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Sample records for high-dose radioiodine therapy

  1. The Effect of High Dose Radioiodine Therapy on Formation of Radiation Retinopathy During Thyroid Cancer Treatment

    PubMed Central

    Kaçar Güveli, Tülay; Özkan, Sezer; Öner Tamam, Müge; Uyanık, Ercan; Ediz, Nurcan; Mülazımoğlu, Mehmet; Özpaçacı, Tevfik

    2014-01-01

    Objective: Non-thyroidal complication of high-dose radioiodine therapy for thyroid carcinoma might cause salivary and lacrimal gland dysfunction, which may be transient or permanent in a dose-dependent manner. However, radiation retinopathy complicating 131I therapy, has not been previously well characterized. The aim of this study was to evaluate the extent of retinal damage among patients who had received high doses of radioiodine treatment. Methods: Forty eyes of 20 patients (3 male, 17 female) who received 250-1000 mCi during 131I therapy and on ophthalmological follow up for a year after the last treatment were included in the study. Mean age of the study group was 50 years (range 25-70 years). In ophthalmologic examination, visual acuity was measured in order to determine visual loss. Intraocular pressure was measured in all the patients. Then lens examination was carried out with slit lamp biomicroscopy in order to investigate cataract or partial lens opacities. Fundus observation was carried out through the dilated pupil with slit lamp biomicroscopy using 90 D noncontact lens. Result: The best corrected visual aquity with Snellen chart was found as 1.0 in 36 eyes (90%) and between 0.6 and 0.9 (10%) in 4 eyes (10%). At the biomicroscopic fundus examination, retinal hemorrhage consistent with radiation retinopathy, microaneurysm, microinfarction, edema or exudation, vitreus hemorrhage, partial or total optical disc pallor indicating papillopathy in the optic disc were not observed in any of the eyes. Conclusion: This result indicates that there is not any significant correlation between repeated high-dose radioiodine therapy and radiation retinopathy in differentiated thyroid carcinomas. Even though there is not a significant restriction in use of higher doses of radioiodine therapy in differentiated thyroid carcinoma, more extensive studies are needed in order to obtain more accurate data on possible occurrence of retinopathy. PMID:25541931

  2. High-dose radioiodine treatment for differentiated thyroid carcinoma is not associated with change in female fertility or any genetic risk to the offspring

    SciTech Connect

    Bal, Chandrasekhar . E-mail: csbal@hotmail.com; Kumar, Ajay; Tripathi, Madhavi; Chandrashekar, Narayana; Phom, Hentok; Murali, Nadig R.; Chandra, Prem; Pant, Gauri S.

    2005-10-01

    Background: We tried to evaluate the female fertility and genetic risk to the offspring from the exposure to high-dose {sup 131}I by assessing the pregnancy outcomes and health status of the children of female patients with differentiated thyroid cancer who had received therapeutic doses of {sup 131}I. Materials and Methods: From 1967 to 2002, a total of 1,282 women had been treated with {sup 131}I. Of these patients, 692 (54%) were in the reproductive age group (18-45 years). Forty women had a total of 50 pregnancies after high-dose {sup 131}I. Age at presentation ranged from 16 to 36 years (mean, 23 {+-} 4 years). Histopathology was papillary thyroid cancer in 32 cases and follicular thyroid cancer in 8 cases. Results: Single high-dose therapy was given in 30 cases, 2 doses were given in 7 cases, 3 doses were given in 2 cases, and four doses were given in 1 case in which lung metastases had occurred. In 37 patients (92%), disease was successfully ablated before pregnancy. Ovarian absorbed-radiation dose calculated by the MIRD method ranged from 3.5 to 60 cGy (mean, 12 {+-} 11 cGy). The interval between {sup 131}I therapy and pregnancy varied from 7 to 120 months (37.4 {+-} 28.2 months). Three spontaneous abortions occurred in 2 women. Forty-seven babies (20 females and 27 males) were born. Forty-four babies were healthy with normal birth weight and normal developmental milestones. Twenty women delivered their first baby after {sup 131}I therapy. The youngest child in our series is 11 months of age, and the oldest is 8.5 years of age. Conclusions: Female fertility is not affected by high-dose radioiodine treatment, and the therapy does not appear to be associated with any genetic risks to the offspring.

  3. [Radioiodine therapy for Graves' disease: problems and new developments].

    PubMed

    Reiners, Christoph

    2004-05-01

    In Germany, patients with Graves' disease are usually treated with radioiodine after unsuccessful antithyroid drug medication, occurrence of side effects from antithyroid drugs or an increased risk from surgery. In patients with normal or only slightly enlarged thyroid glands (volume < or = 50 ml), radioiodine therapy is particularly effective. Radioiodine is the preferential treatment for Graves' patients with high titres of TSH-receptor antibodies and cigarette smoking. Children are still rarely treated with radioiodine in Germany. In contrast, treatment with radioiodine should be more liberally applied in elderly patients with subclinical hyperthyroidism and cardiac symptoms. Individual dosimetry to determine the therapeutic activity is mandatory in Germany. Patients with large goitres obviously need higher organ doses than patients with smaller goitres or normal thyroid glands. Antithyroid drug treatment may interfere with radioiodine therapy. Therefore, it is recommendable to withdraw antithyroid drugs several days before treatment with radioiodine is initiated (and a preceding radioiodine uptake test is performed). In patients with Graves' orbitopathy prophylaxis with corticosteroids can prevent the worsening of symptoms that may be induced by radioiodine treatment. Currently, a risk adapted procedure is recommended according to which prophylactic medication with corticosteroids before applying radioiodine treatment is not necessary in patients with symptoms of orbitopathy and lack of other risk factors (cigarette smoking, in particular). Present results suggest that the risks of radioiodine treatment in Graves' disease patients are very low, while at the same time the cost-effectiveness of this treatment regimen is high. PMID:15255314

  4. High-Dose Radioiodine Outpatient Treatment: An Initial Experience in Thailand

    PubMed Central

    Nantajit, Danupon; Saengsuda, Sureerat; NaNakorn, Pattama; Saengsuda, Yuthana

    2015-01-01

    Objective(s): The aim of this study was to determine whether high-dose radioactive iodine (Na131I) outpatient treatment of patients with thyroid carcinoma is a pragmatically safe approach, particularly for the safety of caregivers. Methods: A total of 79 patients completed the radiation-safety questionnaires prior to receiving high-dose radioactive iodine treatment. The questionnaire studied the subjects’ willingness to be treated as outpatients, along with the radiation safety status of their caregivers and family members. In patients, who were selected to be treated as outpatients, both internal and external radiation exposures of their primary caregivers were measured, using thyroid uptake system and electronic dosimeter, respectively. Results: Overall, 62 out of 79 patients were willing to be treated as outpatients; however, only 44 cases were eligible for the treatment. The primary reason was that the patients did not use exclusive, separated bathrooms. The caregivers of 10 subjects, treated as outpatients, received an average radiation dose of 138.1 microsievert (mSv), which was almost entirely from external exposure; the internal radiation exposures were mostly at negligible values. Therefore, radiation exposure to caregivers was significantly below the public exposure limit (1 mSv) and the recommended limit for caregivers (5 mSv). Conclusion: A safe 131I outpatient treatment in patients with thyroid carcinoma could be achieved by selective screening and providing instructions for patients and their caregivers.

  5. High dose bystander effects in spatially fractionated radiation therapy

    PubMed Central

    Asur, Rajalakshmi; Butterworth, Karl T.; Penagaricano, Jose A.; Prise, Kevin M.; Griffin, Robert J.

    2014-01-01

    Traditional radiotherapy of bulky tumors has certain limitations. Spatially fractionated radiation therapy (GRID) and intensity modulated radiotherapy (IMRT) are examples of advanced modulated beam therapies that help in significant reductions in normal tissue damage. GRID refers to the delivery of a single high dose of radiation to a large treatment area that is divided into several smaller fields, while IMRT allows improved dose conformity to the tumor target compared to conventional three-dimensional conformal radiotherapy. In this review, we consider spatially fractionated radiotherapy approaches focusing on GRID and IMRT, and present complementary evidence from different studies which support the role of radiation induced signaling effects in the overall radiobiological rationale for these treatments. PMID:24246848

  6. High-dose enzyme replacement therapy in murine Hurler syndrome.

    PubMed

    Ou, Li; Herzog, Tyler; Koniar, Brenda L; Gunther, Roland; Whitley, Chester B

    2014-02-01

    Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease that is systemic, including progressive neurodegeneration, mental retardation and death before the age of 10 years. MPS I results from deficiency of α-L-iduronidase (IDUA) in lysosomes and subsequent accumulation of glycosaminoglycans (GAG). Clinical enzyme replacement therapy (ERT) with intravenous laronidase reverses some aspects of MPS I disease (e.g., hepatomegaly, splenomegaly, glycosaminoglycanuria) and ameliorates others (e.g., pulmonary function, cardiac disease, arthropathy, exercise tolerance). However, neurologic benefits are thought to be negligible because the blood-brain barrier (BBB) blocks enzyme from reaching the central nervous system (CNS). We considered the possibility that a very high dose of intravenous laronidase might be able to traverse the BBB in small quantities, and provide some metabolic correction in the brain. To address this question, high-dose laronidase was administered (11.6 mg/kg, once per week, 4 weeks) to adult MPS I mice. IDUA enzyme activity in the cortex of treated mice increased to 97% of that in wild type mice (p<0.01). GAG levels in cortex were reduced by 63% of that from untreated MPS I mice (p<0.05). Further, immunohistochemical analysis showed that treatment reduced secondary GM3-ganglioside accumulation in treated MPS I mice. Water T-maze tests showed that the learning abnormality in MPS I mice was reduced (p<0.0001). In summary, repeated, high-dose ERT facilitated laronidase transit across the BBB, reduced GAG accumulation within the CNS, and rescued cognitive impairment. PMID:24100243

  7. Assessments for High Dose Radionuclide Therapy Treatment Planning

    SciTech Connect

    Fisher, Darrell R.

    2003-10-01

    Advances in the biotechnology of cell-specific targeting of cancer, and the increased number of clinical trials involving treatment of cancer patients with radiolabeled antibodies, peptides, and similar delivery vehicles have led to an increase in the number of high-dose radionuclide therapy procedures. Optimized radionuclide therapy for cancer treatment is based on the concept of absorbed dose to the dose-limiting normal organ or tissue. The limiting normal tissue is often the red marrow, but it may sometimes be lungs, liver, intestinal tract, or kidneys. Appropriate treatment planning requires assessment of radiation dose to several internal organs and tissues, and usually involves biodistribution studies in the patient using a tracer amount of radionuclide bound to the targeting agent and imaged at sequential time points using a planar gamma camera. Time-activity curves are developed from the imaging data for the major organs tissues of concern, for the whole body, and sometimes for selected tumors. Patient-specific factors often require that dose estimates be customized for each patient. The Food and Drug Administration regulates the experimental use of investigational new drugs and requires reasonable calculation of radiation absorbed dose to the whole body and to critical organs using methods prescribed by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. Review of high-dose studies in the U.S. and elsewhere shows that 1) some studies are conducted with minimal dosimetry, 2) the marrow dose is difficult to establish and is subject to large uncertainties, and 3) despite the general availability of MIRD software, internal dosimetry methods are often inconsistent from one clinical center to another.

  8. Wernicke's encephalopathy in a child with high dose thiamine therapy

    PubMed Central

    Park, So Won; Yi, Yoon Young; Han, Jung Woo; Kim, Heung Dong; Lee, Joon Soo

    2014-01-01

    Wernicke's encephalopathy is an acute neurological disorder characterized by mental confusion, oculomotor dysfunction, and ataxia. It has been reported in individuals with alcohol dependence, hyperemesis gravidarum, and prolonged parenteral nutrition without vitamin supplementation. Here we present the case of a 13-year-old male patient with neuroblastoma and a history of poor oral intake and nausea for 3 months. After admission, he showed gait disturbances, nystagmus, and excessive dizziness; his mental state, however, indicated he was alert, which did not fit the classical triad of Wernicke's encephalopathy. A diagnosis of Wernicke's encephalopathy was made only after brain magnetic resonance imaging and serum thiamine level analyses were performed. The patient's symptoms remained after 5 days of treatment with 100-mg thiamine once daily; thus, we increased the dosage to 500 mg 3 times daily, 1,500 mg per day. His symptoms then improved after 20 days of replacement therapy. This case report describes a pediatric patient who was promptly diagnosed with Wernicke's encephalopathy, despite only 2 suspicious symptoms, and who completely recovered after high doses of thiamine were given intravenously. PMID:25550705

  9. Radioiodine therapy of hyperthyroidism precludes thallium-201 myocardial scintigraphy

    SciTech Connect

    Orzel, J.A.; Kruyer, W.B.; Borchert, R.D.

    1987-02-01

    The authors attempted to perform Tl-201 myocardial perfusion scintigraphy in a 42-year-old man 23 and 35 days after he received 9.8 mCi of oral I-131 for documented Graves' disease. Interference from primary and scattered photons from residual thyroid I-131 made Tl-201 myocardial scintigraphy technically impossible. A series of phantom and patient studies using I-131 and Tl-201 were performed, yielding guidelines for planning Tl-201 myocardial scintigraphy following radioiodine therapy.

  10. Acute and long-term effects of radioiodine therapy on serum levels of calcitonin

    SciTech Connect

    Franke, A.; Oeff, K.

    1984-01-01

    The purpose of this study is to establish data on the radiosensitivity of thyroid C cells and medullary carcinoma of the thyroid (MCT) as reflected by the alterations in serum concentrations of calcitonin (Ct) after radioiodine therapy. Serum levels of Ct were measured by radioimmunoassay in 1437 patients subjected to diagnostic and therapeutic procedures for thyroid diseases. The effect of low dose and of high dose radioiodine therapy (RLO, RHI) was studied in 158 patients with hyperthyroidism and in 84 patients with thyroid cancer, respectively. RLO and RHI were followed by significant alterations in the distribution of Ct values. RLO decreased the occurrence of high values. RHI was followed by the absence of high concentrations and a substantial reduction in normal levels. The effect of RLO was confirmed in 47 patients by comparing their individual levels before and 8 weeks after RLO, the means +- SD being 24.3+-8.3 and 12.6+-5.7 pmol/l, respectively (p<0.001). In 30 patients followed up for late onset hypothyroidism who had been treated by RLO 10-25 years ago, the concentrations of Ct were almost normal (mean +- SD 16.6 +- 5.7 pmol/l).

  11. Response to Radioiodine Therapy for Thyrotoxicosis: Disparate Outcomes for an Indigenous Population

    PubMed Central

    Conaglen, John V.

