapy for locally invasive bladder cancer

International Nuclear Information System (INIS)

Noguchi, Sumio; Takase, Kazunori; Kubota, Yoshinobu; Masuda, Mitsunobu; Yao, Masahiro; Hosaka, Masahiko

1998-01-01

The prognoses and prognostic factors of the 54 patients with locally invasive bladder cancer who underwent bladder preservation therapy at Yokohama City University Hospital between 1977 and 1995 were analyzed statistically. The therapeutic modalities of bladder preservation were mainly radiation or chemotherapy. The prognosis for the patients who underwent bladder preservation therapy was worse than that for the patients who underwent total cystectomy. The prognostic factors of these patients were size and grade of tumor, presence of hydronephrosis and performance status (PS) of the patients by univariate analysis. Tumor grade was the most predictable prognostic factor using multivariate analysis. Only 17 patients survived more than 5 years after treatment; 78% of the survivors had good PS (0 or 1). Five of them died of cancer and two patients were alive with cancer. All of them had G3 tumors. These results suggest that patients with locally invasive G2 tumor could be candiates for bladder preservation therapy and patients who underwent bladder preservation therapy should be evaluated at 10 years post-therapy. (author)

Patterns of failure following bone marrow transplantation for metastatic breast cancer: the role of consolidative local therapy

International Nuclear Information System (INIS)

Shah, Amit B.; Hartsell, William F.; Ghalie, Richard; Kaizer, Herbert

1995-01-01

Purpose: The purpose of this analysis is to evaluate the patterns of failure and the role of local therapy in conjunction with bone marrow transplantation (BMT) for metastatic or recurrent breast cancer. Methods and Materials: Between June 1986 and November 1991, 46 patients with hormone unresponsive metastatic or recurrent breast cancer underwent high dose chemotherapy (HDC) with hematopoietic stem cell support. The most commonly used preparative regimen consisted of thiotepa (750 mg/m 2 ), cisplatin (150 mg/m 2 ), and cyclophosphamide (120 mg/kg) followed by autologous BMT. Consolidative surgery or irradiation was considered in patients whose cancer responded to BMT and had localized sites of disease. Results: Six patients (13%) died of BMT-related complications. Of the remaining 40 patients, 22 were candidates for consolidative therapy, and 18 of those patients received consolidative irradiation (17 patients) or surgery (1 patient) to one or more sites. At median follow-up of 27 months (range, 20-78), 12 of 18 (67%) patients have continuous local control at the 22 consolidated sites (1 of 4 controlled at chest wall sites, 7 of 8 at regional nodal sites, 7 of 7 at localized bone sites, and 1 of 3 at lung/mediastinal sites). Toxicity of consolidative irradiation was mainly limited to myelosuppression in 6 of 17 patients. Two patients did not complete the consolidative local therapy, one because of hematologic toxicity and one because of rapid systemic tumor progression during treatment. Conclusion: In patients with localized areas of extravisceral metastases, consolidative irradiation is feasible with acceptable hematologic toxicity. Consolidative irradiation can result in continuous local control, especially in isolated bone metastases and in regional nodal sites; however, the advantage is less clear in patients undergoing consolidative irradiation for chest wall failures. Because distant visceral metastases still remain a major site of failure after this HDC

Phase 1 Trial of Neoadjuvant Radiation Therapy Before Prostatectomy for High-Risk Prostate Cancer

International Nuclear Information System (INIS)

Koontz, Bridget F.; Quaranta, Brian P.; Pura, John A.; Lee, W.R.; Vujaskovic, Zeljko; Gerber, Leah; Haake, Michael; Anscher, Mitchell S.; Robertson, Cary N.; Polascik, Thomas J.; Moul, Judd W.

2013-01-01

Purpose: To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer. Methods and Materials: Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes. Results: No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors. Conclusions: Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes

Phase 1 Trial of Neoadjuvant Radiation Therapy Before Prostatectomy for High-Risk Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Koontz, Bridget F., E-mail: Bridget.Koontz@duke.edu [Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina (United States); Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina (United States); Quaranta, Brian P. [21st Century Oncology, Asheville, North Carolina (United States); Pura, John A. [Division of Biostatistics, Duke Cancer Institute, Durham, North Carolina (United States); Lee, W.R.; Vujaskovic, Zeljko [Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina (United States); Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina (United States); Gerber, Leah [Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina (United States); Haake, Michael [Southeast Radiation Oncology, Charlotte, North Carolina (United States); Anscher, Mitchell S. [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Robertson, Cary N.; Polascik, Thomas J.; Moul, Judd W. [Department of Surgery, Duke Cancer Institute, Durham, North Carolina (United States); Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina (United States)

2013-09-01

Purpose: To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer. Methods and Materials: Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes. Results: No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors. Conclusions: Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes.

Photodynamic therapy as a local therapeutic adjunct for the treatment of vertebral metastases

Science.gov (United States)

Yee, Albert; Burch, Shane; Akens, Margarete; Won, Emily; Lo, Victor; Wise-Milestone, Lisa; Bisland, Stuart; Theriault, Aimee; Niu, Carolyn; Wilson, Brian C.; Whyne, Cari

2013-03-01

Metastatic cancer causes the majority of tumors in bone, most frequently detected in the spinal column. Skeletal complications cause pain and neurologic impairment. Photodynamic therapy (PDT) has been used to treat a variety of cancers. Minimally invasive surgical (MIS) strategies may allow targeted light application essential for PDT within bone structures. The purpose of this manuscript is to provide an update on pre-clinical status as well as early clinical experience of a Phase I clinical trial on vertebral PDT. A pre-clinical (rnu/rnu rat) vertebral metastasis model of osteolytic (MT-1 breast cancer) was optimized and used to evaluate the effect of vertebral PDT. PDT alone and in combination with other standard local (radiation therapy, RT) and systemic (bisphosphonates, BP) therapies was evaluated through bioluminescence imaging, micro-CT based stereology, histology, and biomechanical testing. Single PDT treatment (photosensitizer BPD-MA, 690nm light) ablated tumor tissue in targeted vertebrae. PDT led to significant increases in bone structural properties, with greatest benefits observed from combined BP+PDT therapy: 76% and 19% increases in bone volume fraction in treated tumor-bearing and healthy untreated controls, respectively. Similar synergistic improvements (but of lesser magnitude) were found in combined PDT+RT treatments. The safety and feasibility of MIS+PDT were evaluated in scale-up animal studies, refining surgical technique for clinical translation. Following appropriate institutional review board as well as Health Canada approval, 5 patients (light only control group) have undergone protocoled treatment to date. These patients have guided further refinement of human therapeutic application from a laser delivery and vertebral bone access perspective.

Risk Perception and sexual risk behaviors among HIV-positive men on antiretroviral therapy.

Science.gov (United States)

Remien, Robert H; Halkitis, Perry N; O'Leary, Ann; Wolitski, Richard J; Gómez, Cynthia A

2005-06-01

There are reports of increased sexual risk behavior among people on highly active antiretroviral therapy (HAART) due to beliefs about risk of HIV transmission when on HAART. In a cross-sectional study (Seropositive Urban Men's Study), we examined the relationship between risk perception and sexual risk behavior among sexually active, culturally diverse HIV positive men who have sex with men (N = 456). Less than twenty-five percent engaged in unprotected anal sex (either with an HIV negative, or unknown-status partner, or an HIV positive partner) within the past 3 months. Most men believed there was significant health risk (to partner or self) associated with unprotected sex when on HAART. There was no increased risk behavior associated with being on HAART, although the perception of negative health consequences, including HIV transmission, when on HAART was significantly lower for the relatively small subset of men who reported unprotected sex. Prevention strategies need to be tailored to address risk perception associated with HAART.

Estimating Longitudinal Risks and Benefits From Cardiovascular Preventive Therapies Among Medicare Patients: The Million Hearts Longitudinal ASCVD Risk Assessment Tool: A Special Report From the American Heart Association and American College of Cardiology.

Science.gov (United States)

Lloyd-Jones, Donald M; Huffman, Mark D; Karmali, Kunal N; Sanghavi, Darshak M; Wright, Janet S; Pelser, Colleen; Gulati, Martha; Masoudi, Frederick A; Goff, David C

2017-03-28

The Million Hearts Initiative has a goal of preventing 1 million heart attacks and strokes-the leading causes of mortality-through several public health and healthcare strategies by 2017. The American Heart Association and American College of Cardiology support the program. The Cardiovascular Risk Reduction Model was developed by Million Hearts and the Center for Medicare & Medicaid Services as a strategy to assess a value-based payment approach toward reduction in 10-year predicted risk of atherosclerotic cardiovascular disease (ASCVD) by implementing cardiovascular preventive strategies to manage the "ABCS" (aspirin therapy in appropriate patients, blood pressure control, cholesterol management, and smoking cessation). The purpose of this special report is to describe the development and intended use of the Million Hearts Longitudinal ASCVD Risk Assessment Tool. The Million Hearts Tool reinforces and builds on the "2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk" by allowing clinicians to estimate baseline and updated 10-year ASCVD risk estimates for primary prevention patients adhering to the appropriate ABCS over time, alone or in combination. The tool provides updated risk estimates based on evidence from high-quality systematic reviews and meta-analyses of the ABCS therapies. This novel approach to personalized estimation of benefits from risk-reducing therapies in primary prevention may help target therapies to those in whom they will provide the greatest benefit, and serves as the basis for a Center for Medicare & Medicaid Services program designed to evaluate the Million Hearts Cardiovascular Risk Reduction Model. Copyright © 2017 American Heart Association, Inc., and the American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Local ablation therapy with contrast-enhanced ultrasonography for hepatocellular carcinoma: a practical review

Directory of Open Access Journals (Sweden)

Tae Kyoung Kim

2015-10-01

Full Text Available A successful program for local ablation therapy for hepatocellular carcinoma (HCC requires extensive imaging support for diagnosis and localization of HCC, imaging guidance for the ablation procedures, and post-treatment monitoring. Contrast-enhanced ultrasonography (CEUS has several advantages over computed tomography/magnetic resonance imaging (CT/MRI, including real-time imaging capability, sensitive detection of arterial-phase hypervascularity and washout, no renal excretion, no ionizing radiation, repeatability, excellent patient compliance, and relatively low cost. CEUS is useful for image guidance for isoechoic lesions. While contrast-enhanced CT/MRI is the standard method for the diagnosis of HCC and post-ablation monitoring, CEUS is useful when CT/MRI findings are indeterminate or CT/MRI is contraindicated. This article provides a practical review of the role of CEUS in imaging algorithms for pre- and post-ablation therapy for HCC.