    2016-01-01

    Despite 70 years of experience treating thyrotoxic patients with radioiodine not all patients are successfully treated by a single dose. Multiple factors predicting radioiodine efficacy have been reported. The aim of this study was to assess whether ethnicity was associated with radioiodine response. A retrospective review was performed of patients who received radioiodine therapy for thyrotoxicosis from 1 January 2008 to 31 December 2010 and had follow-up available of a minimum of 12 months. 224 patients were included, 82.4% female, and 63.7% had Graves's disease. Radioiodine failed in 21.5% of patients overall, with a higher failure rate in the indigenous population (35.2%). When controlling for other influencing factors by logistic regression, there continued to be an increased risk for the indigenous group (OR 2.82) and those treated with antithyroid drugs following radioiodine (OR 2.04). Younger age was also associated with an increased risk of failing radioiodine therapy (OR 0.97 for each year of age). Cure rates following radioiodine were lower for indigenes independent of factors known to affect radioiodine outcome. This is the first report demonstrating ethnicity as a possible independent variable for radioiodine efficacy. Further work is needed to investigate the cause of this difference. PMID:27446210

  12. Response to Radioiodine Therapy for Thyrotoxicosis: Disparate Outcomes for an Indigenous Population.

    PubMed

    Tamatea, Jade A U; Conaglen, John V; Elston, Marianne S

    2016-01-01

    Despite 70 years of experience treating thyrotoxic patients with radioiodine not all patients are successfully treated by a single dose. Multiple factors predicting radioiodine efficacy have been reported. The aim of this study was to assess whether ethnicity was associated with radioiodine response. A retrospective review was performed of patients who received radioiodine therapy for thyrotoxicosis from 1 January 2008 to 31 December 2010 and had follow-up available of a minimum of 12 months. 224 patients were included, 82.4% female, and 63.7% had Graves's disease. Radioiodine failed in 21.5% of patients overall, with a higher failure rate in the indigenous population (35.2%). When controlling for other influencing factors by logistic regression, there continued to be an increased risk for the indigenous group (OR 2.82) and those treated with antithyroid drugs following radioiodine (OR 2.04). Younger age was also associated with an increased risk of failing radioiodine therapy (OR 0.97 for each year of age). Cure rates following radioiodine were lower for indigenes independent of factors known to affect radioiodine outcome. This is the first report demonstrating ethnicity as a possible independent variable for radioiodine efficacy. Further work is needed to investigate the cause of this difference. PMID:27446210

  13. [High-dose buprenorphine for outpatient palliative pain therapy].

    PubMed

    Gastmeier, K; Freye, E

    2009-04-01

    The case of a 78-year-old patient with cancer-related pain and additionally mixed-pain syndrome is presented. Pain therapy with buprenorphine TTS 210 microg/h every 3 days was sufficient in the beginning, later the therapy was changed because of increasing problems of tape fixing during fever periods under chemotherapy to a continuous infusion of buprenorphine intravenously via an external medication pump. During the course of therapy it became necessary to increase the dose to 99.9 mg/day buprenorphine. Under this medication a sufficient pain reduction (median NRS 2-3) over a period of 135 days could be achieved. At the same time the patient was vigilant and cooperative without signs of intoxication until the end of life at home in the presence of his family.If no signs of intoxication occur under extreme opioid therapy and a sufficient pain therapy can be achieved, a rotation to another opioid is not necessary. However, outpatient palliative care requires a frequent adaptation to the individually varying opioid demand of the patient and time-consuming nursing care. PMID:19066981

  14. Thyroid cancer radioiodine therapy: health service performance and radiation safety.

    PubMed

    Vogiatzi, S; Liossis, A; Lamprinakou, M

    2015-07-01

    Greek Atomic Energy Commission collected data related to radioiodine I-131 therapy (RAIT) delivery to differentiated thyroid carcinoma patients, for the period 2003-13, corresponding to 100 % of hospitals at national level. Radiation safety and health service performance outcome indicators were assessed. The numbers of hospitals and nuclear medicine (NM) therapy wards, as well as RAIT annual frequencies, have increased. Geographical inhomogeneous distribution of existing infrastructure is recorded. In some cases, the observed inefficient use of NM therapy wards seems to be due to lack of human resources (e.g. nurses). Regular assessment of appropriate key indicators could serve as a useful tool for radiation safety monitoring and health service performance improvement. PMID:25809109

  15. Efficacy of high-dose methylprednisolone pulse therapy in the treatment of enterovirus 71 encephalitis.

    PubMed

    Zhang, Guangyou; Wang, Jiwen; Yao, Guo; Shi, Baohai

    2016-07-01

    To investigate the efficacy of high-dose methylprednisolone pulse therapy in the treatment of Enterovirus 71 (EV71) encephalitis. To determine whether high-dose methylprednisolone pulse therapy should be used, 80 cases of pediatric patients with EV71 encephalitis were randomly divided into steroid pulse therapy group and non-steroid pulse therapy group and their clinical information was compared using statistic analysis. There was no statistical difference in the duration of fever, duration of nervous system involvement, duration of hospital stay, blood pressure, and cure rates between the two groups (p>0.05). The heart rate, respiratory rate, white blood cell counts and blood glucose of the steroid pulse therapy group were significantly higher than those of the non-steroid pulse therapy group (p<0.05). High-dose steroid pulse therapy to treat EV71 encephalitis can't shorten the course or improve the prognosis of the disease. In contrast, it has side effects and might aggravate disease condition or interfere with disease diagnosis. Our study suggested that there is no beneficial effect to use high-dose steroid pulse therapy for the treatment of EV71 encephalitis. PMID:27592493

  16. Comparison between conventional salvage therapy and high-dose therapy with autografting for recurrent or refractory Hodgkin's disease.

    PubMed

    Yuen, A R; Rosenberg, S A; Hoppe, R T; Halpern, J D; Horning, S J

    1997-02-01

    Sixty patients with Hodgkin's disease, refractory to or at first recurrence after chemotherapy, received cytoreductive therapy followed by high-dose etoposide, cyclophosphamide and either total body irradiation or carmustine and autografting (median follow-up, 3.6 years; range, 1.1 to 7.5 years). A matched conventional salvage group of 103 patients was selected from patients treated at Stanford University Medical Center between January 1976 and January 1989 (median follow-up, 10.3 years; range, 3.0 to 15.7 years). Overall survival (OS), event-free survival (EFS), and freedom from progression (FFP) at 4 years follow-up favored patients who received high-dose therapy compared with conventional salvage treatment (OS: 54% v 47%, P = .25; EFS: 53% v 27%, P < .01; FFP: 62% v 32%, P < .01). In Cox regression analysis, response to cytoreductive or salvage therapy and B symptoms at relapse were the most important predictors of OS. The use of high-dose therapy at relapse, a longer duration of remission, and favorable response to cytoreductive or salvage therapy were most predictive of superior FFP and EFS. These data from a single institution comparing conventional and high-dose therapy in matched patients demonstrate an advantage for high-dose therapy and autografting in the sustained control of Hodgkin's disease. As with primary therapy, it is difficult to demonstrate a statistically significant survival advantage, despite an apparently superior cure rate. However, patients failing induction therapy or relapsing within 1 year benefited significantly from high-dose therapy by all outcome measures (OS, EFS, FFP). As the transplant-related mortality rates decline in Hodgkin's disease, it is predicted that cure rates and late effects will become ultimate determinants of the success of high-dose therapy and autografting. PMID:9028312

  17. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning.

    PubMed

    Engebretsen, Kristin M; Kaczmarek, Kathleen M; Morgan, Jenifer; Holger, Joel S

    2011-04-01

    INTRODUCTION. High-dose insulin therapy, along with glucose supplementation, has emerged as an effective treatment for severe beta-blocker and calcium channel-blocker poisoning. We review the experimental data and clinical experience that suggests high-dose insulin is superior to conventional therapies for these poisonings. PRESENTATION AND GENERAL MANAGEMENT. Hypotension, bradycardia, decreased systemic vascular resistance (SVR), and cardiogenic shock are characteristic features of beta-blocker and calcium-channel blocker poisoning. Initial treatment is primarily supportive and includes saline fluid resuscitation which is essential to correct vasodilation and low cardiac filling pressures. Conventional therapies such as atropine, glucagon and calcium often fail to improve hemodynamic status in severely poisoned patients. Catecholamines can increase blood pressure and heart rate, but they also increase SVR which may result in decreases in cardiac output and perfusion of vascular beds. The increased myocardial oxygen demand that results from catecholamines and vasopressors may be deleterious in the setting of hypotension and decreased coronary perfusion. METHODS. The Medline, Embase, Toxnet, and Google Scholar databases were searched for the years 1975-2010 using the terms: high-dose insulin, hyperinsulinemia-euglycemia, beta-blocker, calcium-channel blocker, toxicology, poisoning, antidote, toxin-induced cardiovascular shock, and overdose. In addition, a manual search of the Abstracts of the North American Congress of Clinical Toxicology and the Congress of the European Association of Poisons Centres and Clinical Toxicologists published in Clinical Toxicology for the years 1996-2010 was undertaken. These searches identified 485 articles of which 72 were considered relevant. MECHANISMS OF HIGH-DOSE INSULIN BENEFIT. There are three main mechanisms of benefit: increased inotropy, increased intracellular glucose transport, and vascular dilatation. EFFICACY OF HIGH-DOSE

  18. Peripheral blood progenitor cell transplantation in multiple myeloma following high-dose melphalan-based therapy.

    PubMed

    Goldschmidt, H; Hegenbart, U; Wallmeier, M; Hohaus, S; Engenhart, R; Wannenmacher, M; Haas, R

    1998-01-01

    The objective of our study was to evaluate the efficacy and toxicity of a high-dose melphalan-based therapy with or without total body irradiation (TBI) followed by peripheral blood progenitor cell (PBPC) transplantation in patients with multiple myeloma. Between June 1992 and June 1996, 104 patients (71 male, 33 female) with a median age of 51 years (range 30-65 years) underwent transplantation at our center. PBPC were mobilized using high-dose chemotherapy followed by treatment with G-CSF. Fifty patients were treated with TBI+melphalan 140 mg/m2 while 54 patients received melphalan 200 mg/m2. Following PBPC autografting, the median time to attainment of platelets > or = 20 x 10(9)/l and neutrophils > or = 0.5 x 10(9)/l was 11 and 14 days, with no difference between the treatment groups. In the TBI group significantly longer periods of total parenteral nutrition were required due to the occurrence of severe mucositis. Two patients from the TBI group died of transplantation-related complications. Following high-dose treatment, remission state improved in 43 out of 102 patients. No statistically significant advantage in reaching complete or partial remission was observed with TBI+high-dose melphalan compared to the treatment with high-dose melphalan alone. The optimal high-dose treatment, with particular reference to the inclusion or omission of TBI, should be prospectively investigated. PMID:9304704

  19. Transient radiation effects following high dose I-131 therapy for differentiated thyroid cancer (DTC)

    SciTech Connect

    Khan, S.; Waxman, A.; Ramanna, L.

    1994-05-01

    There is limited information regarding the incidence of post-I-131 therapeutic side effects in pts. undergoing high-dose I-131 therapy for DTC. The purpose of the current study is to characterize side effects experienced by patients following 150 mCi.

  20. Early Angiographic Resolution of Cerebral Vasospasm with High Dose Intravenous Milrinone Therapy

    PubMed Central

    Zeiler, F. A.; Silvaggio, J.

    2015-01-01

    Background. Treatment of symptomatic delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is difficult. Recent studies suggest intravenous (IV) high dose milrinone as a potential therapy. The timing to angiographic response with this is unclear. Methods. We reviewed the chart of one patient admitted for SAH who developed symptomatic DCI and was treated with high dose IV milrinone. Results. A 66-year-old female was admitted with a Hunt and Hess clinical grade 4, World Federation of Neurological Surgeons (WFNS) clinical grade 4, and SAH secondary to a left anterior choroidal artery aneurysm which was clipped. After bleed day 6, the patient developed symptomatic DCI. We planned for angioplasty of the proximal segments. We administered high dose IV milrinone bolus followed by continuous infusion which led to clinical improvement prior to angiography. The angiogram performed 1.5 hours after milrinone administration displayed resolution of the CT angiogram and MRI based cerebral vasospasm such that further intra-arterial therapy was aborted. She completed 6 days of continuous IV milrinone therapy, was transferred to the ward, and subsequently rehabilitated. Conclusions. High dose IV milrinone therapy for symptomatic DCI after SAH can lead to rapid neurological improvement with dramatic early angiographic improvement of cerebral vasospasm. PMID:26457209

  1. Can peptide receptor radionuclide therapy (PRRT) be useful in radioiodine-refractory differentiated thyroid cancer?

    PubMed

    Campennì, Alfredo; Pignata, Salvatore A; Baldari, Sergio

    2015-11-01

    We report on a 70-year-old man affected by radioiodine-refractory differentiated thyroid cancer (DTC) in whom metastases were treated by peptide receptor radionuclide therapy (PRRT). Seven years before, patient had undergone total thyroidectomy. Pathological examination was conclusive for DTC. The patient underwent some radioiodine treatments (RaIT). The last post-therapy whole body scan (pT-WBS) performed five days after RaIT did not show abnormal radioiodine uptake but serum thyroglobulin (Tg) value was high in absence of thyroglobulin-antibodies (Tg-Ab). In-111 DTPA-pentetreotide scintigraphy showed several lung lesions with high somatostatin receptor density. Patient underwent PRRT using Lu-177 DOTATOC. pT-WBS scan confirmed the metastases already demonstrated by In-111 DTPA pentetreotide but radioiodine negative. PMID:25471282

  2. Outcome of Radioiodine Therapy in a West African Population

    PubMed Central

    Onimode, Yetunde A.; Ankrah, Alfred; Adedapo, Kayode S.