Evidence-based music therapy practice: an integral understanding.

Science.gov (United States)

Abrams, Brian

2010-01-01

The American Music Therapy Association has recently put into action a plan called its Research Strategic Priority, with one of its central purposes to advance the music therapy field through research promoting Evidence-Based Practice of music therapy. The extant literature on music therapy practice, theory, and research conveys a range of very different perspectives on what may count as the "evidence" upon which practice is based. There is therefore a need to conceptualize evidence-based music therapy practice in a multifaceted, yet coherent and balanced way. The purpose of this paper is to illustrate a framework based upon four distinct epistemological perspectives on evidence-based music therapy practice that together represent an integral understanding.

Integrative Therapies for Women with a High Risk Pregnancy During Antepartum Hospitalization.

Science.gov (United States)

Schlegel, Merry L; Whalen, Jeanne L; Williamsen, Pilar M

High-risk pregnancies that require lengthy hospitalization can cause anxiety and stress for pregnant women. Integrative medicine therapies may be beneficial for this population, but have not been widely studied. The purpose of this study was to evaluate potential effects of acupuncture, guided imagery, Healing Touch, massage therapy, and reflexology on pain and anxiety of hospitalized pregnant women. A retrospective analysis of the effects of integrative medicine therapies was conducted; N = 554 individual therapies were provided to hospitalized women with high-risk pregnancies. They included acupuncture (n = 83), guided imagery (n = 71), Healing Touch (n = 119), massage therapy (n = 196), and reflexology (n = 85) over an 18-month period. Pain and anxiety were measured pre- and posttherapy using a scale of 0 to 10, where 0 means no pain or no anxiety and 10 means high pain or high anxiety. Analysis of mean scores of pre- and posttherapies for pain and anxiety found a decrease of pain and anxiety after all of the therapies, ranging from an 84.5% to 61.4% decrease for pain (p < .0001) and a 91% to 70. 9% decrease for anxiety (p < .0001). Overall, patients rated their anxiety higher than pain prior to each therapy. Hospitalized pregnant women responded favorably to the therapies. There were no adverse reactions reported. Results suggest potential benefits of integrative medicine therapies for this group of inpatients. Anxiety was more prevalent than pain among hospitalized pregnant women who received integrative medicine therapy.

Local therapy in localized Ewing tumors: results of 1058 patients treated in the CESS 81, CESS 86, and EICESS 92 trials

International Nuclear Information System (INIS)

Schuck, Andreas; Ahrens, Susanne; Paulussen, Michael; Kuhlen, Michaela; Koenemann, Stefan; Ruebe, Christian; Winkelmann, Winfried; Kotz, Rainer; Dunst, Juergen; Willich, Normann; Juergens, Heribert

2003-01-01

Purpose: The impact of different local therapy approaches on local control, event-free survival, and secondary malignancies in the CESS 81, CESS 86, and EICESS 92 trials was investigated. Methods and Materials: The data of 1058 patients with localized Ewing tumors were analyzed. Wherever feasible, a surgical local therapy approach was used. In patients with a poor histologic response or with intralesional and marginal resections, this was to be followed by radiotherapy (RT). In EICESS 92, preoperative RT was introduced for patients with expected close resection margins. Definitive RT was used in cases in which surgical resection seemed impossible. In CESS 81, vincristine, adriamycin, cyclophosphamide, and actinomycin D was used. In CESS 86, vincristine, adriamycin, ifosfamide, and actinomycin D was introduced for patients with central tumors or primaries >100 cm 3 . In CESS 92, etoposide, vincristine, adriamycin, ifosfamide, and actinomycin D was randomized against vincristine, adriamycin, ifosfamide, and actinomycin D in patients with primaries >100 cm 3 . Results: The rate of local failure was 7.5% after surgery with or without postoperative RT, and was 5.3% after preoperative and 26.3% after definitive RT (p=0.001). Event-free survival was reduced after definitive RT (p=0.0001). Irradiated patients represented a negatively selected population with unfavorable tumor sites. Definitive RT showed comparable local control to that of postoperative RT after intralesional resections. Patients with postoperative RT had improved local control after intralesional resections and in tumors with wide resection and poor histologic response compared with patients receiving surgery alone. Patients with marginal resections with or without postoperative radiotherapy showed comparable local control, yet the number of patients with good histologic response was higher in the latter treatment group (72.2% vs. 38.5%). Conclusion: Patients with resectable tumors after initial

Replacing SUs with incretin-based therapies for type 2 diabetes mellitus

DEFF Research Database (Denmark)

Knop, Filip K; Holst, Jens Juul; Vilsbøll, Tina

2008-01-01

Type 2 diabetes mellitus (T2DM) is a progressive disease characterized by insulin resistance, a steady decline in glucose-induced insulin secretion (most likely caused by a progressive decrease in functional beta-cell mass), and inappropriately regulated glucagon secretion; in combination...... are glucose-dependent, reducing the risk of hypoglycemia. GLP-1 inhibits glucagon secretion and decreases gastrointestinal motility, in turn reducing food intake and body weight. This feature review focuses on the challenges and feasibilities of replacing SU with incretin-based therapy in patients with T2DM....... - glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). More importantly, incretin-based therapies potentiate glucose-stimulated insulin secretion and may restore reduced glucose-induced insulin secretion in T2DM. Furthermore, the insulinotropic effects of GLP-1 and GIP...

Classifying PML risk with disease modifying therapies.

Science.gov (United States)

Berger, Joseph R

2017-02-01

To catalogue the risk of PML with the currently available disease modifying therapies (DMTs) for multiple sclerosis (MS). All DMTs perturb the immune system in some fashion. Natalizumab, a highly effective DMT, has been associated with a significant risk of PML. Fingolimod and dimethyl fumarate have also been unquestionably associated with a risk of PML in the MS population. Concerns about PML risk with other DMTs have arisen due to their mechanism of action and pharmacological parallel to other agents with known PML risk. A method of contextualizing PML risk for DMTs is warranted. Classification of PML risk was predicated on three criteria:: 1) whether the underlying condition being treated predisposes to PML in the absence of the drug; 2) the latency from initiation of the drug to the development of PML; and 3) the frequency with which PML is observed. Among the DMTs, natalizumab occupies a place of its own with respect to PML risk. Significantly lesser degrees of risk exist for fingolimod and dimethyl fumarate. Whether PML will be observed with other DMTs in use for MS, such as, rituximab, teriflunomide, and alemtuzumab, remains uncertain. A logical classification for stratifying DMT PML risk is important for both the physician and patient in contextualizing risk/benefit ratios. As additional experience accumulates regarding PML and the DMTs, this early effort will undoubtedly require revisiting. Copyright © 2016 Elsevier B.V. All rights reserved.

The radio-iodine therapy of the functional autonomy. Indications, findings, risks

International Nuclear Information System (INIS)

Reiners, C.

1990-01-01

The functional autonomy of the thyroid is a disorder, which appears in connection with iodine deficit and befalls the complete organ. An absolute indication for a radio-iodine-therapy is given in case of hyperthyreoidism (these are 25 % of all at the functional autonomy). Contrary to the operation method the advantage of the I-131-therapy is, that all of the functional autonome-cells can be reached. The risk at the I-131-therapy is low. (Botek)

Prostate-Specific Antigen Halving Time While on Neoadjuvant Androgen Deprivation Therapy Is Associated With Biochemical Control in Men Treated With Radiation Therapy for Localized Prostate Cancer

International Nuclear Information System (INIS)

Malik, Renuka; Jani, Ashesh B.; Liauw, Stanley L.

2011-01-01

Purpose: To assess whether the PSA response to neoadjuvant androgen deprivation therapy (ADT) is associated with biochemical control in men treated with radiation therapy (RT) for prostate cancer. Methods and Materials: In a cohort of men treated with curative-intent RT for localized prostate cancer between 1988 and 2005, 117 men had PSA values after the first and second months of neoadjuvant ADT. Most men had intermediate-risk (45%) or high-risk (44%) disease. PSA halving time (PSAHT) was calculated by first order kinetics. Median RT dose was 76 Gy and median total duration of ADT was 4 months. Freedom from biochemical failure (FFBF, nadir + 2 definition) was analyzed by PSAHT and absolute PSA nadir before the start of RT. Results: Median follow-up was 45 months. Four-year FFBF was 89%. Median PSAHT was 2 weeks. A faster PSA decline (PSAHT ≤2 weeks) was associated with greater FFBF (96% vs. 81% for a PSAHT >2 weeks, p = 0.0110). Those within the fastest quartile of PSAHTs (≤ 10 days) achieved a FFBF of 100%. Among high-risk patients, a PSAHT ≤2 weeks achieved a 4-yr FFBF of 93% vs. 70% for those with PSAHT >2 weeks (p = 0.0508). Absolute PSA nadir was not associated with FFBF. On multivariable analysis, PSAHT (p = 0.0093) and Gleason score (p = 0.0320) were associated with FFBF, whereas T-stage (p = 0.7363) and initial PSA level (p = 0.9614) were not. Conclusions: For men treated with combined ADT and RT, PSA response to the first month of ADT may be a useful criterion for prognosis and treatment modification.

Hormone therapy and cardiovascular risk markers and disease

DEFF Research Database (Denmark)

Pedersen, Susan H; Lokkegaard, Ellen; Ottesen, Bent

2006-01-01

therapy (HT), although an underlying healthy-user effect may account for these observations. Progestagens are added to protect against an increased risk of endometrial cancer observed with unopposed estrogen treatment. The inclusion of progestagen in HT has been associated with possible adverse......Biological studies have demonstrated estrogen's beneficial effect on cardiovascular risk factors, including plasma lipoproteins, atherogenesis, vascular reactivity, inflammation and antioxidative activity. Additionally, observational studies have supported a cardioprotective effect of hormone...... cardiovascular outcomes. Recent, large-scale, randomized clinical studies did not confirm a beneficial cardiovascular effect of HT. On the contrary, an increased risk was found with continuous combined estrogen-progestagen regimens. The progestagen used in these trials was medroxyprogesterone acetate and other...

First Evaluation of a Contingency Management Intervention Addressing Adolescent Substance Use and Sexual Risk Behaviors: Risk Reduction Therapy for Adolescents.

Science.gov (United States)

Letourneau, Elizabeth J; McCart, Michael R; Sheidow, Ashli J; Mauro, Pia M

2017-01-01

There is a need for interventions that comprehensively address youth substance use disorders (SUD) and sexual risk behaviors. Risk Reduction Therapy for Adolescents (RRTA) adapts a validated family-focused intervention for youth SUD to include sexual risk reduction components in a single intervention. In this first evaluation of RRTA, drug court involved youth were randomly assigned to RRTA (N=45) or usual services (US; N=60) and followed through 12-months post-baseline. RRTA included weekly cognitive behavior therapy and behavior management training and contingency-contracting with a point earning system managed by caregivers targeting drug use and sexual risk antecedents. Longitudinal models estimated within-group change and between-group differences through 6- and 12-month follow-up on outcomes for substance use, sexual risk behaviors, and protective HIV behaviors. Robust effects of the intervention were not detected under conditions of the study that included potent background interventions by the juvenile drug court. Considerations about future development and testing of sexual risk reduction therapy for youth are discussed, including the potential role of contingency management in future interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

Substrate mediated enzyme prodrug therapy

DEFF Research Database (Denmark)

Fejerskov, Betina; Jarlstad Olesen, Morten T; Zelikin, Alexander N

2017-01-01

Substrate mediated enzyme prodrug therapy (SMEPT) is a biomedical platform developed to perform a localized synthesis of drugs mediated by implantable biomaterials. This approach combines the benefits and at the same time offers to overcome the drawbacks for traditional pill-based drug administra......Substrate mediated enzyme prodrug therapy (SMEPT) is a biomedical platform developed to perform a localized synthesis of drugs mediated by implantable biomaterials. This approach combines the benefits and at the same time offers to overcome the drawbacks for traditional pill-based drug...

Cardiovascular Risk Following Fertility Therapy: Systematic Review and Meta-Analysis.

Science.gov (United States)

Dayan, Natalie; Filion, Kristian B; Okano, Marisa; Kilmartin, Caitlin; Reinblatt, Shauna; Landry, Tara; Basso, Olga; Udell, Jacob A

2017-09-05

The longer term cardiovascular effects of fertility therapy are unknown. The aim of this study was to summarize data linking fertility therapy with subsequent cardiovascular outcomes. We systematically searched published reports for studies addressing the question "does fertility therapy increase the risk of longer term cardiovascular outcomes?" We included: 1) human studies; 2) case control, cohort, or randomized designs with 3) exposure to fertility therapy and 4) cardiovascular outcomes clearly reported; 5) presence of comparison group; 6) minimum 1-year follow-up; and 7) adjustment for age. Two independent reviewers screened abstracts, titles, and full texts, and assessed study quality. We used the DerSimonian and Laird random-effects models to pool hazard ratios (HRs) with 95% confidence intervals (CIs) of the following outcomes: acute cardiac event; stroke; venous thromboembolism; hypertension; and diabetes mellitus, comparing women who received fertility therapy with those who did not. Six observational studies met inclusion criteria including 41,910 women who received fertility therapy and 1,400,202 women who did not. There was no increased risk of a cardiac event (pooled HR: 0.91; 95% CI: 0.67 to 1.25; I 2  = 36.6%), or diabetes mellitus (pooled HR: 0.93; 95% CI: 0.87 to 1.001; I 2  = 0%). Results were not pooled for hypertension (I 2  = 95.0%) and venous thromboembolism (I 2  = 82.3%). There was a trend toward higher risk of stroke (pooled HR: 1.25; 95% CI: 0.96 to 1.63; I 2  = 0%). The small number of studies and significant heterogeneity precludes definitive reassurance about the longer term cardiovascular safety of these treatments, particularly stroke. Future studies are needed to address ongoing knowledge gaps in this area. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Multiple Sclerosis: associated cardiometabolic risks and impact of exercise therapy

OpenAIRE

Jacobs, Jasper

2016-01-01

Multiple sclerosis (MS) is characterized by complex heterogeneous symptoms, which often leads to a more sedentary lifestyle. This lifestyle increases the likelihood to develop secondary health problems, like cardiometabolic risk (CMR) profile. However, in other population these secondary health problems can be, partly, reversed by exercise therapy. We hypothesized that MS affects the CMR profile, but the outcome can be reversed following exercise therapy. Persons with MS and matched healthy c...

[Drug susceptibility test guided therapy and novel empirical quadruple therapy for Helicobacter pylori infection: a network Meta-analysis].

Science.gov (United States)

Gou, Q Y; Yu, R B; Shi, R H

2017-05-10

Objective: To compare the efficacy and the risk of adverse effect of drug susceptibility test guided therapy and novel empirical quadruple therapy for Helicobacter ( H .) pylori infection. Methods: Literature retrieval was conducted by using major databases. Related papers published up to June 2015 were considered eligible if they were randomized control trials comparing different pharmacological formulations for H. pylori infection and used in a network Meta-analysis and a single rate Meta-analysis to evaluate the relative and absolute rates of H. pylori eradication and the risk of adverse effect. The Jadad score was used to evaluate the methodological quality. Funnel plot was constructed to evaluate the risk of publication bias. Begg's rank correlation test or Egger's regression intercept test was done for the asymmetry of funnel plot. Results: Twenty randomized control trials for the treatment of 6 753 initial treated patients with H. pylori infection were included. Drug susceptibility test guided therapy was significantly superior to concomitant therapy, hybrid therapy, sequential therapy and bismuth quadruple therapy. The culture-based therapy had the highest likelihood of improving clinical efficacy, with lowest risk of adverse effect. Concomitant therapy had the highest probability of causing adverse effect despite its effectiveness. Hybrid therapy and bismuth quadruple therapy were associated with lower risk of adverse effect and higher effectiveness. Conclusion: Drug susceptibility test guided therapy showed superiority to other 4 interventions for H. pylori eradication mentioned above. Hybrid therapy and bismuth quadruple therapy might be applied in the settings where the culture-based strategy is not available.

Local stakeholders' perception of landslide and flood risks in Iasi County, Romania

Science.gov (United States)

Ciprian Margarint, Mihai; Niculita, Mihai; Rosu, Lucian

2015-04-01

Risk perception is an important issue for an efficient management and mitigation measures of natural hazards and theirs negative consequences on social and economic activity. At administrative unit scale (LAU2), local stakeholders play an effective role in case of an emergency situation, regarding the warning and alerting the population, collaboration with specialized institution and managing material assistance during and after the crisis. In addition they are among the best connoisseurs of local community and places, and consequently they could substantial help the national level forces during emergency situations. These issues argues the high degree of responsibilities assigned to Romanian mayors, and is reflected in the legislation in terms of evaluation of damages produced and the management of natural hazards, like landslide and floods. Also their degree of awareness can assess more accurately the collective perception against the individual one. In this work we have assessed the local stakeholders' perception for natural risks in general, and particularly for landslides and floods. We have tested the discrepancies of the specific risks perception and an assessment of correspondence between scientific outputs versus the subjective judgement the administrative decision makers. This approach was based on a questionnaire which was applied in the summer of 2014, to all 98 mayors from Iasi County, north-east Romania. It contained 12 questions structured in a specific mode, from general to particular. The assessment of the answers provided from the commune halls, was realized with integration in a GIS environment of codes assigned to each question, and the overlay with the scientific outputs regarding landslide occurrence and susceptibility and floods risk maps. The differences between the outputs of the questionnaires and the scientific outputs of landslide and flood risk was further analyzed and interpreted. There were registered large variations of answers and

Locally advanced prostate cancer: a population-based study of treatment patterns.