    2016-01-01

    Hyperthyroidism continues to be a pressing public health concern in West Africa. Its prevalence in Africa has been quoted as 1.2%-9.9%, with Graves’ disease as its most common cause. Radioiodine-131 (RAI) therapy of hyperthyroidism recently commenced in two government hospitals in Ghana and Nigeria. This is a retrospective analysis of consecutive patients treated with RAI for primary hyperthyroidism at the National Centre for Radiotherapy and Nuclear Medicine (NCRNM) from 2008-2013, and in the University College Hospital (UCH) from 2006-2013. Cure was defined as euthyroidism or hypothyroidism occurring at 6 months post-RAI. Data were analysed using SPSS version 21 and Epi Info version, categorical data were evaluated with the Chi-square test and Fisher's exact test. 94 patients were studied, aged 20-74 years; 78 were females, and 16 were males. 38 were Ghanaian and 56 Nigerian. The presence of thyroid-associated ophthalmopathy (TAO) made cure less likely (χ2 P = 0.006, odds ratio = 0.118; 95% confidence interval, 0.027-0.518). Other factors assessed proved to be insignificant. Our findings suggest that hyperthyroid patients with TAO will benefit from a higher RAI dose than their counterparts without TAO. PMID:26912975

  3. Outcome of Radioiodine Therapy in a West African Population.

    PubMed

    Onimode, Yetunde A; Ankrah, Alfred; Adedapo, Kayode S

    2016-01-01

    Hyperthyroidism continues to be a pressing public health concern in West Africa. Its prevalence in Africa has been quoted as 1.2%-9.9%, with Graves' disease as its most common cause. Radioiodine-131 (RAI) therapy of hyperthyroidism recently commenced in two government hospitals in Ghana and Nigeria. This is a retrospective analysis of consecutive patients treated with RAI for primary hyperthyroidism at the National Centre for Radiotherapy and Nuclear Medicine (NCRNM) from 2008-2013, and in the University College Hospital (UCH) from 2006-2013. Cure was defined as euthyroidism or hypothyroidism occurring at 6 months post-RAI. Data were analysed using SPSS version 21 and Epi Info version, categorical data were evaluated with the Chi-square test and Fisher's exact test. 94 patients were studied, aged 20-74 years; 78 were females, and 16 were males. 38 were Ghanaian and 56 Nigerian. The presence of thyroid-associated ophthalmopathy (TAO) made cure less likely (χ(2) P = 0.006, odds ratio = 0.118; 95% confidence interval, 0.027-0.518). Other factors assessed proved to be insignificant. Our findings suggest that hyperthyroid patients with TAO will benefit from a higher RAI dose than their counterparts without TAO. PMID:26912975

  4. Spatially resolved measurement of high doses in microbeam radiation therapy using samarium doped fluorophosphate glasses

    SciTech Connect

    Okada, Go; Morrell, Brian; Koughia, Cyril; Kasap, Safa; Edgar, Andy; Varoy, Chris; Belev, George; Wysokinski, Tomasz; Chapman, Dean

    2011-09-19

    The measurement of spatially resolved high doses in microbeam radiation therapy has always been a challenging task, where a combination of high dose response and high spatial resolution (microns) is required for synchrotron radiation peaked around 50 keV. The x-ray induced Sm{sup 3+}{yields} Sm{sup 2+} valence conversion in Sm{sup 3+} doped fluorophosphates glasses has been tested for use in x-ray dosimetry for microbeam radiation therapy. The conversion efficiency depends almost linearly on the dose of irradiation up to {approx}5 Gy and saturates at doses exceeding {approx}80 Gy. The conversion shows strong correlation with x-ray induced absorbance of the glass which is related to the formation of phosphorus-oxygen hole centers. When irradiated through a microslit collimator, a good spatial resolution and high ''peak-to-valley'' contrast have been observed by means of confocal photoluminescence microscopy.

  5. Treatment of Graves' ophthalmopathy with high-dose intravenous methylprednisolone pulse therapy.

    PubMed

    Nagayama, Y; Izumi, M; Kiriyama, T; Yokoyama, N; Morita, S; Kakezono, F; Ohtakara, S; Morimoto, I; Okamoto, S; Nagataki, S

    1987-12-01

    This preliminary study was undertaken to investigate the efficacy of high-dose iv methylprednisolone pulse therapy in 5 patients with Graves' ophthalmopathy. One gram of methylprednisolone sodium succinate was given iv daily for 3 successive days. The 3-day infusion was repeated 3 to 7 times at intervals of 1 week; total duration of pulse therapy was 3 to 7 weeks. The clinical improvement of eye involvements by pulse therapy was assessed immediately after the last pulse therapy. The clinical assessment of the effect of pulse therapy for Graves' ophthalmopathy showed a good response in 3 patients, a fair response in one, and no response in one. However, in one patient, who was judged to show no response, complete improvement of the enlarged extraocular muscle was observed on orbital computed tomography. Moreover, two patients, who have been followed without any other therapies, showed no relapse of eye involvements for 32 and 10 months, respectively. Although it is impossible to determine whether pulse therapy is more effective than other immunosuppressive therapies, the results of this preliminary study suggest that pulse therapy may be a good immunosuppressive therapy for Graves' ophthalmopathy too. Controlled studies are desired. PMID:3321820

  6. Challenges of Using High-Dose Fractionation Radiotherapy in Combination Therapy

    PubMed Central

    Yang, Ying-Chieh; Chiang, Chi-Shiun

    2016-01-01

    Radiotherapy is crucial and substantially contributes to multimodal cancer treatment. The combination of conventional fractionation radiotherapy (CFRT) and systemic therapy has been established as the standard treatment for many cancer types. With advances in linear accelerators and image-guided techniques, high-dose fractionation radiotherapy (HFRT) is increasingly introduced in cancer centers. Clinicians are currently integrating HFRT into multimodality treatment. The shift from CFRT to HFRT reveals different effects on the tumor microenvironment and responses, particularly the immune response. Furthermore, the combination of HFRT and drugs yields different results in different types of tumors or using different treatment schemes. We have reviewed clinical trials and preclinical evidence on the combination of HFRT with drugs, such as chemotherapy, targeted therapy, and immune therapy. Notably, HFRT apparently enhances tumor cell killing and antigen presentation, thus providing opportunities and challenges in treating cancer. PMID:27446811

  7. Combined methotrexate and high-dose vincristine chemotherapy with radiation therapy for small cell bronchogenic carcinoma

    SciTech Connect

    Holoye, P.Y.; Libnoch, J.A.; Anderson, T.; Cox, J.D.; Byhardt, R.W.; Hoffmann, R.G.

    1985-04-01

    The addition of methotrexate to a previously described regimen of cyclophosphamide, Adriamycin (doxorubicin), and high-dose vincristine (VAC) was tested in 50 evaluable patients with small cell bronchogenic carcinoma. Prophylactic whole brain radiation therapy was given during the first chemotherapy course and consolidation radiation therapy was given to the mediastinum and primary site after achieving partial or complete remission. The addition of methotrexate did not improve the incidence of complete remission as compared to a previous regimen without it. The addition of radiation therapy improved the local control rate. The high-dose vincristine in this and a previous CAV study improved the incidence of complete remission in both limited and extensive disease presentation as compared with the authors previous experience and induced an acceptable and reversible neurotoxicity. Moderate dose consolidation radiotherapy to the lung primary and mediastinum was effective in improving local control. The distinction between limited and extensive disease was found to be vague, as 22% of the patients could be shifted from one group to the other depending on definition. The evaluation of the various staging procedures indicates that bone scan gave a small number of truly abnormal tests. Isotopic brain and liver-spleen scan could be duplicated by computerized axial tomography (CAT). CAT scan of abdomen disclosed unexpected extension to the retroperitoneal nodes and adrenals.

  8. Economic and social effects of high-dose buprenorphine substitution therapy. Six-month results.

    PubMed

    Lavignasse, Pierre; Lowenstein, William; Batel, Philippe; Constant, Marie-Véronique; Jourdain, Jean-Jacques; Kopp, Pierre; Reynaud-Maurupt, Catherine; Riff, Bertrand; Videau, Benjamin; Mucchielli, Alain

    2002-05-01

    The purpose of this study was to analyze the impact of high-dose buprenorphine substitution therapy in opiate-dependent patients in terms of use of psychoactive substances, associated risks, social integration, and the social cost generated by the use of these substances. This was a longitudinal quantitative survey carried out in 1083 patients who were evaluated at three times: at the beginning of substitution therapy (D0), at 6 months and then at 12 months follow up (M6, M12). Data were collected with an anonymous self-administered questionnaire, completed in the presence of an investigating physician. Results demonstrated that patients treated with high-dose buprenorphine for 6 months, consumed fewer psychoactive drugs (heroin, cocaine, benzodiazepines) and had fewer associated risks. Additionally, several criteria involved in social integration showed improvement; morbidity and mortality decreased after the first 6 months of substitution therapy. These improvements were followed by a reduction in the social cost of drug use generated by the group of patients considered. These initial results require confirmation in the final analysis of the study taking into account the 12-month follow up. PMID:12218879

  9. Impact of cytogenetic classification on outcomes following early high-dose therapy in multiple myeloma.

    PubMed

    Kaufman, G P; Gertz, M A; Dispenzieri, A; Lacy, M Q; Buadi, F K; Dingli, D; Hayman, S R; Kapoor, P; Lust, J A; Russell, S; Go, R S; Hwa, Y L; Kyle, R A; Rajkumar, S V; Kumar, S K

    2016-03-01

    Early high-dose therapy (HDT), consisting of high-dose melphalan and autologous stem cell transplantation following doublet or triplet novel agent induction, is a preferred management strategy for transplant-eligible myeloma patients. We set out to examine the utility of the current fluorescence in situ hybridization (FISH)-based risk stratification in a homogenously treated population of transplant-eligible myeloma patients receiving novel induction regimens and early HDT with or without posttransplant maintenance therapy. FISH was available in 409 patients at the time of diagnosis for patients receiving HDT within 12 months of diagnosis. We present comprehensive outcomes for chromosome 14 translocations and 17p abnormalities that both support and refute current risk stratification models. In contrast to its current classification as a marker of 'standard risk' (SR), t(11;14) was associated with inferior overall survival (OS) when compared with the classical SR cohort. The use of novel agent maintenance therapy (bortezomib or lenalidomide) following early HDT ameliorates the negative prognostic value of high-risk (HR) cytogenetic markers. HR patients who received maintenance following early HDT had similar OS compared with the SR cohort at 5 years. PMID:26487275

  10. Radioprotective agents for the prevention of side effects induced by radioiodine-131 therapy.

    PubMed

    Noaparast, Zohreh; Hosseinimehr, Seyed Jalal

    2013-08-01

    Radioiodine 131 ((131)I) has been used worldwide for the ablation of remnant thyroidal tissue after surgery or as the first-line treatment for Graves' disease. Although the use of (131)I is becoming increasingly prevalent, there is evidence suggesting that this treatment is associated with side effects such as salivary gland dysfunction and an increased risk of leukemia. This article aims to review the potential use of radioprotective agents and the side effects induced by (131)I therapy. Several synthetic and natural compounds have been investigated in preclinical and clinical studies. The protective agents reduced the toxicity of (131)I, mainly in the salivary glands, and mitigated the genetic damage through different mechanisms. There are limited clinical studies evaluating the use of radioprotective agents in patients undergoing radioiodine therapy. However, lemon candies, lemon juice and sugarless chewing gum have been proposed to be beneficial for minimizing the side effects of radioiodine within the salivary glands. PMID:23902246

  11. Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies

    PubMed Central

    Leyvraz, S; Herrmann, R; Guillou, L; Honegger, H P; Christinat, A; Fey, M F; Sessa, C; Wernli, M; Cerny, T; Dietrich, D; Pestalozzi, B

    2006-01-01

    Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age <60 years and all except one in good performance status (0 or 1). The chemotherapy treatment consisted of ifosfamide 10 g m−2 (continuous infusion for 5 days), doxorubicin 30 mg m−2 day−1 × 3 (total dose 90 mg m−2), mesna and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A median of 4 (1–6) cycles per patient was administered. Twenty-two patients responded to therapy, including three complete responders and 19 partial responders for an overall response rate of 48% (95% CI: 33–63%). The response rate was not different between localised and metastatic diseases or between histological types, but was higher in grade 3 tumours. Median overall survival was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in 43% of patients and found to be the most significant predictor for favourable survival (exploratory multivariate analysis). Haematological toxicity was severe, including grade ⩾3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies. PMID:17031396

  12. High-dose Daptomycin Therapy for Staphylococcal Endocarditis and When to Apply It

    PubMed Central

    Smith, Jordan R.; Claeys, Kimberly; Barber, Katie E.; Rybak, Michael J.

    2014-01-01

    Infective endocarditis (IE) continues to present a large burden to the healthcare system. Staphylococcus aureus, the leading pathogen associated with the disease, has always proven difficult to treat. Increasing numbers of S. aureus isolates are demonstrating reduced susceptibility to vancomycin, and therapeutic options are limited. Daptomycin is frequently employed when vancomycin therapy proves unsuccessful or when vancomycin MIC values rise above 1 mg/L. Currently, daptomycin is FDA-approved at a dose of 6 mg/kg/day for the treatment of S. aureus bacteremia and associated right-sided endocarditis. However, numerous in vitro and clinical studies suggest that daptomycin doses up to 12 mg/kg/day may provide improved efficacy and resistance prevention. Additionally, high-dose daptomycin has demonstrated excellent safety. Together, these data suggest a role for high-dose daptomycin in staphylococcal IE patients who are severely ill, previously failed therapy with vancomycin, or possess a S. aureus isolate with an elevated vancomycin MIC. PMID:25165017

  13. High-dose MVCT image guidance for stereotactic body radiation therapy

    SciTech Connect

    Westerly, David C.; Schefter, Tracey E.; Kavanagh, Brian D.; Chao, Edward; Lucas, Dan; Flynn, Ryan T.; Miften, Moyed

    2012-08-15

    Purpose: Stereotactic body radiation therapy (SBRT) is a potent treatment for early stage primary and limited metastatic disease. Accurate tumor localization is essential to administer SBRT safely and effectively. Tomotherapy combines helical IMRT with onboard megavoltage CT (MVCT) imaging and is well suited for SBRT; however, MVCT results in reduced soft tissue contrast and increased image noise compared with kilovoltage CT. The goal of this work was to investigate the use of increased imaging doses on a clinical tomotherapy machine to improve image quality for SBRT image guidance. Methods: Two nonstandard, high-dose imaging modes were created on a tomotherapy machine by increasing the linear accelerator (LINAC) pulse rate from the nominal setting of 80 Hz, to 160 Hz and 300 Hz, respectively. Weighted CT dose indexes (wCTDIs) were measured for the standard, medium, and high-dose modes in a 30 cm solid water phantom using a calibrated A1SL ion chamber. Image quality was assessed from scans of a customized image quality phantom. Metrics evaluated include: contrast-to-noise ratios (CNRs), high-contrast spatial resolution, image uniformity, and percent image noise. In addition, two patients receiving SBRT were localized using high-dose MVCT scans. Raw detector data collected after each scan were used to reconstruct standard-dose images for comparison. Results: MVCT scans acquired using a pitch of 1.0 resulted in wCTDI values of 2.2, 4.7, and 8.5 cGy for the standard, medium, and high-dose modes respectively. CNR values for both low and high-contrast materials were found to increase with the square root of dose. Axial high-contrast spatial resolution was comparable for all imaging modes at 0.5 lp/mm. Image uniformity was improved and percent noise decreased as the imaging dose increased. Similar improvements in image quality were observed in patient images, with decreases in image noise being the most notable. Conclusions: High-dose imaging modes are made possible on a

  14. [Procedure guidelines for radioiodine therapy of differentiated thyroid cancer. Version 4].