Science.gov (United States)

Lowrance, William T; Elkin, Elena B; Yee, David S; Feifer, Andrew; Ehdaie, Behfar; Jacks, Lindsay M; Atoria, Coral L; Zelefsky, Michael J; Scher, Howard I; Scardino, Peter T; Eastham, James A

2012-05-01

Study Type--Therapy (practice patterns). Level of Evidence 2b. What's known on the subject? And what does the study add? The treatment of locally advanced prostate cancer varies widely even though there is level one evidence supporting the use of multimodality therapy as compared with monotherapy. This study defines treatment patterns of locally advanced prostate cancer within the United States and identifies predicators of who receives multimodality therapy rather than monotherapy. • To identify treatment patterns and predictors of receiving multimodality therapy in patients with locally advanced prostate cancer (LAPC). • The cohort comprised patients ≥66 years with clinical stage T3 or T4 non-metastatic prostate cancer diagnosed between 1998 and 2005 identified from the Surveillance, Epidemiology and End Results (SEER) cancer registry records linked with Medicare claims. • Treatments were classified as radical prostatectomy (RP), radiation therapy (RT) and androgen deprivation therapy (ADT) received within 6 and 24 months of diagnosis. • We assessed trends over time and used multivariable logistic regression to identify predictors of multimodality treatment. • Within the first 6 months of diagnosis, 1060 of 3095 patients (34%) were treated with a combination of RT and ADT, 1486 (48%) received monotherapy (RT alone, ADT alone or RP alone), and 461 (15%) received no active treatment. • The proportion of patients who received RP increased, exceeding 10% in 2005. • Use of combined RT and ADT and use of ADT alone fluctuated throughout the study period. • In all 6% of patients received RT alone in 2005. • Multimodality therapy was less common in patients who were older, African American, unmarried, who lived in the south, and who had co-morbidities or stage T4 disease. • Treatment of LAPC varies widely, and treatment patterns shifted during the study period. • The slightly increased use of multimodality therapy since 2003 is encouraging, but

A performance-oriented and risk-based regulation for containment testing

International Nuclear Information System (INIS)

Dey, M.

1994-01-01

In August 1992, the NRC initiated a major initiative to develop requirements for containment testing that are less prescriptive, and more performance-oriented and risk-based. This action was a result of public comments and several studies that concluded that the economic burden of certain, present containment testing requirements are not commensurate with their safety benefits. The rulemaking will include consideration of relaxing the allowable containment leakage rate, increasing the interval for the integrated containment test, and establishing intervals for the local containment leak rate tests based on their performance. A study has been conducted to provide technical information for establishing the performance criteria for containment tests, the allowable leakage rate, commensurate with its significance to total public risk. The study used results of a recent comprehensive study conducted by the NRC, NUREG-1150, 'Severe Accident Risks: An Assessment for Five U.S. Nuclear Power Plants,' to examine the sensitivity of containment leakage to public risk. Risk was found to be insensitive to containment leakage rate up to levels of about 100 percent-volume per day for certain types of containments. PRA methods have also been developed to establish risk-based intervals for containment tests based on their past experience. Preliminary evaluations show that increasing the interval for the integrated containment leakage test from three times to once every ten years would have an insignificant impact on public risk. Preliminary analyses of operational experience data for local leak rate tests show that performance-based testing, valves and penetrations that perform well are tested less frequently, is feasible with marginal impact on safety. The above technical studies are being used to develop efficient (cost-effective) requirements for containment tests. (author). 4 refs., 2 figs

Feasibility of combined modality therapy for localized high-grade soft tissue sarcomas in adults

International Nuclear Information System (INIS)

Blum, R.H.; Greenberger, J.S.; Wilson, R.E.; Corson, J.M.

1979-01-01

Seventeen consecutive patients with localized, high grade soft tissue sarcomas had resection of their primary tumor, radiation therapy and chemotherapy. The soft tissue sarcoma was primary in 14 patients and regionally recurrent in 3 patients. Chemotherapy consisted of cyclophosphamide 500 mg/M 2 day 1, Adriamycin (ADR) 60 mg/M 2 day 2, and DTIC 400 mg/M 2 days 1 and 2, given every 21 days to a maximum ADR dose of 450 mg/M 2 . Cyclophosphamide and DTIC were then given to a total duration of 1 year. Radiation therapy consisted of 4000 to 5000 rad by megavoltage photons in 5 weeks, and in selected cases, an additional 1500 to 2000 rad by electron beam boost in the tumor bed delivered over 2 additional weeks. Following surgery, 12 patients were treated sequentially with an interval of chemotherapy, radiation therapy and then the completion of chemotherapy. The added morbidity of this sequential approach is minimal: one patient of 12 had delayed primary healing of her wound, 1 of 10 patients required a break in radiation therapy because of skin erythema. Four patients were treated with intensive pre-chemotherapy radiation therapy because of inadequate surgical margins. The median time on study was 18 months from onset of treatment (range, 8 to 41 months). Although there have been no local, regional or distant recurrences, the follow-up time is inadequate to assess the therapeutic benefit of this combined modality treatment

Chitosan in Mucoadhesive Drug Delivery: Focus on Local Vaginal Therapy

Directory of Open Access Journals (Sweden)

Toril Andersen

2015-01-01

Full Text Available Mucoadhesive drug therapy destined for localized drug treatment is gaining increasing importance in today’s drug development. Chitosan, due to its known biodegradability, bioadhesiveness and excellent safety profile offers means to improve mucosal drug therapy. We have used chitosan as mucoadhesive polymer to develop liposomes able to ensure prolonged residence time at vaginal site. Two types of mucoadhesive liposomes, namely the chitosan-coated liposomes and chitosan-containing liposomes, where chitosan is both embedded and surface-available, were made of soy phosphatidylcholine with entrapped fluorescence markers of two molecular weights, FITC-dextran 4000 and 20,000, respectively. Both liposomal types were characterized for their size distribution, zeta potential, entrapment efficiency and the in vitro release profile, and compared to plain liposomes. The proof of chitosan being both surface-available as well as embedded into the liposomes in the chitosan-containing liposomes was found. The capability of the surface-available chitosan to interact with the model porcine mucin was confirmed for both chitosan-containing and chitosan-coated liposomes implying potential mucoadhesive behavior. Chitosan-containing liposomes were shown to be superior in respect to the simplicity of preparation, FITC-dextran load, mucoadhesiveness and in vitro release and are expected to ensure prolonged residence time on the vaginal mucosa providing localized sustained release of entrapped model substances.

INTRAOPERATIVE PHOTODYNAMIC THERAPY FOR METASTATIC PERITONEAL TUMORS

Directory of Open Access Journals (Sweden)

E. A. Suleimanov

2016-01-01

Full Text Available This review is devoted to the cytoreductive treatment of malignant tumors of the abdominal organs. The actuality of the issue is determined both by increase of the incidence of abdominal cancer in Russia and in majority of developed countries and by high rate diagnosis on late stages of disease. The methods of treatment of peritoneal carcinomatosis, based on possible effects on the secondary peritoneal tumors after surgical cytoreduction to reduce the risk of local recurrence and disease progression are described. These methods of additional intraoperative specific antitumor action include intraoperative radiation therapy, hyperthermic intraperitoneal chemotherapy, intraoperative photodynamic therapy characterized by differences in difficulty of performance, mechanisms of effect on tumor and healthy tissues, efficiency. Benefits, opportunities and possibilities of application of intraoperative photodynamic therapy (IOPDT for secondary peritoneal tumors are described in details, the results of a number of domestic and foreign clinical studies are shown, the successful application of intraoperative photodynamic therapy in clinical oncology, which allows reducing the risk of secondary tumor lesions of the peritoneum significantly, is demonstrated. Photodynamic therapy – a method with high efficiency and almost no side effects and complications, based on the ability of photosensitizer to accumulate selectively and retain in the high proliferative tissues. The advantages of this type of treatment of patients with peritoneal carcinomatosis are a selective effect on the peritoneal carcinomatosis and on visually detected tumor tissue, high efficiency in patients with malignant tumors of the abdominal cavity and pelvis combined with surgical cytoreduction, minimal effect on normal organs and tissues of the patient, well tolerated procedure.

A comparison of laparoscopic and open surgery following pre-operative chemoradiation therapy for locally advanced lower rectal cancer

International Nuclear Information System (INIS)

Kusano, Toru; Inomata, Masafumi; Hiratsuka, Takahiro

2014-01-01

Although pre-operative chemoradiation therapy for advanced lower rectal cancer is a controversial treatment modality, it is increasingly used in combination with surgery. Few studies have considered the combination of chemoradiation therapy followed by laparoscopic surgery for locally advanced lower rectal cancer; therefore, this study aimed to assess the usefulness of this therapeutic combination. We retrospectively reviewed the medical records of patients with locally advanced lower rectal cancer treated by pre-operative chemoradiation therapy and surgery from February 2002 to November 2012 at Oita University. We divided patients into an open surgery group and a laparoscopic surgery group and evaluated various parameters by univariate and multivariate analyses. In total, 33 patients were enrolled (open surgery group, n=14; laparoscopic surgery group, n=19). Univariate analysis revealed that compared with the open surgery group, operative time was significantly longer, whereas intra-operative blood loss and intra-operative blood transfusion requirements were significantly less in the laparoscopic surgery group. There were no significant differences in post-operative complication and recurrence rates between the two groups. According to multivariate analysis, operative time and intra-operative blood loss were significant predictors of outcome in the laparoscopic surgery group. This study suggests that laparoscopic surgery after chemoradiation therapy for locally advanced lower rectal cancer is a safe procedure. Further prospective investigation of the long-term oncological outcomes of laparoscopic surgery after chemoradiation therapy for locally advanced lower rectal cancer is required to confirm the advantages of laparoscopic surgery over open surgery. (author)

Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials.