    PubMed

    Dietlein, Markus; Eschner, Wolfgang; Grünwald, Frank; Lassmann, Michael; Verburg, Frederik A; Luster, Markus

    2016-06-28

    The procedure guideline for radioiodine therapy of differentiated thyroid cancer (version 4) was developed in the consensus of a representative expert group. This fulfils the level S1 (first step) within the AWMF classification of Clinical Practice Guidelines (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, Germany). This procedure guideline completed the guideline for surgical management of thyroid cancer (level S2) with the aspects from nuclear medicine. Controversies over ablative radioiodine therapy in small papillary thyroid cancers and in minimally invasive follicular cancer without angioinvasion, over empirical standard doses for ablative radioiodine therapy, and over the kind of TSH-stimulation were described and the guideline formulated a corridor of good clinical practice. The text has included the recent results from the National Cancer database and the SEER database (both from the USA), indicating that the ablative radioiodine therapy has improved the survival rate even in low risk patients. Such a statistically significant benefit can be detected only by a national cancer registry with long-term follow-up data. PMID:27350004

  15. High-dose statin therapy and risk of intracerebral hemorrhage: a meta-analysis.

    PubMed

    Pandit, A K; Kumar, P; Kumar, A; Chakravarty, K; Misra, S; Prasad, K

    2016-07-01

    Statin plays a major role in the primary and secondary prevention of cardiovascular disease (CVD). Inconsistent findings in the studies have been observed toward the risk of intracerebral hemorrhage (ICH) using higher dose of statin. To examine this issue, we performed a meta-analysis of randomized controlled trials (RCTs) to assess the association between higher dose of various statins and risk of ICH among patients with CVD. Literature was searched for studies published before June 10, 2015, using electronic database 'PubMed', 'EMBASE', and 'Google Scholar' as well as from many trial databases. The following search terms were used: 'Statin therapy' AND 'Cardiovascular Disease', AND 'Dose' AND 'Intracerebral hemorrhage', AND 'Randomized Controlled Trials' AND 'High Dose Statin'. High dose of statins was defined as atorvastatin 80 mg, simvastatin 80 mg, pravastatin 40 mg, rosuvastatin 20 mg per day. Fixed-effect model was used to estimate the risk ratio (RR) and 95% confidence interval (CI) if heterogeneity was <50%; otherwise, random-effect model was used. Begg's funnel plot was used to assess the publication bias. Seven RCTs involving 31,099 subjects receiving high-dose statin and 31,105 subjects receiving placebo were analyzed in our meta-analysis. A significant risk of ICH was observed in subjects with higher dose of statin (RR = 1.53; 95% CI: 1.16-2.01; P = 0.002). There was no difference in all-cause mortality between the two groups (RR = 0.95; 95% CI: 0.86-1.06; P = 0.36). No publication bias was observed through Begg's funnel plot. Higher dose of statins was found to be associated with the risk of ICH. Future studies are needed to confirm these findings. PMID:26647879

  16. Influence of prophylactic anticonvulsant therapy on high-dose busulphan kinetics.

    PubMed

    Hassan, M; Oberg, G; Björkholm, M; Wallin, I; Lindgren, M

    1993-01-01

    The pharmacokinetics of high-dose busulphan was studied in 17 patients during conditioning prior to bone marrow transplantation using deuterium-labeled busulphan (d8-BU). About 50% of busulphan doses 1 and 16 was replaced with d8-BU. Patients were treated with phenytoin or diazepam as prophylactic anticonvulsant therapy. Patients who received phenytoin demonstrated significantly higher clearance (mean +/- SD, 3.32 +/- 0.99 ml min-1 kg-1), a lower area under the concentration-time curve (AUC, 5,412 +/- 1,534 ng h ml-1; corrected for dose/kilogram) and a shorter elimination half-life (3.03 +/- 0.57 h) for the last dose of d8-BU (dose 16) as compared with the first dose (2.80 +/- 0.78 ml min-1 kg-1, 6,475 +/- 2,223 ng h ml-1 and 3.94 +/- 1.10 h, respectively). No difference in the above mentioned pharmacokinetic parameters was seen in patients treated with diazepam. Moreover, a continuous decrease in the steady-state level of busulphan was observed in four of seven patients in the phenytoin-treated group, whereas in the diazepam group, such a decrease was seen in only one of eight patients. We conclude that phenytoin used as prophylactic anticonvulsant therapy alters busulphan pharmacokinetics and, most probably, its pharmacodynamics. For adequate prophylactic therapy, anticonvulsants with fewer enzyme-inductive properties than phenytoin should be used. PMID:8269597

  17. Use of corticosteroids to prevent progression of Graves' ophthalmopathy after radioiodine therapy for hyperthyroidism

    SciTech Connect

    Bartalena, L.; Marcocci, C.; Bogazzi, F.; Panicucci, M.; Lepri, A.; Pinchera, A. )

    1989-11-16

    We studied the effects of radioiodine treatment of hyperthyroidism due to Graves' disease on Graves' ophthalmopathy and the possible protective role of corticosteroids. Between June 1985 and June 1988, 26 patients were randomly assigned to treatment with radioiodine alone (group 1) and 26 to treatment with this agent and concomitant administration of systemic prednisone for four months (group 2). The initial dose of prednisone was 0.4 to 0.5 mg per kilogram of body weight for one month; the drug was gradually withdrawn over the next three months. All patients were evaluated at 3-month intervals for 18 months after they underwent radioiodine therapy. Ocular changes were assessed with the ophthalmopathy index; patients with moderate-to-severe changes (scores greater than or equal to 4) were excluded from the study. Before treatment, 10 patients in group 1 and 5 in group 2 had no evidence of ophthalmopathy: in none of them did ocular symptoms appear after radioiodine therapy. Among the patients in group 1 with an initial ophthalmopathy index greater than or equal to 1, ocular disease worsened in 56 percent (mostly involving soft-tissue changes and extraocular-muscle function) and did not change in 44 percent. In contrast, ophthalmopathy improved in 52 percent and did not change in 48 percent of group 2. The mean ophthalmopathy index increased from 1.5 to 3.0 in group 1 (P less than 0.005) and decreased from 2.2 to 1.3 in group 2 (P less than 0.05). We conclude that systemic corticosteroid treatment prevents the exacerbations of Graves' ophthalmopathy that occur after radioiodine therapy in a substantial proportion of patients with hyperthyroidism who have some degree of ocular involvement before treatment.

  18. High Dose Simvastatin Exhibits Enhanced Lipid Lowering Effects Relative to Simvastatin/Ezetimibe Combination Therapy

    PubMed Central

    Settergren, Magnus; D'Alexandri, Fabio Luiz; Haeggström, Jesper Z.; Fiehn, Oliver; Hyötyläinen, Tuulia; Pedersen, Theresa L.; Newman, John W.; Orešič, Matej; Pernow, John; Wheelock, Craig E.

    2014-01-01

    Statins are the frontline in cholesterol reduction therapies; however use in combination with agents that possess complimentary mechanisms of action may achieve further reductions in LDL-C. Thirty-nine patients were treated with either 80mg simvastatin (n=20) or 10mg simvastatin plus 10mg ezetimibe (n=19) for 6 weeks. Dosing was designed to produce comparable LDL-C reductions, while enabling assessment of potential simvastatin-associated pleiotropic effects. Baseline and post-treatment plasma were analyzed for lipid mediators (e.g., eicosanoids, endocannabinoids) and structural lipids by liquid chromatography tandem mass spectrometry. Following statistical analysis and orthogonal projections to latent structures (OPLS) multivariate modeling, no changes were observed in lipid mediator levels, while global structural lipids were reduced in response to both mono- (R2Y=0.74, Q2=0.66, CV-ANOVA p=7.0×10-8) and combination therapy (R2Y=0.67, Q2=0.54, CV-ANOVA p=2.6×10−5). OPLS modeling identified a subset of 12 lipids that classified the two treatment groups after 6 weeks (R2Y=0.65, Q2=0.61, CV-ANOVA p=5.4×10−8). Decreases in the lipid species PC(15:0/18:2) and HexCer(d18:1/24:0) were the strongest discriminators of LDL-C reductions for both treatment groups (q<0.00005), while PE(36:3e) contributed most to distinguishing treatment groups (q=0.017). Shifts in lipid composition were similar for high-dose simvastatin and simvastatin/ezetimibe combination therapy, but the magnitude of the reduction was linked to simvastatin dosage. Simvastatin therapy did not affect circulating levels of lipid mediators, suggesting that pleiotropic effects are not associated with eicosanoid production. Only high-dose simvastatin reduced the relative proportion of sphingomyelin and ceramide to phosphatidylcholine (q=0.008), suggesting a pleiotropic effect previously associated with a reduced risk of cardiovascular disease. PMID:25516625

  19. External beam radiation therapy followed by high-dose-rate brachytherapy for inoperable superficial esophageal carcinoma

    SciTech Connect

    Pasquier, David . E-mail: d-pasquier@o-lambret.fr; Mirabel, Xavier; Adenis, Antoine; Rezvoy, Nicolas; Hecquet, Genevieve; Fournier, Charles; Coche-Dequeant, Bernard; Prevost, Bernard; Castelain, Bernard; Lartigau, Eric

    2006-08-01

    Purpose: The aim of this study was to retrospectively evaluate the feasibility, efficacy, and tolerance of external beam radiotherapy followed by high-dose-rate brachytherapy in inoperable patients with superficial esophageal cancer. Patients and Methods: From November 1992 to May 1999, 66 patients with superficial esophageal cancer were treated with exclusive radiotherapy. The median age was 60 years (range, 41-85). Fifty-three percent of them were ineligible for surgery owing to synchronous or previously treated head-and-neck cancer. Most of the patients (n = 49) were evaluated with endoscopic ultrasonography (EUS) or computed tomography (CT). The mean doses of external beam radiotherapy and high-dose rate brachytherapy were 57.1 Gy ({+-}4.83) and 8.82 Gy ({+-}3.98), respectively. The most frequently used regimen was 60 Gy followed by 7 Gy at 5 mm depth in two applications. Results: Among patients evaluated with EUS or CT, the complete response rate was 98%. The 3-, 5-, and 7-year survival rates were 57.9%, 35.6%, and 26.6%, respectively. Median overall survival was 3.8 years. The 5-year relapse-free survival and cause-specific survival were 54.6% and 76.9%. The 5-year overall, relapse-free, and cause-specific survival of the whole population of 66 patients was 33%, 53%, and 77%, respectively. Local failure occurred in 15 of 66 patients; 6 were treated with brachytherapy. Severe late toxicity (mostly esophageal stenosis) rated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale occurred in 6 of 66 patients (9%). Conclusion: This well tolerated regimen may be a therapeutic alternative for inoperable patients with superficial esophageal cancer. Only a randomized study could be able to check the potential benefit of brachytherapy after external beam radiation in superficial esophageal cancer.

  20. Radioiodine therapy in patients with hyperthyroid disorder: standard versus dosimetric activity application.

    PubMed

    Reinartz, P; Zimny, M; Schaefer, W; Mueller, B; Buell, U; Sabri, O

    2003-12-01

    Due to its high success rate and non-invasive character, an increasing demand for radioiodine therapy can be seen. This study was conducted to determine whether standardized 131I activities can be used to facilitate management of patients with hyperthyroid disorder or whether a pre-therapeutic radioiodine test is advisable to determine an adequate therapeutic activity. The therapeutic uptake of 218 patients with benign thyroid disorders were determined and compared with 24 h and 48 h test uptake measurements as well as with calculated standard uptake values. Since there is a linear relationship between iodine uptake and delivered radiation dose, the effect of the different therapeutic approaches on the latter parameter was analysed. Special care was taken to assess possible differences between the various thyroid disorders. A mean deviation between pre-therapeutic test uptake and actual therapeutic uptake of 14.7% was observed in contrast to one of 29.1% when using disease specific standard values per millilitre of thyroid tissue. Furthermore, the proportion of patients with large deviations of more than 40% increased drastically when using standard uptake values (with radioiodine test, 4.1%; with standard values, 18.8%). In conclusion, the dosimetric approach with a pre-therapeutic radioiodine test proved to be the most accurate therapeutic procedure. Both the 24 h and 48 h test uptake measurements gave analogous results and yielded a correlation coefficient of 0.91 when compared with the therapeutic uptake. While it may be tempting to use standard activities to facilitate patient management, the findings of this study confirm that, for precise therapy planning, a pre-therapeutic radioiodine test is advised. Since no significant difference could be found between the 24 h and 48 h test uptake values, an early measurement 24 h after administration of the test activity is recommended. PMID:14627852

  1. Radioiodine Therapy Does Not Change the Atherosclerotic Burden of the Carotid Arteries

    PubMed Central

    Andersen, Ulrik Bjørn; Sørensen, Christian Hjort; Nygaard, Birte; Jensen, Lars Thorbjørn

    2016-01-01

    Background and aim: Atherosclerosis evolves or accelerates when arteries are exposed to ionizing radiation, both early and late after exposure. Radioiodine therapy of benign thyroid disease exposes the carotid arteries to 4–50 Gy, and may thereby increase the risk of atherosclerosis. Increased risk of cerebrovascular events has been reported after radioiodine therapy. This study aimed to examine whether atherosclerosis develops early or late after radioiodine therapy of benign thyroid disease. Method: Patients treated for benign thyroid disorders (nontoxic goiter, adenoma, and hyperthyroidism) were examined with ultrasound for the main outcome, carotid intima media thickness (CIMT), and for plaque presence (plaque presence only in late damage). Signs of early damage from radioiodine were studied in 39 radioiodine-treated patients, who were examined before treatment and at 1, 3, 6, and 12 months after treatment. Late changes were studied in a cross-sectional case-control design, with radioiodine-treated patients as cases (n = 193) and patients treated with surgery as controls (n = 95). Data were analyzed with repeated measurement for longitudinal data, and with multivariate regression for cross-sectional data. Results were adjusted for age, sex, cholesterol, smoking status, known atherosclerotic disease, and body mass index. Results: No changes in CIMT were found in the patients followed prospectively for one year after treatment with radioactive iodine for benign thyroid disease (p = 0.58). In the study on late effects, there was no difference in CIMT (p = 0.25) or presence of plaques (p = 0.70) between those treated with radioactive iodine and those treated with surgery (9.8 and 5.6 years since treatment, respectively). Furthermore, the level of thyrotropin (TSH) did not influence these atherosclerosis markers. Conclusion: No early changes in CIMT were detected in patients treated with radioactive iodine for benign thyroid disease. No signs