Science.gov (United States)

Mega, J L; Stitziel, N O; Smith, J G; Chasman, D I; Caulfield, M; Devlin, J J; Nordio, F; Hyde, C; Cannon, C P; Sacks, F; Poulter, N; Sever, P; Ridker, P M; Braunwald, E; Melander, O; Kathiresan, S; Sabatine, M S

2015-06-06

Genetic variants have been associated with the risk of coronary heart disease. In this study, we tested whether or not a composite of these variants could ascertain the risk of both incident and recurrent coronary heart disease events and identify those individuals who derive greater clinical benefit from statin therapy. A community-based cohort study (the Malmo Diet and Cancer Study) and four randomised controlled trials of both primary prevention (JUPITER and ASCOT) and secondary prevention (CARE and PROVE IT-TIMI 22) with statin therapy, comprising a total of 48,421 individuals and 3477 events, were included in these analyses. We studied the association of a genetic risk score based on 27 genetic variants with incident or recurrent coronary heart disease, adjusting for traditional clinical risk factors. We then investigated the relative and absolute risk reductions in coronary heart disease events with statin therapy stratified by genetic risk. We combined data from the different studies using a meta-analysis. When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient in risk for incident or recurrent coronary heart disease was shown. Compared with the low genetic risk category, the multivariable-adjusted hazard ratio for coronary heart disease for the intermediate genetic risk category was 1·34 (95% CI 1·22-1·47, pgenetic risk category was 1·72 (1·55-1·92, pgenetic risk categories. Similarly, we noted greater absolute risk reductions in those individuals in higher genetic risk categories (p=0·0101), resulting in a roughly threefold decrease in the number needed to treat to prevent one coronary heart disease event in the primary prevention trials. Specifically, in the primary prevention trials, the number needed to treat to prevent one such event in 10 years was 66 in people at low genetic risk, 42 in those at intermediate genetic risk, and 25 in those at high

Regional Lymph Node Uptake of [{sup 18}F]Fluorodeoxyglucose After Definitive Chemoradiation Therapy Predicts Local-Regional Failure of Locally Advanced Non-Small Cell Lung Cancer: Results of ACRIN 6668/RTOG 0235

Energy Technology Data Exchange (ETDEWEB)

Markovina, Stephanie [Mallinckrodt Institute of Radiology and Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri (United States); Duan, Fenghai [Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island (United States); Snyder, Bradley S. [Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island (United States); Siegel, Barry A. [Mallinckrodt Institute of Radiology and Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri (United States); Machtay, Mitchell [Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (United States); Bradley, Jeffrey D., E-mail: jbradley@radonc.wustl.edu [Mallinckrodt Institute of Radiology and Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri (United States)

2015-11-01

Purpose: The American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group (RTOG) 0235 study demonstrated that standardized uptake values (SUV) on post-treatment [{sup 18}F]fluorodeoxyglucose-positron emission tomography (FDG-PET) correlated with survival in locally advanced non-small cell lung cancer (NSCLC). This secondary analysis determined whether SUV of regional lymph nodes (RLNs) on post-treatment FDG-PET correlated with patient outcomes. Methods and Materials: Included for analysis were patients treated with concurrent chemoradiation therapy, using radiation doses ≥60 Gy, with identifiable FDG-avid RLNs (distinct from primary tumor) on pretreatment FDG-PET, and post-treatment FDG-PET data. ACRIN core laboratory SUV measurements were used. Event time was calculated from the date of post-treatment FDG-PET. Local-regional failure was defined as failure within the treated RT volume and reported by the treating institution. Statistical analyses included Wilcoxon signed rank test, Kaplan-Meier curves (log rank test), and Cox proportional hazards regression modeling. Results: Of 234 trial-eligible patients, 139 (59%) had uptake in both primary tumor and RLNs on pretreatment FDG-PET and had SUV data from post-treatment FDG-PET. Maximum SUV was greater for primary tumor than for RLNs before treatment (P<.001) but not different post-treatment (P=.320). Post-treatment SUV of RLNs was not associated with overall survival. However, elevated post-treatment SUV of RLNs, both the absolute value and the percentage of residual activity compared to the pretreatment SUV were associated with inferior local-regional control (P<.001). Conclusions: High residual metabolic activity in RLNs on post-treatment FDG-PET is associated with worse local-regional control. Based on these data, future trials evaluating a radiation therapy boost should consider inclusion of both primary tumor and FDG-avid RLNs in the boost volume to maximize local

Regional Lymph Node Uptake of ["1"8F]Fluorodeoxyglucose After Definitive Chemoradiation Therapy Predicts Local-Regional Failure of Locally Advanced Non-Small Cell Lung Cancer: Results of ACRIN 6668/RTOG 0235

International Nuclear Information System (INIS)

Markovina, Stephanie; Duan, Fenghai; Snyder, Bradley S.; Siegel, Barry A.; Machtay, Mitchell; Bradley, Jeffrey D.

2015-01-01

Purpose: The American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group (RTOG) 0235 study demonstrated that standardized uptake values (SUV) on post-treatment ["1"8F]fluorodeoxyglucose-positron emission tomography (FDG-PET) correlated with survival in locally advanced non-small cell lung cancer (NSCLC). This secondary analysis determined whether SUV of regional lymph nodes (RLNs) on post-treatment FDG-PET correlated with patient outcomes. Methods and Materials: Included for analysis were patients treated with concurrent chemoradiation therapy, using radiation doses ≥60 Gy, with identifiable FDG-avid RLNs (distinct from primary tumor) on pretreatment FDG-PET, and post-treatment FDG-PET data. ACRIN core laboratory SUV measurements were used. Event time was calculated from the date of post-treatment FDG-PET. Local-regional failure was defined as failure within the treated RT volume and reported by the treating institution. Statistical analyses included Wilcoxon signed rank test, Kaplan-Meier curves (log rank test), and Cox proportional hazards regression modeling. Results: Of 234 trial-eligible patients, 139 (59%) had uptake in both primary tumor and RLNs on pretreatment FDG-PET and had SUV data from post-treatment FDG-PET. Maximum SUV was greater for primary tumor than for RLNs before treatment (P<.001) but not different post-treatment (P=.320). Post-treatment SUV of RLNs was not associated with overall survival. However, elevated post-treatment SUV of RLNs, both the absolute value and the percentage of residual activity compared to the pretreatment SUV were associated with inferior local-regional control (P<.001). Conclusions: High residual metabolic activity in RLNs on post-treatment FDG-PET is associated with worse local-regional control. Based on these data, future trials evaluating a radiation therapy boost should consider inclusion of both primary tumor and FDG-avid RLNs in the boost volume to maximize local-regional control.

Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk

DEFF Research Database (Denmark)

Rudolph, Anja; Hein, Rebecca; Lindström, Sara

2013-01-01

Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in 11 case...

Office-based Management of Recurrent Respiratory Papilloma.

Science.gov (United States)

Motz, Kevin M; Hillel, Alexander T

2016-06-01

This review will highlight the indications and benefits of office-based therapy for recurrent respiratory papillomatosis (RRP) and discuss the utilization of photo-dynamic lasers and adjuvant medical therapy in office-based settings. Office-based management of RRP allows for more timely interventions, is preferred by the majority of patients, and negates the risk of general anesthesia. Current literature argues for the utilization of KTP laser over CO 2 laser for office-based treatment of RRP. Medical therapies for RRP are limited, but agents such as bevacizumab are promising and have been shown to reduce disease burden. Medical therapies that can induce disease remission are still needed. Office-based procedures save time and healthcare expenses compared to like procedures in the operating room. However, the increased frequency for office-based procedures predicts similar overall healthcare costs for office-based and OR laser excision of RRP. Office-based management of RRP is a feasible and well-tolerated strategy in appropriately selected patients with adequate local anesthesia.

Menopausal Estrogen Therapy Benefits and Risks Vary by Age, WHI Analysis Suggests

Science.gov (United States)

Long-term follow-up data from the Women’s Health Initiative (WHI) provide new information about the potential risks and benefits of hormone therapy to treat symptoms related to menopause, including its effect on breast cancer risk,

Risk-informed local action planning against flooding: lessons learnt and way forward for a case study in Spain

Directory of Open Access Journals (Sweden)

Castillo-Rodríguez J.T.

2016-01-01

Full Text Available After 29 years of the largest flood event in modern times (with the highest recorded rainfall rate at the Iberian Peninsula with 817 mm in 24 hours, the municipality of Oliva faces the challenge of mitigating flood risk through the development and implementation of a local action plan, in line with other existent and ongoing structural measures for flood risk reduction. Located 65 km from Valencia, on the South-Eastern coast of Spain, Oliva is affected by pluvial, river and coastal flooding and it is characterized by a complex and wide-ranging geography and high seasonal variation in population. A quantitative flood risk analysis has been performed to support the definition of flood risk management strategies. This paper shows how hazard, exposure and vulnerability analyses provide valuable information for the development of a local action plan against flooding, for example by identifying areas with highest societal and economic risk levels. It is concluded that flood risk management actions, such as flood warning and monitoring or evacuation, should not be applied homogenously at local scale, but instead actions should be adapted based on spatial clustering. Implications about the impact of education and training on flood risk reduction are also addressed and discusse

Mammographic, pathologic, and treatment-related factors associated with local recurrence in patients with early-stage breast cancer treated with breast conserving therapy

International Nuclear Information System (INIS)

Kini, Vijay R.; Vicini, Frank A.; Frazier, Robert; Victor, Sandra J.; Wimbish, Kathryn; Martinez, Alvaro A.