  2. Is High Dose Therapy Superior to Conventional Dose Therapy as Initial Treatment for Relapsed Germ Cell Tumors? The TIGER Trial

    PubMed Central

    Feldman, Darren R.; Huddart, Robert; Hall, Emma; Beyer, Jörg; Powles, Thomas

    2011-01-01

    Metastatic germ cell tumours (GCTs) are usually cured with cisplatin based chemotherapy and standard treatment algorithms are established. However when this treatment fails and the disease relapses, standard treatment is much more uncertain. Both conventional dose therapy (CDT) and high dose therapy (HDT) are widely used, due to the lack of conclusive data supporting one specific approach. A recent retrospective analysis focusing on this population suggested a significant benefit for HDT. Retrospective analyses are prone to bias, and therefore while this data is provocative it is by no mean conclusive. For this reason the international community is supporting a prospective randomised trial in this area comparing CDT(TIP) with sequential HDT (TICE). The planned open labelled randomised phase III study (TIGER) is due to open in 2011 and will recruit 390 patients to detect a 13% difference in 2 year progression free survival (primary endpoint). It is hoped that this large study will conclusively resolve the uncertainty which currently exists. PMID:21750688

  3. Cardiovascular Safety Profile and Clinical Experience With High-Dose Domperidone Therapy for Nausea and Vomiting

    PubMed Central

    Ortiz, Arleen; Cooper, Chad J.; Alvarez, Alicia; Gomez, Yvette; Sarosiek, Irene

    2015-01-01

    Abstract: Introduction: Domperidone is a dopamine receptor antagonist with peripheral prokinetic and central antiemetic properties. Prolongation of the QTc interval with chronic use of oral domperidone in standard doses has been reported in the literature. Our goal was to investigate cardiac toxicity in patients receiving 2-fold greater doses than in previous reports. Methods: A retrospective chart review was conducted of patients with nausea (N) and vomiting (V) receiving domperidone from 2009 to 2013 under an Investigational New Drug (IND) protocol. Patient demographics, indications for therapy, clinical outcomes, cardiac symptoms and electrocardiogram tracings were reviewed. Prolonged QTc was verified if >470 milliseconds in females (F) and >450 milliseconds in males (M). Results: A total of 64 patients, 44 female (37% Hispanic, 60% white, 3% African American), were taking domperidone for diabetic gastroparesis 45%; idiopathic gastroparesis 36%; chronic N&V 8%; dumping syndrome 5%; cyclic vomiting 5% and conditioned vomiting 1%. Mean duration of therapy was 8 months (range, 3 months to 4 years). Doses ranged from 40 to 120 mg/d with 90% receiving 80 to 120 mg compared with the standard dose of 40 mg. Of note, 73% of subjects benefited from treatment with reduced nausea and vomiting. Thirty-seven patients had follow-up electrocardiograms available, and they showed that the mean QTc at baseline was 424 milliseconds ± 28.4 (SD) compared with 435 milliseconds ± 27.2 (SD) at follow-up (not significant). Ten of these patients had prolonged QTc at F/U ranging from 453 to 509 milliseconds, without any cardiovascular complaints. There was no relationship between prolonged QTc and daily dose of domperidone, body mass index or age. Conclusions: Our data indicate that at very high dosing, the prokinetic/antiemetic agent domperidone has a low risk of adverse cardiovascular events while exhibiting good clinical efficacy. PMID:25828198

  4. High-Dose-Rate Intraoperative Radiation Therapy for Recurrent Head-and-Neck Cancer

    SciTech Connect

    Perry, David J.; Chan, Kelvin; Wolden, Suzanne; Zelefsky, Michael J.; Chiu, Johnny; Cohen, Gilad; Zaider, Marco; Kraus, Dennis; Shah, Jatin; Lee, Nancy

    2010-03-15

    Purpose: To report the use of high-dose-rate intraoperative radiation therapy (HDR-IORT) for recurrent head-and-neck cancer (HNC) at a single institution. Methods and Materials: Between July 1998 and February 2007, 34 patients with recurrent HNC received 38 HDR-IORT treatments using a Harrison-Anderson-Mick applicator with Iridium-192. A single fraction (median, 15 Gy; range, 10-20 Gy) was delivered intraoperatively after surgical resection to the region considered at risk for close or positive margins. In all patients, the target region was previously treated with external beam radiation therapy (median dose, 63 Gy; range, 24-74 Gy). The 1- and 2-year estimates for in-field local progression-free survival (LPFS), locoregional progression-free survival (LRPFS), distant metastases-free survival (DMFS), and overall survival (OS) were calculated. Results: With a median follow-up for surviving patients of 23 months (range, 6-54 months), 8 patients (24%) are alive and without evidence of disease. The 1- and 2-year LPFS rates are 66% and 56%, respectively, with 13 (34%) in-field recurrences. The 1- and 2-year DMFS rates are 81% and 62%, respectively, with 10 patients (29%) developing distant failure. The 1- and 2-year OS rates are 73% and 55%, respectively, with a median time to OS of 24 months. Severe complications included cellulitis (5 patients), fistula or wound complications (3 patients), osteoradionecrosis (1 patient), and radiation-induced trigeminal neuralgia (1 patient). Conclusions: HDR-IORT has shown encouraging local control outcomes in patients with recurrent HNC with acceptable rates of treatment-related morbidity. Longer follow-up with a larger cohort of patients is needed to fully assess the benefit of this procedure.

  5. Evaluation of high-dose daptomycin for therapy of experimental Staphylococcus aureus foreign body infection

    PubMed Central

    Schaad, Heinz J; Bento, Manuela; Lew, Daniel P; Vaudaux, Pierre

    2006-01-01

    Background Daptomycin is a novel cyclic lipopeptide whose bactericidal activity is not affected by current antibiotic resistance mechanisms displayed by S. aureus clinical isolates. This study reports the therapeutic activity of high-dose daptomycin compared to standard regimens of oxacillin and vancomycin in a difficult-to-treat, rat tissue cage model of experimental therapy of chronic S. aureus foreign body infection. Methods The methicillin-susceptible S. aureus (MSSA) strain I20 is a clinical isolate from catheter-related sepsis. MICs, MBCs, and time-kill curves of each antibiotic were evaluated as recommended by NCCLS, including supplementation with physiological levels (50 mg/L) of Ca2+ for daptomycin. Two weeks after local infection of subcutaneously implanted tissue cages with MSSA I20, each animal received (i.p.) twice-daily doses of daptomycin, oxacillin, or vancomycin for 7 days, or was left untreated. The reductions of CFU counts in each treatment group were analysed by ANOVA and Newman-Keuls multiple comparisons procedures. Results The MICs and MBCs of daptomycin, oxacillin, or vancomycin for MSSA strain I20 were 0.5 and 1, 0.5 and 1, or 1 and 2 mg/L, respectively. In vitro elimination of strain I20 was more rapid with 8 mg/L of daptomycin compared to oxacillin or vancomycin. Twice-daily administered daptomycin (30 mg/kg), oxacillin (200 mg/kg), or vancomycin (50 mg/kg vancomycin) yielded bactericidal antibiotic levels in infected cage fluids throughout therapy. Before therapy, mean (± SEM) viable counts of strain I20 were 6.68 ± 0.10 log10 CFU/mL of cage fluid (n = 74). After 7 days of therapy, the mean (± SEM) reduction in viable counts of MSSA I20 was 2.62 (± 0.30) log10 CFU/mL in cages (n = 18) of daptomycin-treated rats, exceeding by >2-fold (P < 0.01) the viable count reductions of 0.92 (± 0.23; n = 19) and 0.96 (± 0.24; n = 18) log10 CFU/mL in cages of oxacillin-treated and vancomycin-treated rats, respectively. Viable counts in cage

  6. Short and long-term effects of high-dose intravenous methylprednisolone pulse therapy on thyroid-associated ophthalmopathy

    PubMed Central

    Liu, Xiaomei; Wang, Shu; Qin, Li; Qiang, Wei; Dahal, Mahesh; Fan, Ping; Gao, Shan; Shi, Bingyin

    2016-01-01

    The majority of previous studies on high-dose intravenous methylprednisolone pulse (IVMP) therapy have observed the clinical conditions of patients prior to and following treatment without any long-term follow-up, and these studies have predominantly focused on combined treatment. The present prospective clinical study aimed to assess the long-term effects and safety of high-dose IVMP therapy in thyroid-associated ophthalmopathy (TAO), as well as the significance of thyrotropin receptor antibody (TRAb) and soluble intercellular adhesion molecule-l (sICAM-1) during IVMP therapy. A total of 58 patients with TAO were treated with high-dose IVMP therapy, and their clinical characteristics and indices were recorded before, during and after therapy, with a 12–57 month (mean, 28.4 months) follow-up. Before treatment and on the second day after each IVMP therapy, serum TRAb and sICAM-1 levels were evaluated in 23 patients with TAO via a competitive radioimmunoassay and enzyme-linked immunosorbent assay, respectively. The results of the present study demonstrated that the symptoms of eyelid swelling, ophthalmodynia, photophobia, lacrimation and diplopia, and visual acuity, ocular motility, proptosis and clinical activity score (CAS) indices were all significantly improved after IVMP therapy. In addition, analysis of covariance demonstrated that alterations in the levels of serum TRAb during the course of treatment were associated with CAS of TAO, whereas the change in serum sICAM-1 was not. In conclusion, high-dose IVMP therapy is an effective, safe, stable and well-tolerated treatment for TAO, which is associated with rare, minor adverse effects. Furthermore, serum TRAb levels are correlated with the CAS of TAO and may serve as a predictor of the response to methylprednisolone therapy. PMID:27446294

  7. Pretreatment with betamethasone of patients with Graves' disease given radioiodine therapy: thyroid autoantibody responses and outcome of therapy

    SciTech Connect

    Gamstedt, A.; Karlsson, A. )

    1991-07-01

    The effects of betamethasone on thyroid autoantibody responses and outcome of radioiodine therapy were determined over a period of 1 yr in a prospective randomized study of 40 patients with Graves' disease. Twenty patients were given placebo tablets, and 20 patients were treated with betamethasone from 3 weeks before until 4 weeks after {sup 131}I therapy. At the time of inclusion in the study, the mean serum concentrations of TSH receptor antibodies, thyroid peroxidase antibodies, and thyroglobulin antibodies (TgAb) were increased in both groups. Three weeks of treatment with betamethasone reduced the thyroid peroxidase antibody and TgAb titers as well as the serum concentrations of thyroid hormones. A decrease in the TSH receptor antibody level was not statistically significant. After radioiodine therapy, transient increases in thyroid autoantibody levels were observed. The titers of the different antibodies generally changed in parallel. In some patients a detectable level of a given antibody was found only after the radioiodine treatment, and in two cases, TgAb did not appear at all, although the two other antibodies increased temporarily. Betamethasone delayed, but did not abolish, the {sup 131}I-induced antibody peaks. Betamethasone also caused a reduction in the total serum immunoglobulin G, a reduction which persisted throughout the study period. When the study ended, 17 patients given placebo and 9 patients given betamethasone were receiving replacement therapy due to the development of hypothyroidism. These patients at this point in time had lower antibody levels than those not requiring T4. The results of this study demonstrate that betamethasone reduces and modifies the thyroid autoantibody responses as well as the outcome of radioiodine therapy in patients with Graves' disease.

  8. Focal takotsubo cardiomyopathy with high-dose interleukin-2 therapy for malignant melanoma.

    PubMed

    Damodaran, Senthil; Mrozek, Ewa; Liebner, David; Kendra, Kari

    2014-12-01

    High-dose interleukin-2 (IL-2) is an available treatment option for patients with metastatic melanoma or renal cell carcinoma, and is associated with sustained complete and partial responses in a subset of patients. IL-2, however, is not devoid of toxicities, most of which involve the cardiovascular system and manifest as hypotension, arrhythmias, and cardiomyopathy. This report describes an unusual presentation of takotsubo cardiomyopathy in a postmenopausal woman receiving high-dose IL-2 for metastatic melanoma. PMID:25505207

  9. Optically erasable samarium-doped fluorophosphate glasses for high-dose measurements in microbeam radiation therapy

    NASA Astrophysics Data System (ADS)

    Morrell, B.; Okada, G.; Vahedi, S.; Koughia, C.; Edgar, A.; Varoy, C.; Belev, G.; Wysokinski, T.; Chapman, D.; Sammynaiken, R.; Kasap, S. O.

    2014-02-01

    Previous work has demonstrated that fluorophosphate (FP) glasses doped with trivalent samarium (Sm3+) can be used as a dosimetric detector in microbeam radiation therapy (MRT) to measure high radiation doses and large dose variations with a resolution in the micrometer range. The present work addresses the use of intense optical radiation at 405 nm to erase the recorded dose information in Sm3+-doped FP glass plates and examines the underlying physics. We have evaluated both the conversion and optical erasure of Sm3+-doped FP glasses using synchrotron-generated high-dose x-rays at the Canadian Light Source. The Sm-ion valency conversion is accompanied by the appearance of x-ray induced optical absorbance due to the trapping of holes and electrons into phosphorus-oxygen hole (POHC) and electron (POEC) capture centers. Nearly complete Sm2+ to Sm3+ reconversion (erasure) may be achieved by intense optical illumination. Combined analysis of absorbance and electron spin resonance measurements indicates that the optical illumination causes partial disappearance of the POHC and the appearance of new POEC. The suggested model for the observed phenomena is based on the release of electrons during the Sm2+ to Sm3+ reconversion process, the capture of these electrons by POHC (and hence their disappearance), or by PO groups, with the appearance of new and/or additional POEC. Optical erasure may be used as a practical means to erase the recorded data and permits the reuse of these Sm-doped FP glasses in monitoring dose in MRT.

  10. Optically erasable samarium-doped fluorophosphate glasses for high-dose measurements in microbeam radiation therapy

    SciTech Connect

    Morrell, B.; Okada, G.; Vahedi, S.; Koughia, C. Kasap, S. O.; Edgar, A.; Varoy, C.; Belev, G.; Wysokinski, T.; Chapman, D.; Sammynaiken, R.

    2014-02-14

    Previous work has demonstrated that fluorophosphate (FP) glasses doped with trivalent samarium (Sm{sup 3+}) can be used as a dosimetric detector in microbeam radiation therapy (MRT) to measure high radiation doses and large dose variations with a resolution in the micrometer range. The present work addresses the use of intense optical radiation at 405 nm to erase the recorded dose information in Sm{sup 3+}-doped FP glass plates and examines the underlying physics. We have evaluated both the conversion and optical erasure of Sm{sup 3+}-doped FP glasses using synchrotron-generated high-dose x-rays at the Canadian Light Source. The Sm-ion valency conversion is accompanied by the appearance of x-ray induced optical absorbance due to the trapping of holes and electrons into phosphorus-oxygen hole (POHC) and electron (POEC) capture centers. Nearly complete Sm{sup 2+} to Sm{sup 3+} reconversion (erasure) may be achieved by intense optical illumination. Combined analysis of absorbance and electron spin resonance measurements indicates that the optical illumination causes partial disappearance of the POHC and the appearance of new POEC. The suggested model for the observed phenomena is based on the release of electrons during the Sm{sup 2+} to Sm{sup 3+} reconversion process, the capture of these electrons by POHC (and hence their disappearance), or by PO groups, with the appearance of new and/or additional POEC. Optical erasure may be used as a practical means to erase the recorded data and permits the reuse of these Sm-doped FP glasses in monitoring dose in MRT.

  11. Treatment results of high dose cabergoline as an adjuvant therapy in six patients with established severe ovarian hyper stimulation syndrome

    PubMed Central

    Saharkhiz, Nasrin; Akbari Sene, Azadeh; Salehpour, Saghar; Tamimi, Maryam; Vasheghani Farahani, Masoumeh; Sheibani, Kourosh

    2014-01-01

    Background: The beneficial role of cabergoline as a prophylactic agent to prevent ovarian hyper stimulation syndrome (OHSS) among high-risk patients has been demonstrated in previous studies. But data for its role as a treatment for established severe OHSS is still limited. We represent the treatment results of high dose oral cabergoline in management of six patients after the syndrome is established. Case: High-dose oral cabergoline (1 mg daily for eight days) was prescribed as an adjuvant to symptomatic treatment for six hospitalized patients with established severe OHSS following infertility treatment cycles. In two cases OHSS resolved rapidly despite the occurrence of ongoing pregnancy. Conclusion: Considering the treatment outcomes of our patients, high dose cabergoline did not eliminate the need for traditional treatments, but it was a relatively effective and safe therapy in management of established severe OHSS, and prevented the increase in its severity following the occurrence of pregnancy. PMID:25469130

  12. High-dose esomeprazole and amoxicillin dual therapy for first-line Helicobacter pylori eradication: a proof of concept study

    PubMed Central

    Zullo, Angelo; Ridola, Lorenzo; Francesco, Vincenzo De; Gatta, Luigi; Hassan, Cesare; Alvaro, Domenico; Bellesia, Annamaria; de Nucci, Germana; Manes, Gianpiero

    2015-01-01

    Background The prevalence of resistance to clarithromycin and metronidazole has considerably increased, with a corresponding decrease in the eradication rate for Helicobacter pylori (H. pylori) infection. Primary resistance to amoxicillin is extremely low, and esomeprazole was found to exert a noteworthy antimicrobial activity in vitro against H. pylori. A dual therapy with high-dose of esomeprazole coupled with high-dose amoxicillin might be therefore an ideal first-line treatment for H. pylori eradication. We aimed to assess the efficacy of a first-line 10-day, high-dose dual therapy consisting of amoxicillin and esomeprazole to eradicate H. pylori infection. Methods Consecutive naïve H. pylori-infected patients, who underwent an upper endoscopy in 4 Italian hospitals due to dyspeptic symptoms and found to be infected at routine histological assessment, were invited to participate. Patients enrolled received a 10-day, high-dose dual therapy comprising esomeprazole (40 mg t.i.d) and amoxicillin (1 g t.i.d.). At least 4 weeks after the end of the treatment a 13C-urea breath test was performed to evaluate the eradication. Results A total of 56 patients agreed to participate in the study and were all followed-up. The overall eradication was 87.5% (95% CI=78.8•96.2), without a statistically significant difference among centres. Overall, 5 (8.9%; 1.5•16.4%) patients complained of side-effects. Conclusions The 10-day, high-dose dual therapy with esomeprazole and amoxicillin might be an effective and safe first-line regimen. The efficacy of a longer 14-day regimen should be tested. PMID:26423014

  13. Psychiatric side effects of acute high-dose corticosteroid therapy in neurological conditions.

    PubMed

    Lotan, Itay; Fireman, Liora; Benninger, Felix; Weizman, Abraham; Steiner, Israel

    2016-07-01

    It has been implied that high-dose corticosteroids (CSs) commonly cause psychiatric side effects. Here, we examined the rate and risk factors of psychiatric side effects during high-dose CS treatment in patients with neurological disorders. Patients treated with high-dose intravenous CSs for neurological disorders were evaluated for depression, mania, and psychosis using the Beck Depression Inventory, the Geriatric Depression Scale, the Young Mania Rating Scale, and the Brief Psychiatric Rating Scale before CS treatment, immediately after, and 1 month following treatment. Forty-nine consecutive patients were monitored. There was a reduction in the Beck Depression Inventory and Geriatric Depression Scale scores as well as in the Brief Psychiatric Rating Scale scores throughout the study period and a transitory increase in the Young Mania Rating Scale score immediately after CS administration. Thus, a tendency to develop transient mild euphoria during high-dose CS treatment exists, but is reversible at 1 month, whereas a reduction in depressive symptoms tended to persist. Overall, our data indicate that high-dose CS treatment for neurological diseases is relatively safe with respect to psychiatric complications. PMID:26938038

  14. Nebuhaler or nebulizer for high dose bronchodilator therapy in chronic bronchitis: a comparison.

    PubMed

    Allen, M B; Pugh, J; Wilson, R S

    1988-10-01

    We have compared the clinical efficacy of high dose terbutaline sulphate (10 mg four times daily) delivered by either a Nebuhaler or jet nebulizer in 13 patients with chronic bronchitis in a 2-week, open, crossover study. Both treatment regimens improved run-in symptom scores but no significant changes were recorded in peak flow and spirometry. Side-effects were more common with the Nebuhaler and more patients preferred the nebulizer. However, the Nebuhaler is an alternative therapeutic option for delivery of high doses of bronchodilators in patients with chronic bronchitis. PMID:3076792

  15. High-Dose Adjuvant Radiotherapy After Radical Prostatectomy With or Without Androgen Deprivation Therapy

    SciTech Connect

    Ost, Piet; Cozzarini, Cesare; De Meerleer, Gert; Fiorino, Claudio; De Potter, Bruno; Briganti, Alberto; Nagler, Evi V.T.; Montorsi, Francesco; Fonteyne, Valerie; Di Muzio, Nadia

    2012-07-01

    Purpose: To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Methods and Materials: Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was left at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification. Results: After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT. Conclusions: This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.

  16. Graves Disease Induced by Radioiodine Therapy for Toxic Nodular Goiter: A Case Report

    PubMed Central

    Yürekli, Yakup; Cengiz, Arzu; Güney, Engin

    2015-01-01

    Graves’ disease (GD) may be observed as an infrequent adverse effect after radioiodine therapy (RAIT) for toxic thyroid adenoma (TA) and toxic multi nodular goiter (MNG). We present a case of a 55-year-old male with a toxic nodule who was treated with RAI. After therapy, the patient’s serum free triiodothyronine (fT3) and free thyroxine (fT4) levels gradually increased. Antithyroid peroxidase (TPOAb), antithyroglobulin (TgAb) and TSH-receptor antibodies (TRAb) were also positive. Thyroid scintigraphy revealed diffuse intense uptake after four months of RAIT. Radiation-induced GD should be considered in patients with aggravated hyperthyroidism 3-4 months after therapy.

  17. Graves Disease Induced by Radioiodine Therapy for Toxic Nodular Goiter: A Case Report.

    PubMed

    Yürekli, Yakup; Cengiz, Arzu; Güney, Engin

    2015-10-01

    Graves' disease (GD) may be observed as an infrequent adverse effect after radioiodine therapy (RAIT) for toxic thyroid adenoma (TA) and toxic multi nodular goiter (MNG). We present a case of a 55-year-old male with a toxic nodule who was treated with RAI. After therapy, the patient's serum free triiodothyronine (fT3) and free thyroxine (fT4) levels gradually increased. Antithyroid peroxidase (TPOAb), antithyroglobulin (TgAb) and TSH-receptor antibodies (TRAb) were also positive. Thyroid scintigraphy revealed diffuse intense uptake after four months of RAIT. Radiation-induced GD should be considered in patients with aggravated hyperthyroidism 3-4 months after therapy. PMID:27529890

  18. Graves' disease radioiodine-therapy: Choosing target absorbed doses for therapy planning

    SciTech Connect

    Willegaignon, J. Sapienza, M. T.; Coura-Filho, G. B.; Buchpiguel, C. A.; Watanabe, T.; Traino, A. C.

    2014-01-15

    Purpose: The precise determination of organ mass (m{sub th}) and total number of disintegrations within the thyroid gland (A{sup ~}) are essential for thyroid absorbed-dose calculations for radioiodine therapy. Nevertheless, these parameters may vary according to the method employed for their estimation, thus introducing uncertainty in the estimated thyroid absorbed dose and in any dose–response relationship derived using such estimates. In consideration of these points, thyroid absorbed doses for Graves’ disease (GD) treatment planning were calculated using different approaches to estimating the m{sub th} and the A{sup ~}. Methods: Fifty patients were included in the study. Thyroid{sup 131}I uptake measurements were performed at 2, 6, 24, 48, 96, and 220 h postadministration of a tracer activity in order to estimate the effective half-time (T{sub eff}) of {sup 131}I in the thyroid; the thyroid cumulated activity was then estimated using the T{sub eff} thus determined or, alternatively, calculated by numeric integration of the measured time-activity data. Thyroid mass was estimated by ultrasonography (USG) and scintigraphy (SCTG). Absorbed doses were calculated with the OLINDA/EXM software. The relationships between thyroid absorbed dose and therapy response were evaluated at 3 months and 1 year after therapy. Results: The average ratio (±1 standard deviation) betweenm{sub th} estimated by SCTG and USG was 1.74 (±0.64) and that between A{sup ~} obtained by T{sub eff} and the integration of measured activity in the gland was 1.71 (±0.14). These differences affect the calculated absorbed dose. Overall, therapeutic success, corresponding to induction of durable hypothyroidism or euthyroidism, was achieved in 72% of all patients at 3 months and in 90% at 1 year. A therapeutic success rate of at least 95% was found in the group of patients receiving doses of 200 Gy (p = 0.0483) and 330 Gy (p = 0.0131) when m{sub th} was measured by either USG or SCTG and A

  19. Repeated high-dose chemotherapy followed by purged autologous bone marrow transplantation as consolidation therapy in metastatic neuroblastoma.

    PubMed

    Hartmann, O; Benhamou, E; Beaujean, F; Kalifa, C; Lejars, O; Patte, C; Behard, C; Flamant, F; Thyss, A; Deville, A

    1987-08-01

    Among 62 children over 1 year of age at diagnosis, who were treated for stage IV neuroblastoma, 33 entered complete remission (CR) or good partial remission (GPR) after conventional therapy and received high-dose chemotherapy (HDC) with in vitro purged autologous bone marrow transplantation (ABMT) as consolidation therapy. The HDC was a combination of carmustine (BCNU), teniposide (VM-26), and melphalan. Thirty-three patients received one course of this regimen, and 18 received two courses. At present, 16 of the 33 grafted patients are alive in continuous CR, with a median follow-up of 28 months. Toxicity of this regimen was tolerable, principally marked by bone marrow depression and gastrointestinal (GI) tract complications. Four complication-related deaths were observed. Relapse post-ABMT occurred most often in the bone marrow. Under this treatment, actuarial disease-free survival is improved compared with that observed under conventional therapy. PMID:3305792

  20. High-dose therapy with peripheral blood progenitor cell transplantation in low-grade non-Hodgkin's lymphoma.

    PubMed

    Haas, R; Moos, M; Möhle, R; Döhner, H; Witt, B; Goldschmidt, H; Murea, S; Flentje, M; Wannenmacher, M; Hunstein, W

    1996-02-01

    It was the objective of our study to evaluate the efficacy of a sequential high-dose therapy with peripheral blood progenitor cell (PBPC) support in patients with low-grade non-Hodgkin's lymphoma (NHL). Since July 1991, 48 patients (23 male/25 female) with a median age of 43 years (range 26-55) were included in the study. At the time of entry, 28 patients were in first and seven in second or higher remission. Twelve patients had relapse of disease and one patient had tumor progression. PBPC were collected during granulocyte colony-stimulating factor (G-CSF)-enhanced leukocyte recovery following treatment with high-dose cytarabine and mitoxantrone (HAM). A median of two leukaphereses (range 2-7) resulted in 6.9 x 10(6) CD34+ cells/kg (median, range 2.1 x 10(6)-38.8 x 10(6)). A comparison was made between the harvests obtained from patients in first remission and those from patients in second remission, in relapse or progressive disease. Patients mobilized in first remission tended to have a greater collection efficiency for CD34+ cells comprising a significantly greater proportion of more primitive CD34+/Thy-1+ progenitor cells. Conversely, leukapheresis (LP) products collected during first remission contained a significantly smaller proportion of CD34+/CD45RA+ cells and CD34+/c-kit+ cells, subsets which reflect a more differentiated progenitor cell stage. Following high-dose therapy and PBPC autografting, the median time to reach platelets > or = 20 x 10(9)/l and neutrophils > or = 0.5 x 10(9)/l and 12 and 13 days, respectively. Two patients died of treatment-related toxic organ failure. Thirty-nine patients are alive in remission after a median follow-up time of 15 months (range 1-31), while seven patients relapsed between 5 and 29 months post-transplantation. Except for one patient autografted in first remission, the patients with relapse had a history of previous relapse or progressive disease. Since the probability of disease-free survival appears to be related

  1. Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe

    PubMed Central

    Garcia, Maristela Magnavita Oliveira; Varela, Carolina Garcez; Silva, Patricia Fontes; Lima, Paulo Roberto Passos; Góes, Paulo Meira; Rodrigues, Marilia Galeffi; Silva, Maria de Lourdes Lima Souza e; Ladeia, Ana Marice Teixeira; Guimarães, Armênio Costa; Correia, Luis Claudio Lemos

    2016-01-01

    Background The effect of statins on the endothelial function in humans remains under discussion. Particularly, it is still unclear if the improvement in endothelial function is due to a reduction in LDL-cholesterol or to an arterial pleiotropic effect. Objective To test the hypothesis that modulation of the endothelial function promoted by statins is primarily mediated by the degree of reduction in LDL-cholesterol, independent of the dose of statin administered. Methods Randomized clinical trial with two groups of lipid-lowering treatment (16 patients/each) and one placebo group (14 patients). The two active groups were designed to promote a similar degree of reduction in LDL-cholesterol: the first used statin at a high dose (80 mg, simvastatin 80 group) and the second used statin at a low dose (10 mg) associated with ezetimibe (10 mg, simvastatin 10/ezetimibe group) to optimize the hypolipidemic effect. The endothelial function was assessed by flow-mediated vasodilation (FMV) before and 8 weeks after treatment. Results The decrease in LDL-cholesterol was similar between the groups simvastatin 80 and simvastatin 10/ezetimibe (27% ± 31% and 30% ± 29%, respectively, p = 0.75). The simvastatin 80 group presented an increase in FMV from 8.4% ± 4.3% at baseline to 11% ± 4.2% after 8 weeks (p = 0.02). Similarly, the group simvastatin 10/ezetimibe showed improvement in FMV from 7.3% ± 3.9% to 12% ± 4.4% (p = 0.001). The placebo group showed no variation in LDL-cholesterol level or endothelial function. Conclusion The improvement in endothelial function with statin seems to depend more on a reduction in LDL-cholesterol levels, independent of the dose of statin administered, than on pleiotropic mechanisms. PMID:27142792

  2. Endocrine function following high dose proton therapy for tumors of the upper clivus

    SciTech Connect

    Slater, J.D.; Austin-Seymour, M.; Munzenrider, J.; Birnbaum, S.; Carroll, R.; Klibanski, A.; Riskind, P.; Urie, M.; Verhey, L.; Goitein, M.