1999-01-01

Background: We retrospectively reviewed our institution's experience treating early-stage breast cancer patients with breast conserving therapy (BCT) to determine clinical, pathologic, mammographic, and treatment-related factors associated with outcome. Methods: Between January 1980 and December 1987, 400 cases of Stage I and II breast cancer were managed with BCT at William Beaumont Hospital, Royal Oak, Michigan. All patients underwent at least an excisional biopsy. Radiation treatment consisted of delivering 45-50 Gy to the whole breast, followed by a boost to the tumor bed to at least 60 Gy in all patients. The median follow-up in the 292 surviving patients is 118 months. Multiple clinical, pathologic, mammographic, and treatment-related factors were analyzed for an association with local recurrence and survival. Results: A total of 37 local recurrences developed in the treated breast, for a 5- and 10-year actuarial rate of 4% and 10%, respectively. On univariate analysis, patient age ≤ 35 years (25% vs. 7%, p = 0.004), and positive surgical margins (17% vs. 6%, p = 0.018) were associated with an increased risk of local recurrence at 10 years. On multivariate analysis, only age ≤ 35 years remained significant. A subset analysis of 214 patients with evaluable mammographic findings was performed. On univariate analysis, age ≤ 35 years (38% vs. 8%, p = 0.0029) and the presence of calcifications on preoperative mammography (22% vs. 6%, p = 0.0016) were associated with an increased risk of local recurrence. On multivariate analysis, both of these factors remained significant. The presence of calcifications on preoperative mammography did not affect the rates of overall survival, disease-free survival, and cause-specific survival. Conclusion: In patients with early-stage breast cancer treated with BCT, age ≤ 35 years and calcifications on preoperative mammography appear to be associated with an increased risk of local recurrence

Enhancing local action planning through quantitative flood risk analysis: a case study in Spain

Science.gov (United States)

Castillo-Rodríguez, Jesica Tamara; Escuder-Bueno, Ignacio; Perales-Momparler, Sara; Ramón Porta-Sancho, Juan

2016-07-01

This article presents a method to incorporate and promote quantitative risk analysis to support local action planning against flooding. The proposed approach aims to provide a framework for local flood risk analysis, combining hazard mapping with vulnerability data to quantify risk in terms of expected annual affected population, potential injuries, number of fatalities, and economic damages. Flood risk is estimated combining GIS data of loads, system response, and consequences and using event tree modelling for risk calculation. The study area is the city of Oliva, located on the eastern coast of Spain. Results from risk modelling have been used to inform local action planning and to assess the benefits of structural and non-structural risk reduction measures. Results show the potential impact on risk reduction of flood defences and improved warning communication schemes through local action planning: societal flood risk (in terms of annual expected affected population) would be reduced up to 51 % by combining both structural and non-structural measures. In addition, the effect of seasonal population variability is analysed (annual expected affected population ranges from 82 to 107 %, compared with the current situation, depending on occupancy rates in hotels and campsites). Results highlight the need for robust and standardized methods for urban flood risk analysis replicability at regional and national scale.

Mindfulness-based cognitive therapy for depression: trends and developments

Directory of Open Access Journals (Sweden)

MacKenzie MB

2016-05-01

Full Text Available Meagan B MacKenzie,1 Nancy L Kocovski21Department of Psychology, Ryerson University, Toronto, ON, Canada; 2Department of Psychology, Wilfrid Laurier University, Waterloo, ON, CanadaAbstract: Mindfulness-based cognitive therapy (MBCT was developed as a psychological intervention for individuals at risk of depressive relapse. Possible mechanisms of change for this intervention are in line with its theoretical underpinnings, and include increases in mindfulness and/or decreases in negative repetitive thoughts. This review provides an overview of current trends in MBCT research, including efficacy and questions regarding the specific effects of MBCT in light of recent comparisons with structurally equivalent control conditions, mechanisms of change, and moderators of treatment outcome. In addition, future directions are discussed, such as challenges with training an adequate number of therapists and disseminating this therapy.Keywords: MBCT, efficacy, mechanisms of change, dissemination, moderators

Starting Hormone Therapy at Menopause Increases Breast Cancer Risk

Science.gov (United States)

According to a January 28, 2011 article in the Journal of the National Cancer Institute, women who start taking menopausal hormone therapy around the time of menopause have a higher risk of breast cancer than women who begin taking hormones a few years later.

MicroRNA-based Therapy in Animal Models of Selected Gastrointestinal Cancers

Directory of Open Access Journals (Sweden)

Jana Merhautova

2016-09-01

Full Text Available Gastrointestinal cancer accounts for the 20 most frequent cancer diseases worldwide and there is a constant urge to bring new therapeutics with new mechanism of action into the clinical practice. Quantity of in vitro and in vivo evidences indicate, that exogenous change in pathologically imbalanced microRNAs (miRNAs is capable of transforming the cancer cell phenotype. This review analyzed preclinical miRNA-based therapy attempts in animal models of gastric, pancreatic, gallbladder, and colorectal cancer. From more than 400 original articles, 26 was found to assess the effect of miRNA mimics, precursors, expression vectors, or inhibitors administered locally or systemically being an approach with relatively high translational potential. We have focused on mapping available information on animal model used (animal strain, cell line, xenograft method, pharmacological aspects (oligonucleotide chemistry, delivery system, posology, route of administration and toxicology assessments. We also summarize findings in the field pharmacokinetics and toxicity of miRNA-based therapy.□

Risk group dependence of dose-response for biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer

International Nuclear Information System (INIS)

Levegruen, Sabine; Jackson, Andrew; Zelefsky, Michael J.; Venkatraman, Ennapadam S.; Skwarchuk, Mark W.; Schlegel, Wolfgang; Fuks, Zvi; Leibel, Steven A.; Ling, C. Clifton

2002-01-01

Background and purpose: We fit phenomenological tumor control probability (TCP) models to biopsy outcome after three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer patients to quantify the local dose-response of prostate cancer. Materials and methods: We analyzed the outcome after photon beam 3D-CRT of 103 patients with stage T1c-T3 prostate cancer treated at Memorial Sloan-Kettering Cancer Center (MSKCC) (prescribed target doses between 64.8 and 81 Gy) who had a prostate biopsy performed ≥2.5 years after end of treatment. A univariate logistic regression model based on D mean (mean dose in the planning target volume of each patient) was fit to the whole data set and separately to subgroups characterized by low and high values of tumor-related prognostic factors T-stage ( 6), and pre-treatment prostate-specific antigen (PSA) (≤10 ng/ml vs. >10 ng/ml). In addition, we evaluated five different classifications of the patients into three risk groups, based on all possible combinations of two or three prognostic factors, and fit bivariate logistic regression models with D mean and the risk group category to all patients. Dose-response curves were characterized by TCD 50 , the dose to control 50% of the tumors, and γ 50 , the normalized slope of the dose-response curve at TCD 50 . Results: D mean correlates significantly with biopsy outcome in all patient subgroups and larger values of TCD 50 are observed for patients with unfavorable compared to favorable prognostic factors. For example, TCD 50 for high T-stage patients is 7 Gy higher than for low T-stage patients. For all evaluated risk group definitions, D mean and the risk group category are independent predictors of biopsy outcome in bivariate analysis. The fit values of TCD 50 show a clear separation of 9-10.6 Gy between low and high risk patients. The corresponding dose-response curves are steeper (γ 50 =3.4-5.2) than those obtained when all patients are analyzed together (γ 50 =2

Spontaneous subdural hematoma and antiplatelet therapy: Does efficacy of Ticagrelor come with added risk?

Directory of Open Access Journals (Sweden)

Pattanagere Manjunatha Suryanarayana Sharma

2015-12-01

Full Text Available Antiplatelet therapy has established clinical benefit on cardiovascular outcome and has reduced the rates of re-infarction/in stent thrombosis following percutaneous coronary intervention in acute coronary syndromes. Major bleeding episodes can occur with antiplatelet therapy and intracranial hemorrhage (ICH is one of the most feared complications resulting in significant morbidity and mortality. Identification of high risk groups and judicious use of antiplatelet therapy reduces the bleeding risk. Ticagrelor is a newer P2Y12 receptor antagonist with established clinical benefit. However, risks of having an ICH with these newer molecules cannot be ignored. Here, we report a case of spontaneous acute subdural hematoma developing in a patient on antiplatelet therapy with aspirin and ticagrelor. Early recognition, discontinuation of the medication and appropriate management resulted in resolution of hematoma and good clinical outcome. Authors have reviewed the antithrombotic drugs and their tendencies in causing intracranial bleeds from a neurophysicians perspective.

Utilizing time-driven activity-based costing to understand the short- and long-term costs of treating localized, low-risk prostate cancer.

Science.gov (United States)

Laviana, Aaron A; Ilg, Annette M; Veruttipong, Darlene; Tan, Hung-Jui; Burke, Michael A; Niedzwiecki, Douglas R; Kupelian, Patrick A; King, Chris R; Steinberg, Michael L; Kundavaram, Chandan R; Kamrava, Mitchell; Kaplan, Alan L; Moriarity, Andrew K; Hsu, William; Margolis, Daniel J A; Hu, Jim C; Saigal, Christopher S

2016-02-01

Given the costs of delivering care for men with prostate cancer remain poorly described, this article reports the results of time-driven activity-based costing (TDABC) for competing treatments of low-risk prostate cancer. Process maps were developed for each phase of care from the initial urologic visit through 12 years of follow-up for robotic-assisted laparoscopic prostatectomy (RALP), cryotherapy, high-dose rate (HDR) and low-dose rate (LDR) brachytherapy, intensity-modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and active surveillance (AS). The last modality incorporated both traditional transrectal ultrasound (TRUS) biopsy and multiparametric-MRI/TRUS fusion biopsy. The costs of materials, equipment, personnel, and space were calculated per unit of time and based on the relative proportion of capacity used. TDABC for each treatment was defined as the sum of its resources. Substantial cost variation was observed at 5 years, with costs ranging from $7,298 for AS to $23,565 for IMRT, and they remained consistent through 12 years of follow-up. LDR brachytherapy ($8,978) was notably cheaper than HDR brachytherapy ($11,448), and SBRT ($11,665) was notably cheaper than IMRT, with the cost savings attributable to shorter procedure times and fewer visits required for treatment. Both equipment costs and an inpatient stay ($2,306) contributed to the high cost of RALP ($16,946). Cryotherapy ($11,215) was more costly than LDR brachytherapy, largely because of increased single-use equipment costs ($6,292 vs $1,921). AS reached cost equivalence with LDR brachytherapy after 7 years of follow-up. The use of TDABC is feasible for analyzing cancer services and provides insights into cost-reduction tactics in an era focused on emphasizing value. By detailing all steps from diagnosis and treatment through 12 years of follow-up for low-risk prostate cancer, this study has demonstrated significant cost variation between competing treatments. © 2015

Impact of attention deficit hyperactivity disorder therapy on fracture risk in children treated in German pediatric practices.