    1988-09-01

    The endocrine status of patients receiving proton radiation for tumors of the upper clivus was reviewed to evaluate the effect of high dose treatment on the pituitary gland. The fourteen patients had chordomas or low grade chondrosarcomas and were all treated by the same techniques. The median tumor dose was 69.7 Cobalt Gray Equivalent (CGE) with a range from 66.6 to 74.4 CGE. (CGE is used because modulated protons have an RBE of 1.1 compared to 60Co). The daily fraction size was 1.8-2.1 CGE. The median follow-up time is 48 months, ranging from 30 to 68 months. All treatments were planned using a computerized multi-dimensional system with the position of the pituitary outlined on the planning CT scan. Review of the dose distribution indicated that the dose to the pituitary ranged from 60.5 to 72.3 CGE, with a median of 67.6 CGE. One female patient had decreased thyroid and gonadotropin function at the time of diagnosis and has been on hormone replacement since that time. The other three females were all pre-menopausal at the time of radiotherapy. At this time four patients (3 males and 1 female) have developed endocrine abnormalities 14 to 45 months after irradiation. All four had evidence of hypothyroidism and two have also developed corticotropin deficiency. The three males had decreased testosterone levels; the female patient developed amenorrhea and hyperprolactinemia. All four are asymptomatic with ongoing hormone replacement.

  3. The protection conferred by chelation therapy in post-MI diabetics might be replicated by high-dose zinc supplementation.

    PubMed

    McCarty, Mark F; DiNicolantonio, James J

    2015-05-01

    The recent Trial to Assess Chelation Therapy (TACT) study, enrolling subjects who had previously experienced a myocardial infarction, has provided strong evidence that intravenous chelation therapy can markedly reduce risk for mortality and vascular events in diabetics, whereas no discernible benefit was observed in non-diabetics. It has plausibly been suggested that this reflects a role for transition metal ions--iron or copper--in the genesis of advanced glycation end products, key mediators of diabetic complications that can destabilize plaque. Since phlebotomy therapy fails to prevent vascular events in diabetics, we hypothesize that labile copper may be the chief culprit whose removal by chelation mediated the benefit observed in TACT. If so, strategies less time and labor intensive than chelation therapy might provide comparable benefit. A number of recent studies report that the copper-specific orally-active chelator trientine can reduce risk for range of diabetic complications in rodents; a clinical trial with this agent demonstrated some decrease in left ventricular mass in diabetics with ventricular hypertrophy. However, until this agent becomes less expensive, supplementation with high-dose zinc may represent a more feasible alternative. Zinc opposes the absorption and redox activity of copper via induction of the antioxidant protein metallothionein, which binds copper tightly. A great many studies demonstrate that increased expression of metallothionein decreases risk for tissue damage in diabetic rodents, and in some of these studies metallothionein expression was boosted by supplemental zinc. Zinc supplementation also modestly improves glycemic control in type 2 diabetics, and might reduce risk for diabetes by protecting pancreatic beta cells from oxidative stress. A long term study assessing the impact of supplementing diabetics with high-dose zinc, assessing risk for mortality, vascular events, and diabetic complications, may be warranted. Histidine

  4. High dose simvastatin exhibits enhanced lipid lowering effects relative to simvastatin/ezetimibe combination therapy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Technical Abstract: Background: Statins are the frontline in cholesterol reduction therapies; however use in combination with agents that possess complimentary mechanisms of action may achieve further reduce in LDL-C. Methods and Results: Thirty-nine patients were treated with either 80mg simvasta...

  5. High-dose radiation therapy alone by moderate hypofractionation for patients with thoracic esophageal squamous cell carcinoma.

    PubMed

    Oh, Dongryul; Noh, Jae Myoung; Nam, Heerim; Lee, Hyebin; Kim, Tae Gyu; Ahn, Yong Chan

    2016-08-01

    We conducted retrospective analyses to investigate the clinical outcome of thoracic esophageal cancer patients who were treated with high-dose radiation therapy (RT) alone by moderate hypofractionation due to medical unfitness or refusal to receive either surgery or chemo-radiotherapy.Between May 2003 and April 2013, 70 patients were treated with high-dose RT alone with curative aim. The planned total RT dose was 60 Gy in daily 3.0 Gy per fraction. We evaluated the survival outcome, toxicities, and prognostic factors affecting patients' survival.At the time of analysis, 32 patients experienced disease progression. The 2-year overall survival (OS), cancer-specific survival (CSS) and local control (LC) rates were 52.1%, 57.8%, and 68.2%, respectively. Among them, 25 patients had superficial (cT1a-b) esophageal cancers, and the 2-year OS, CSS, and LC rates were 80.0%, 87.3%, and 81.6%, respectively. Multivariate analysis revealed that cT disease (P < 0.001) and tumor location (P = 0.022) were the significant factors for OS. The incidence of grade 3 or higher toxicities were 9.9%, including grade 3 esophagitis (2 patients, 2.8%) and grade 4 or 5 trachea-esophageal fistula (5 patients, 7.1%).High-dose RT alone by moderate hypofractionation had led to reasonable clinical outcomes at acceptable toxicity risk in thoracic esophageal cancer patients who are medically unfit or refuse surgery or chemotherapy, especially for the patients having superficial lesion. PMID:27537591

  6. A novel triple therapy for ITP using high-dose dexamethasone, low-dose rituximab, and cyclosporine (TT4)

    PubMed Central

    Choi, Philip Young-Ill; Roncolato, Fernando; Badoux, Xavier; Ramanathan, Sundra; Ho, Shir-Jing

    2015-01-01

    Promising reports of combination immunosuppression with high-dose dexamethasone and rituximab for the treatment of primary immune thrombocytopenia (ITP) have recently emerged. They suggest a potential to further optimize the efficacy of therapy. We investigate the use of a novel combination of conventional therapies in ITP given over 4 weeks. From 2011 to 2014, 20 patients were prospectively enrolled onto a single-arm phase 2b study to describe the safety, efficacy, and tolerability of oral dexamethasone 40 mg for days 1 to 4, oral cyclosporine 2.5 to 3 mg/kg daily for day 1 to 28, and intravenous low-dose rituximab 100 mg for days 7, 14, 21, and 28. There were no therapy-related serious adverse side effects, 6-month response rate was 60%, and treatment was well tolerated. Responders enjoyed relapse-free survivals of 92% and 76%, respectively, at 12 and 24 months. This study highlights the possibility of achieving an enduring remission from 4 weeks of therapy. This study is registered at www.anzctr.org.au (#ANZCTRN12611000015943). PMID:25972158

  7. Nasal Symptoms After Radioiodine Therapy: A Rarely Described Side Effect with Similar Frequency to Lacrimal Dysfunction

    PubMed Central

    2014-01-01

    Background: Salivary and lacrimal side effects of radioiodine therapy have been carefully described. However, nasal side effects are rarely described. The objective of this study was to document the frequency of nasal side effects in comparison to the already well-documented lacrimal side effects and to determine contributing risk factors. Methods: A retrospective review of the medical records of 807 patients with differentiated thyroid cancer who received care at an academic medical center was conducted. Four hundred eleven patients who received treatment with radioactive iodine (RAI) were identified and included in the analysis. The frequency of both nasal and lacrimal side effects was ascertained. Factors that may have contributed to patients sustaining nasal damage after RAI therapy were also documented. These factors included radioactive iodine dose, method of preparation for receiving RAI therapy, and patient characteristics. Results: The mean dose of RAI administered was 109 mCi. Forty-three patients (10.5%) and 40 patients (9.7%) developed nasal and lacrimal side effects, respectively, following RAI treatment. The mean time of onset of nasal symptoms was 11 days, compared with 10 months for lacrimal symptoms. Radioiodine dose and body mass index were significantly positively and negatively correlated, respectively, with sustaining nasal side effects (p values of 0.04 and 0.01, respectively). Similarly, both RAI dose and body mass index were significantly correlated, positively and negatively, respectively, with sustaining lacrimal side effects (p values of 0.02 and 0.01). Preparation for treatment using a withdrawal protocol was associated with increased risk of both nasal and lacrimal side effects, compared with a recombinant human thyrotropin (rhTSH) protocol (p values of <0.01 and 0.01). The odds ratios (95% confidence interval [CI]) for nasal and lacrimal side effects with recombinant rhTSH preparation were 0.22 [0.11–0.44] and 0.37 [0.18–0

  8. High dose sapropterin dihydrochloride therapy improves monoamine neurotransmitter turnover in murine phenylketonuria (PKU).

    PubMed

    Winn, Shelley R; Scherer, Tanja; Thöny, Beat; Harding, Cary O

    2016-01-01

    Central nervous system (CNS) deficiencies of the monoamine neurotransmitters, dopamine and serotonin, have been implicated in the pathophysiology of neuropsychiatric dysfunction in phenylketonuria (PKU). Increased brain phenylalanine concentration likely competitively inhibits the activities of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), the rate limiting steps in dopamine and serotonin synthesis respectively. Tetrahydrobiopterin (BH4) is a required cofactor for TH and TPH activity. Our hypothesis was that treatment of hyperphenylalaninemic Pah(enu2/enu2) mice, a model of human PKU, with sapropterin dihydrochloride, a synthetic form of BH4, would stimulate TH and TPH activities leading to improved dopamine and serotonin synthesis despite persistently elevated brain phenylalanine. Sapropterin (20, 40, or 100mg/kg body weight in 1% ascorbic acid) was administered daily for 4 days by oral gavage to Pah(enu2/enu2) mice followed by measurement of brain biopterin, phenylalanine, tyrosine, tryptophan and monoamine neurotransmitter content. A significant increase in brain biopterin content was detected only in mice that had received the highest sapropterin dose, 100mg/kg. Blood and brain phenylalanine concentrations were unchanged by sapropterin therapy. Sapropterin therapy also did not alter the absolute amounts of dopamine and serotonin in brain but was associated with increased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), dopamine and serotonin metabolites respectively, in both wild type and Pah(enu2/enu2) mice. Oral sapropterin therapy likely does not directly affect central nervous system monoamine synthesis in either wild type or hyperphenylalaninemic mice but may stimulate synaptic neurotransmitter release and subsequent metabolism. PMID:26653793

  9. [A Case of a Multidisciplinary Team Approach to Serious Hand-Foot Syndrome Induced by High-Dose Cytarabine Therapy].

    PubMed

    Sakurada, Hiroaki; Aoi, Miki; Yuge, Masaaki; Sugimura, Yuriko; Kitamura, Kunio; Yamamura, Masumi; Tachi, Tomoya; Teramachi, Hitomi

    2016-07-01

    A 40's year-old female patient with acute myeloblastic leukemia received high-dose cytarabine(HD-Ara-C)as her third induction therapy. Because the pharmacist in charge noticed on a prior interview that she had experienced a mild skin eruption similar to hand-foot syndrome(HFS)in the previous round oftherapy(idarubicin and cytarabine), heparinoid lotion and hypoallergenic soap were used to prevent HFS. However, HFS occurred on day 3, and further developed on day 6 to grade 3 with painful erythema, swelling, and paresthesia affecting the entire surface of both hands. We cared for her with moisturization, lifestyle guidance, rotation of steroid ointment, and occlusive dressing techniques according to a multidisciplinary team approach composed ofa hematologist, dermatologist, pharmacist, and nurse. Her symptoms resolved on day 40. PMID:27431642

  10. Step-down from high dose fixed combination therapy in asthma patients: a randomized controlled trial

    PubMed Central

    2012-01-01

    Background Asthma guidelines suggest that therapy can be reduced once asthma is controlled. Despite these recommendations, asthmatic patients are seldom stepped down in clinical practice, and questions remain about when and how to reduce asthma therapy. The purpose of the present study was to evaluate lung function and asthma control in patients who were stepped down from the highest recommended dose of inhaled corticosteroid/long acting β2 agonist combination therapy. Methods This was a prospective, randomised, controlled, two-arm parallel group study. Asthmatic patients who were fully controlled with a high daily dose (1000/100 μg) of fluticasone/salmeterol were randomly assigned to 6 months of open-label treatment with either 500/100 μg fluticasone/salmeterol Diskus daily or 400/24 μg extrafine beclomethasone/formoterol pMDI daily. The primary outcome was the change in morning peak expiratory flow (PEF) values between baseline and the end of treatment. The secondary outcomes included asthma control and exacerbation frequency. Results Four hundred twenty-two patients were included in the analysis. The PEF values remained above 95% of the predicted values throughout the study. The end-study morning PEF rates showed equivalence between the groups (difference between means, 2.49 L/min; 95% CI, -13.43 to 18.42). No changes from baseline were detected in PEF and forced expiratory volume in 1 second measured at the clinics, in the symptom scores or in the use of rescue medication. Asthma control was maintained in 95.2% of the patients at 6 months. No significant differences between the groups were detected in any other parameter, including exacerbation frequency and adverse events. Conclusions Stepping down patients whose asthma is controlled with the highest recommended dose of fluticasone/salmeterol to either 500/100 μg fluticasone/salmeterol daily or 400/24 μg extra-fine beclomethasone/formoterol daily provides comparable maintenance of lung

  11. Adjuvant Therapy with High-Dose Medroxyprogesterone Acetate for Operable Breast Cancer.

    PubMed

    Koyama

    1999-04-25

    BACKGROUND: Medroxyprogesterone acetate (MPA) produces a comparable or higherresponse rate in metastatic breast cancer compared with tamoxifen which is alsocommonly used for adjuvant endocrine therapy. Several studies in the West have indicated the efficacy of MPA when used as an adjuvant to surgery in certain subsets of patients. The present study was undertaken as a multicenter open study in Japan to investigate the safety and efficacy of MPA in adjuvant endocrine therapy. Method and Patients: A combination of 800 mg/day MPA and a fluorouracil compound for 6 months was given postoperatively to 119 patients with stage II or IIIabreast cancer in 32 participating hospitals between June 1987 and June 1989. RESULTS: Among the 119 patients, 59 patients (49.6%) experienced some kind ofadverse reaction. The major adverse reaction was abnormal menstruation, seen in 13 (25.0%) of the 52 premenopausal patients. Vaginal bleeding was a major adverse reaction in the 67 postmenopausal patients (8/67 or 11.9%). An increase in body weight and moon face were observed in 23 (19.3%) and 9 (7.6%) of the 119 patients, respectively. Administration of drugs was discontinued because of adversereaction in 17 patients (14.3%), and dose reduction or temporary suspension wasnecessary in 7 patients (5.9%). Increase in body weight was the main reason fordiscontinuation of the treatment. No severe adverse reactions were observed. After a median follow-up of 74.5 months (range, 2.2-90.0 months), 84 of the 119 patients are alive with no evidence of disease. The 3-year and 5-year disease-freesurvival rates were 88.2% and 82.6% in stage II patients, and 64.7% and 52.9% in stage IIIa patients, respectively. The 3-year and 5-year disease-free survivalrates according to age were 87.8% and 79.3% in patients aged 50 years or more, and 78.6% and 71.4% in patients aged under 50 years. CONCLUSION: These results show that 800 mg/day MPA plus a fluorouracil compound can be administered with acceptable

  12. Efficient multicistronic co-expression of hNIS and hTPO in prostate cancer cells for nonthyroidal tumor radioiodine therapy.