Science.gov (United States)

Jacob, L; Kostev, K

2017-04-01

Two thousand eight hundred ninety-four children and adolescents treated by 243 pediatricians were analyzed. Patients receiving attention deficit hyperactivity disorder (ADHD) medications were at a lower risk of fractures than patients without ADHD medications. The strongest impact was in the age group of 6-9 years. Finally, there was a significant association between therapy duration and fracture risk. The aim of this study was to analyze the impact of ADHD therapy on fracture risk in children treated by German pediatricians. Children and adolescents initially diagnosed with ADHD and fractures between 2010 and 2015 were identified by 243 pediatricians. In this nested case-control study, each ADHD case with a fracture was matched (1:1) to an ADHD control without a fracture for age, gender, index year, and physician. In total, 2894 individuals were available for analysis. The main outcome of the study was the risk of fracture as a function of ADHD therapy. Multivariate logistic regression models were created to determine the effect of ADHD therapy on the risk of fracture in the entire population and in three age-specific subgroups. Patients receiving ADHD medications were at a lower risk of fracture than patients without ADHD medications (OR = 0.61). The impact of ADHD therapy on the risk of fracture was stronger in the age group of 6-9 years (OR = 0.41) than in the age groups of 10-13 years (OR = 0.68) and 14-17 years (OR = 0.74). Finally, a significant correlation was found between therapy duration and fracture risk (OR = 0.71 per month). ADHD therapy was associated with a decrease in the risk of fracture in children and adolescents treated by German pediatricians.

The role of incretin-based therapies in prediabetes: a review.

Science.gov (United States)

Ahmadieh, Hala; Azar, Sami T

2014-12-01

Prediabetes, a high-risk state for future development of diabetes, is prevalent globally. Abnormalities in the incretin axis are important in the progression of B-cell failure in type 2 diabetes. Incretin based therapy was found to improve B cell mass and glycaemic control in addition to having multiple beneficial effects on the systolic and diastolic blood pressure, weight loss in addition to their other beneficial effects on the liver and cardiovascular system. In prediabetes, several well-designed preventive trials have shown that lifestyle and pharmacologic interventions such as metformin, thiazolidinediones (TZD), acarbose and, nateglinide and orlistat, are effective in reducing diabetes development. In recent small studies, incretin based therapy (DPP IV inhibitors and GLP-1 agonists) have also been extended to patients with prediabetes since it was shown to better preserve B-cell function and mass in animal studies and in clinical trials and it was also shown to help maintain good long term metabolic control. Because of the limited studies and clinical experience, their side effects and costs currently guidelines do not recommend incretin-based therapies as an option for treatment in patients with prediabetes. With future clinical trials and studies they may be recommended for patients with impaired fasting glucose or impaired glucose tolerance. Copyright © 2014 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Planning Target Volume D95 and Mean Dose Should Be Considered for Optimal Local Control for Stereotactic Ablative Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Zhao, Lina [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhou, Shouhao [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Balter, Peter [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shen, Chan [Department of Health Service Research, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R.; Welsh, James D.; Lin, Steve H. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Joe Y., E-mail: jychang@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2016-07-15

Purpose: To identify the optimal dose parameters predictive for local/lobar control after stereotactic ablative radiation therapy (SABR) in early-stage non-small cell lung cancer (NSCLC). Methods and Materials: This study encompassed a total of 1092 patients (1200 lesions) with NSCLC of clinical stage T1-T2 N0M0 who were treated with SABR of 50 Gy in 4 fractions or 70 Gy in 10 fractions, depending on tumor location/size, using computed tomography-based heterogeneity corrections and a convolution superposition calculation algorithm. Patients were monitored by chest CT or positron emission tomography/CT and/or biopsy after SABR. Factors predicting local/lobar recurrence (LR) were determined by competing risk multivariate analysis. Continuous variables were divided into 2 subgroups at cutoff values identified by receiver operating characteristic curves. Results: At a median follow-up time of 31.7 months (interquartile range, 14.8-51.3 months), the 5-year time to local recurrence within the same lobe and overall survival rates were 93.8% and 44.8%, respectively. Total cumulative number of patients experiencing LR was 40 (3.7%), occurring at a median time of 14.4 months (range, 4.8-46 months). Using multivariate competing risk analysis, independent predictive factors for LR after SABR were minimum biologically effective dose (BED{sub 10}) to 95% of planning target volume (PTVD95 BED{sub 10}) ≤86 Gy (corresponding to PTV D95 physics dose of 42 Gy in 4 fractions or 55 Gy in 10 fractions) and gross tumor volume ≥8.3 cm{sup 3}. The PTVmean BED{sub 10} was highly correlated with PTVD95 BED{sub 10.} In univariate analysis, a cutoff of 130 Gy for PTVmean BED{sub 10} (corresponding to PTVmean physics dose of 55 Gy in 4 fractions or 75 Gy in 10 fractions) was also significantly associated with LR. Conclusions: In addition to gross tumor volume, higher radiation dose delivered to the PTV predicts for better local/lobar control. We recommend that both PTVD95 BED

Ethical and Safety Issues of Stem Cell-Based Therapy.

Science.gov (United States)

Volarevic, Vladislav; Markovic, Bojana Simovic; Gazdic, Marina; Volarevic, Ana; Jovicic, Nemanja; Arsenijevic, Nebojsa; Armstrong, Lyle; Djonov, Valentin; Lako, Majlinda; Stojkovic, Miodrag

2018-01-01

Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns. In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine. We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies. With previous derivation of induced pluripotent stem cells (iPSCs) this problem has been overcome, however current perspectives regarding clinical translation of iPSCs still remain. Unlimited differentiation potential of iPSCs which can be used in human reproductive cloning, as a risk for generation of genetically engineered human embryos and human-animal chimeras, is major ethical issue, while undesired differentiation and malignant transformation are major safety issues. Although clinical application of mesenchymal stem cells (MSCs) has shown beneficial effects in the therapy of autoimmune and chronic inflammatory diseases, the ability to promote tumor growth and metastasis and overestimated therapeutic potential of MSCs still provide concerns for the field of regenerative medicine. This review offers stem cell scientists, clinicians and patient's useful information and could be used as a starting point for more in-depth analysis of ethical and safety issues related to clinical application of stem cells.

[The influence of drug liberation from drug forms on local therapy of infected bone cavities].

Science.gov (United States)

Süss, W; Wehr, M

1984-09-01

With regard to an optimum local pharmaco-therapy in infected bone cavities, in vitro examinations by means of a flow model based on the half-change method had been performed to liberate Gentamycin from globular embeddings in polymethylmethacrylate. The Gentamycin had been determined in a micro-biological manner. The release behaviour of the polymere carrier could be controlled by adding Polyethylenglycol 400 as softener or butane dioldimethacrylate as wettener. Adding 20 vol.-% of Polyethylenglycol 400, the Gentamycin release could be increased to the 8-fold, whereas the addition of 5 vol.-% of butane dioldimethacrylate resulted in a decrease amounting to 7/8 exit value.

Radiation or chemoradiation: initial utility study of selected therapy for local advanced stadium cervical cancer

Science.gov (United States)

Pramitasari, D. A.; Gondhowiardjo, S.; Nuranna, L.

2017-08-01

This study aimed to compare radiation only or chemo radiation treatment of local advanced cervical cancers by examining the initial response of tumors and acute side effects. An initial assessment employed value based medicine (VBM) by obtaining utility values for both types of therapy. The incidences of acute lower gastrointestinal, genitourinary, and hematology side effects in patients undergoing chemoradiation did not differ significantly from those undergoing radiation alone. Utility values for patients who underwent radiation alone were higher compared to those who underwent chemoradiation. It was concluded that the complete response of patients who underwent chemoradiation did not differ significantly from those who underwent radiation alone.

[Acceptance and mindfulness-based cognitive-behavioral therapies].

Science.gov (United States)

Ngô, Thanh-Lan

2013-01-01

Cognitive behavioral therapy (CBT) is one of the main approaches in psychotherapy. It teaches the patient to examine the link between dysfunctional thoughts and maladaptive behaviors and to re- evaluate the cognitive biases involved in the maintenance of symptoms by using strategies such as guided discovery. CBT is constantly evolving in part to improve its' effectiveness and accessibility. Thus in the last decade, increasingly popular approaches based on mindfulness and acceptance have emerged. These therapies do not attempt to modify cognitions even when they are biased and dysfunctional but rather seek a change in the relationship between the individual and the symptoms. This article aims to present the historical context that has allowed the emergence of this trend, the points of convergence and divergence with traditional CBT as well as a brief presentation of the different therapies based on mindfulness meditation and acceptance. Hayes (2004) described three successive waves in behavior therapy, each characterized by "dominant assumptions, methods and goals": traditional behavior therapy, cognitive therapy and therapies based on mindfulness meditation and acceptance. The latter consider that human suffering occurs when the individual lives a restricted life in order avoid pain and immediate discomfort to the detriment of his global wellbeing. These therapies combine mindfulness, experiential, acceptance strategies with traditional behavior principles in order to attain lasting results. There are significant points of convergence between traditional CBT and therapies based on mindfulness meditation and acceptance. They are both empirically validated, based upon a theoretical model postulating that avoidance is key in the maintenance of psychopathology and they recommend an approach strategy in order to overcome the identified problem. They both use behavioral techniques in the context of a collaborative relationship in order to identify precise problems and to

Assessing Local Risk of Rifampicin-Resistant Tuberculosis in KwaZulu-Natal, South Africa Using Lot Quality Assurance Sampling.

Directory of Open Access Journals (Sweden)

Christine L Heidebrecht

Full Text Available KwaZulu-Natal (KZN has the highest burden of notified multidrug-resistant tuberculosis (MDR TB and extensively drug-resistant (XDR TB cases in South Africa. A better understanding of spatial heterogeneity in the risk of drug-resistance may help to prioritize local responses.Between July 2012 and June 2013, we conducted a two-way Lot Quality Assurance Sampling (LQAS study to classify the burden of rifampicin (RIF-resistant TB among incident TB cases notified within the catchment areas of seven laboratories in two northern and one southern district of KZN. Decision rules for classification of areas as having either a high- or low-risk of RIF resistant TB (based on proportion of RIF resistance among all TB cases were based on consultation with local policy makers.We classified five areas as high-risk and two as low-risk. High-risk areas were identified in both Southern and Northern districts, with the greatest proportion of RIF resistance observed in the northernmost area, the Manguzi community situated on the Mozambique border.Our study revealed heterogeneity in the risk of RIF resistant disease among incident TB cases in KZN. This study demonstrates the potential for LQAS to detect geographic heterogeneity in areas where access to drug susceptibility testing is limited.

Assessing Local Risk of Rifampicin-Resistant Tuberculosis in KwaZulu-Natal, South Africa Using Lot Quality Assurance Sampling.

Science.gov (United States)

Heidebrecht, Christine L; Podewils, Laura J; Pym, Alexander; Mthiyane, Thuli; Cohen, Ted

2016-01-01

KwaZulu-Natal (KZN) has the highest burden of notified multidrug-resistant tuberculosis (MDR TB) and extensively drug-resistant (XDR) TB cases in South Africa. A better understanding of spatial heterogeneity in the risk of drug-resistance may help to prioritize local responses. Between July 2012 and June 2013, we conducted a two-way Lot Quality Assurance Sampling (LQAS) study to classify the burden of rifampicin (RIF)-resistant TB among incident TB cases notified within the catchment areas of seven laboratories in two northern and one southern district of KZN. Decision rules for classification of areas as having either a high- or low-risk of RIF resistant TB (based on proportion of RIF resistance among all TB cases) were based on consultation with local policy makers. We classified five areas as high-risk and two as low-risk. High-risk areas were identified in both Southern and Northern districts, with the greatest proportion of RIF resistance observed in the northernmost area, the Manguzi community situated on the Mozambique border. Our study revealed heterogeneity in the risk of RIF resistant disease among incident TB cases in KZN. This study demonstrates the potential for LQAS to detect geographic heterogeneity in areas where access to drug susceptibility testing is limited.

Moving from Virtual Reality Exposure-Based Therapy to Augmented Reality Exposure-Based Therapy: A Review

OpenAIRE

Baus, Oliver; Bouchard, Stéphane

2014-01-01

This paper reviews the move from virtual reality exposure-based therapy to augmented reality exposure-based therapy (ARET). Unlike virtual reality (VR), which entails a complete virtual environment (VE), augmented reality (AR) limits itself to producing certain virtual elements to then merge them into the view of the physical world. Although, the general public may only have become aware of AR in the last few years, AR type applications have been around since beginning of the twentieth centur...

Impact of region contouring variability on image-based focal therapy evaluation

Science.gov (United States)

Gibson, Eli; Donaldson, Ian A.; Shah, Taimur T.; Hu, Yipeng; Ahmed, Hashim U.; Barratt, Dean C.

2016-03-01

Motivation: Focal therapy is an emerging low-morbidity treatment option for low-intermediate risk prostate cancer; however, challenges remain in accurately delivering treatment to specified targets and determining treatment success. Registered multi-parametric magnetic resonance imaging (MPMRI) acquired before and after treatment can support focal therapy evaluation and optimization; however, contouring variability, when defining the prostate, the clinical target volume (CTV) and the ablation region in images, reduces the precision of quantitative image-based focal therapy evaluation metrics. To inform the interpretation and clarify the limitations of such metrics, we investigated inter-observer contouring variability and its impact on four metrics. Methods: Pre-therapy and 2-week-post-therapy standard-of-care MPMRI were acquired from 5 focal cryotherapy patients. Two clinicians independently contoured, on each slice, the prostate (pre- and post-treatment) and the dominant index lesion CTV (pre-treatment) in the T2-weighted MRI, and the ablated region (post-treatment) in the dynamic-contrast- enhanced MRI. For each combination of clinician contours, post-treatment images were registered to pre-treatment images using a 3D biomechanical-model-based registration of prostate surfaces, and four metrics were computed: the proportion of the target tissue region that was ablated and the target:ablated region volume ratio for each of two targets (the CTV and an expanded planning target volume). Variance components analysis was used to measure the contribution of each type of contour to the variance in the therapy evaluation metrics. Conclusions: 14-23% of evaluation metric variance was attributable to contouring variability (including 6-12% from ablation region contouring); reducing this variability could improve the precision of focal therapy evaluation metrics.

Data mining for assessing the credit risk of local government units in Croatia

Directory of Open Access Journals (Sweden)

Silvija Vlah Jerić

2017-01-01

Full Text Available Over the past few decades, data mining techniques, especially artificial neural networks, have been used for modelling many real-world problems. This paper aims to test the performance of three methods: (1 an artificial neural network (ANN, (2 a hybrid artificial neural network and genetic algorithm approach (ANN-GA, and (2 the Tobit regression approach in determining the credit risk of local government units in Croatia. The evaluation of credit risk and prediction of debtor bankruptcy have long been regarded as an important topic in accounting and finance literature. In this research, credit risk is modelled under a regression approach unlike typical credit risk analysis, which is generally viewed as a classification problem. Namely, a standard evaluation of credit risk is not possible due to a lack of bankruptcy data. Thus, the credit risk of a local unit is approximated using the ratio of outstanding liabilities maturing in a given year to total expenditure of the local unit in the same period. The results indicate that the ANN-GA hybrid approach performs significantly better than the Tobit model by providing a significantly smaller average mean squared error. This work is beneficial to researchers and the government in evaluating a local government unit’s credit score.

Occupational Therapy Practitioners with Occupational Musculoskeletal Injuries: Prevalence and Risk Factors.

Science.gov (United States)

Alnaser, Musaed Z

2015-12-01

The purpose of this study was to examine the prevalence and risk factors of occupational musculoskeletal injuries (OMIs) among occupational therapy practitioners over a 12-month period. A self-administered questionnaire mailed to 500 randomly selected practicing occupational therapists (OTs) and occupational therapy assistants (OTAs) living in the state of Texas. A response rate of 38 % was attained with 192 questionnaires returned. In a 12-months working period, 23 % of occupational therapy practitioners experienced musculoskeletal injuries. Muscle strain (52 %) was most reported injury and lower back (32 %) was most injured body part. Years of practicing experience (t = 2.83, p = 0.01), and age x(2)(2, N = 192) = 8.28, p = 0.02 were found as significant factors associated with injuries among OTAs. No factors were significantly associated with injuries among OTs. Patient handling was the primary factor associated with injuries. Also, minimal experience and older age were concluded as risk factors that might contribute to OMIs.

Clinical and dosimetric results of three-dimensional image-guided and pulsed dose rate curie-therapy in locally advanced cervical cancers

International Nuclear Information System (INIS)

Mazeron, R.; Gilmore, J.; Dumas, I.; Abrous-Anane, S.; Haberer, S.; Verstraet, R.; Champoudry, J.; Martinetti, F.; Morice, P.; Haie-Meller, C.

2011-01-01

The authors report a review of data obtained between 2004 and 2009 on 130 women who had been treated by optimized pulsed-rate curie-therapy for a locally advanced cervical cancer. Results are discussed in terms of cancer stage, treatment (with or without concomitant chemotherapy), planning method (MRI, scanography), delivered doses in the clinical target volumes, surgery, relapse occurrence and localizations, global survival probability, local control, undesirable side effects, occurrence of intestine or urinary toxicity. It appears that the association of a concomitant chemo-radiotherapy and optimized curie-therapy results in a good local-regional control and a low toxicity level. Short communication

Mindfulness-Based Cognitive Therapy for severe Functional Disorders

DEFF Research Database (Denmark)

Fjorback, Lone Overby

MINDFULNESS-BASED COGNITIVE THERAPY FOR FUNCTIONAL DISORDERS- A RANDOMISED CONTROLLED TRIAL   Background: Mindfulness-Based Stress Reduction (MBSR) is a group skills-training program developed by Kabat-Zinn. It is designed to teach patients to become more aware of and relate differently...... to their thoughts, feelings, and bodily sensations. Randomised controlled studies of MBSR have shown mitigation of stress, anxiety, and dysphoria in general population and reduction in total mood disturbance and stress symptoms in a medical population. In Mindfulness Based Cognitive Therapy MBSR is recombined...... with cognitive therapy. Aim: To examine the efficacy of Mindfulness-Based Cognitive Therapy in severe Functional disorders, defined as severe Bodily Distress Disorder. Method: 120 patients are randomised to either Mindfulness Based Cognitive Therapy: a manualized programme with eight weekly 3 ½ hour group...