    PubMed

    Li, Guoquan; Xiang, Lei; Yang, Weidong; Wang, Zhe; Wang, Jing; Chen, Kai

    2012-01-01

    Radioiodine therapy has proven to be a safe and effective approach in the treatment of differentiated thyroid cancer. Similar treatment strategies have been exploited in nonthyroidal malignancies by transfecting hNIS gene into tumor cells or xenografts. However, rapid radioiodine efflux is often observed after radioiodine uptake, limiting the overall antitumor effects. In this study, we aimed at constructing multicistronic co-expression of hNIS and hTPO genes in tumor cells to enhance the radioiodine uptake and prolong the radioiodine retention. Driven by the cytomegalovirus promoter, hNIS and hTPO were simultaneously inserted into the expression cassette of adenoviral vector. An Ad5 viral vector (Ad-CMV-hTPO-T2A-hNIS) was assembled as a gene therapy vehicle by Gateway technology and 2A method. The co-expression of hNIS and hTPO genes was confirmed by a double-label immunofluorescence assay. The radioiodine ((125)I) uptake and efflux effects induced by co-expression of hNIS and hTPO genes were determined in transfected and non-transfected PC-3 cells. Significantly higher uptake (6.58 ± 0.56 fold, at 1 h post-incubation) and prolonged retention (5.47 ± 0.36 fold, at 1 h of cell efflux) of radioiodine ((125)I) were observed in hNIS and hTPO co-expressed PC-3 cells as compared to non-transfected PC-3 cells. We concluded that the new virus vector displayed favorable radioiodine uptake and retention properties in hNIS-hTPO transfected PC-3 cells. Our study will provide valuable information on improving the efficacy of hNIS-hTPO co-mediated radioiodine gene therapy. PMID:23145364

  13. Does Radioiodine Therapy in Patients with Differentiated Thyroid Cancer Increase the Frequency of Another Malignant Neoplasm?

    PubMed Central

    Hirosawa, Renata Midori; Marivo, Monica; Luengo, Juliana de Moura Leite; Tagliarini, Jose Vicente; Castilho, Emanuel Cellice; Marques, Mariangela de Alencar; Kiy, Yoshio; Marone, Marilia Martins Silveira; Silveira, Liciana Vaz de Arruda; Mazeto, Glaucia Maria Ferreira da Silva

    2011-01-01

    Objectives. To compare the frequency of another primary malignancy in patients with differentiated thyroid carcinoma (DTC) who received radioiodine therapy or not (131I). Material and Methods. 168 cases of DTC patients were retrospectively evaluated as to the frequency of another neoplasia by comparing patients with and without it, taking into account clinical, laboratory, and therapeutic parameters. Results. Another primary malignancy occurred in 8.9% of patients. Of these, 53.3% showed the malignancy before 131I and 46.7% after it. By comparing both groups, the age at the moment of diagnosis of another neoplasia was 46.1 ± 20.2 years for the group before 131I therapy and of 69.4 ± 11.4 years for the group after it (P = 0.02). Of the 148 patients treated with 131I, 4.7% developed another malignancy. The latter were older (61 ± 17 years) than those who did not show another cancer type (44.1 ± 14.2 years) (P < 0.05). Conclusion. The frequency of another neoplasia found after 131I was similar to that found before 131I. PMID:22084737

  14. High-Dose Vitamin D and Calcium Attenuates Bone Loss with Antiretroviral Therapy Initiation

    PubMed Central

    Overton, Edgar Turner; Chan, Ellen S.; Brown, Todd T.; Tebas, Pablo; McComsey, Grace A.; Melbourne, Kathleen M.; Napoli, Andrew; Hardin, William Royce; Ribaudo, Heather J.; Yin, Michael T.

    2015-01-01

    Background Antiretroviral therapy (ART) initiation for HIV-1 infection is associated with 2-6% loss in bone mineral density (BMD). Objective To evaluate vitamin D3 (4000 IU daily) plus calcium (1000 mg calcium carbonate daily) supplementation on bone loss associated with ART initiation. Design 48-week prospective, randomized, double-blind, placebo-controlled study. Setting Thirty nine AIDS Clinical Trials Network research units. Participants ART-naïve HIV-infected adults. Measurements BMD by dual-energy X-ray absorptiometry (DXA); 25-hydroxy vitamin D (25(OH)D) levels, parathyroid hormone (PTH), phosphate metabolism, markers of bone turnover and systemic inflammation. Results 165 eligible subjects were randomized (79 Vitamin D/calcium (VitD/Cal); 86 placebo); 142 subjects with evaluable DXA data were included in the primary analysis. The study arms were well-balanced at baseline: median age 33 years; 90% male; 33% non-Hispanic black; median CD4 count 341 cells/mm3; and median 25(OH)D 23 ng/mL (57 nmol/L). At 48 weeks, subjects receiving placebo had greater decline in total hip BMD than VitD/Cal: −3.19% median change (1st-3rd quartile (Q1, Q3) −5.12%, −1.02%) vs. (−1.46% −3.16%,−0.40%). respectively (p=0.001). Lumbar spine BMD loss for the two groups was similar: −2.91% (−4.84%, −1.06%) vs. −1.41% (−3.78%, 0.00%), (p=0.085). At week 48, 90% of participants achieved HIV-1 RNA <50 copies/mL. Levels of 25(OH)D3 increased in the VitD/Cal but not the placebo group: median change of 24.5 (14.6, 37.8) vs. 0.7 (−5.3, 4.3) ng/mL, respectively (p<0.001). Additionally, increases in markers of bone turnover were blunted in the VitD/Cal group. Limitations No international sites were included; only 48 weeks of follow up Conclusion Vitamin D/calcium supplementation mitigates the loss of BMD seen with initiation of efavirenz/emtricitabine/tenofovir, particularly at the total hip, which is the site of greatest concern for fragility fracture. Primary Funding

  15. The effect of high dose atorvastatin therapy on lipids and lipoprotein subfractions in overweight patients with type 2 diabetes.

    PubMed

    Lawrence, J M; Reid, J; Taylor, G J; Stirling, C; Reckless, J P D

    2004-05-01

    Few data are available on the effects of high dose statin therapy on lipoprotein subfractions in type 2 diabetes. In a double blind randomised placebo-controlled trial we have studied the effects of 80 mg atorvastatin over 8 weeks on LDL, VLDL and HDL subfractions in 40 overweight type 2 diabetes patients. VLDL and LDL subfractions were prepared by density gradient ultracentrifugation. Triglycerides, cholesterol, total protein and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. Atorvastatin 80 mg produced significant falls in LDL subfractions (LDL(1) 66.2 mg/dl:36.6 mg/dl, LDL(2) 118:56.6 mg/dl, LDL(3) 36.9:19.9 mg/dl all P < 0.01 relative to placebo) and VLDL subfractions (VLDL(1) 55:22.1 mg/dl, VLDL(2) 40.1:19.1 mg/dl, VLDL(3) 52.6:30 mg/dl all P < 0.01 relative to placebo). There was no change in the proportion of LDL present as LDL(3). There was a reduction in the proportion of VLDL as VLDL(1) and a reciprocal increase in the proportion as VLDL(3). Changes in VLDL subfractions were associated with changes in lipid composition, particularly a reduction in cholesterol ester and a reduction in the cholesterol ester/triglyceride ratio. Effects on HDL subfractions were largely neutral. High dose atorvastatin produces favourable effects on lipoprotein subfractions in type 2 diabetes which may enhance antiatherogenic potential. PMID:15135263

  16. Role of Maintenance Therapy after High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation in Aggressive Lymphomas: A Systematic Review.

    PubMed

    Taverna, Josephine A; Yun, Seongseok; Jonnadula, Jayasree; Saleh, Ahlam; Riaz, Irbaz Bin; Abraham, Ivo; Yeager, Andrew M; Persky, Daniel O; McBride, Ali; Haldar, Subrata; Anwer, Faiz

    2016-07-01

    Significant uncertainty exists in regard to the efficacy of maintenance therapy after high-dose chemotherapy (HDC) as well as autologous stem cell transplantation (ASCT) for the treatment of patients with aggressive lymphoma. A systematic review was performed to evaluate the effectiveness of post-ASCT maintenance therapy in patients with relapsed/refractory lymphoma. A comprehensive literature search yielded 4476 studies and a total of 42 studies (11 randomized controlled trials [RCT], 9 retrospective comparative studies, and 22 single-arm studies) were included in the systematic review. There was significant heterogeneity in study design, chemotherapeutic regimens, post-ASCT maintenance strategies, patient enrollment criteria, and study endpoints. Our findings suggest that post-ASCT maintenance immune-targeting strategies, including PD-1/PD-L1 blocking antibodies, rituximab, and brentuximab, may improve progression-free survival but not overall survival. Collectively, the results indicate a need for testing new strategies with well-designed and adequately powered RCTs to better address the role of post-ASCT maintenance in relapsed/refractory lymphomas. PMID:26899562

  17. Estimation of patient attenuation factor for iodine-131 based on direct dose rate measurements from radioiodine therapy patients.

    PubMed

    Soliman, Khaled; Alenezi, Ahmed

    2015-02-01

    The aim of the study was to measure the actual dose at 1 m from the patients per unit activity with the aim of providing a more accurate prediction of the dose levels around radioiodine patients in the hospital, as well as to compare our results with the literature. In this work the demonstration of a patient body tissue attenuation factor is verified by comparing the dose rates measured from the patients with those measured from the unshielded radioiodine capsules immediately after administration of the radioactivity. The normalized dose rate per unit activity is therefore proposed as an operational quantity that can be used to predict exposure rates to staff and patients' relatives. The average dose rate measured from our patient per unit activity was 38.4±11.8 μSv/h/GBq. The calculated attenuation correction factor based on our measurements was 0.55±0.17. The calculated dose rate from a radioiodine therapy patient should normally include a factor accounting for patient body tissue attenuation and scatter. The attenuation factor is currently neglected and not applied in operational radiation protection. Realistic estimation of radiation dose levels from radioiodine therapy patients when properly performed will reduce the operational cost and optimize institutional radiation protection practice. It is recommended to include patient attenuation factors in risk assessment exercises - in particular, when accurate estimates of total effective doses to exposed individuals are required when direct measurements are not possible. The information provided about patient attenuation might benefit radiation protection specialists and regulators. PMID:25279710

  18. Assessment of radioiodine therapy efficacy for treatment of differentiated thyroid cancer patients with pulmonary metastasis undetected by chest computed tomography

    PubMed Central

    LONG, BIN; YANG, MENGDI; YANG, ZHIWEN; YI, HEQING; LI, LINFA

    2016-01-01

    Radioiodine therapy (RAI) has proven effective for the treatment of patients exhibiting differentiated thyroid cancer (DTC) with pulmonary metastases. However, the early detection of metastasis remains challenging, and various studies have reported variations in radioiodine treatment efficacy. The present study investigated whether RAI is an effective method for the treatment of DTC with pulmonary metastases undetected by computed tomography (CT). A retrospective study was performed, analyzing iodine-131 (131I) therapy in 21 DTC patients with lung metastases that were undetected by CT. All 21 patients were initially treated with radioiodine ablation of thyroid remnants. Routine chest CT was performed prior to 131I treatment without diagnostic radioiodine whole-body scanning (DxWBS), and post-therapeutic WBS was performed 3–5 days subsequent to oral administration of 131I. The overall effectiveness rate was 95.2% (20/21). The rates for complete response (CR), partial response and no response were 23.8 (5/21), 71.4 (15/21) and 4.8% (1/21), respectively. There were 12 patients with diffuse uptake, and the remaining 9 patients demonstrated focused and low uptake. The difference in CR rate between diffuse uptake and focused uptake patients was not statistically significant (P=0.123). A correlation was observed between thyroglobulin (Tg) levels and extrapulmonary metastases. All patients exhibited extrapulmonary metastases when Tg levels were >87.5 ng/ml (area under receiver operating characteristic curve, 1.0; P<0.001). Overall, DTC patients with lung metastases undetected by CT imaging responded well to 131I radiotherapy and demonstrated a positive prognosis. Serum Tg levels prior to 131I treatment may correlate with metastasis, and this may suggest a requirement for the performance of DxWBS prior to radiotherapy. PMID:26893676

  19. A randomized trial of high-dose ciprofloxacin versus azlocillin and netilmicin in the empirical therapy of febrile neutropenic patients.

    PubMed

    Johnson, P R; Liu Yin, J A; Tooth, J A

    1992-08-01

    A prospective, randomized trial comparing monotherapy with high-dose ciprofloxacin versus a standard combination regimen of azlocillin and netilmicin in the empirical treatment of febrile episodes in neutropenic patients was performed. One hundred and forty-six patient episodes were randomized, but ten (seven ciprofloxacin and three azlocillin/netilmicin) were considered unevaluable for efficacy, and three episodes were withdrawn due to incorrect randomization or non-neutropenia. Of the remaining 133 episodes, infections resolved without modification of therapy in 25/66 (38%) versus 28/67 (42%) of ciprofloxacin and azlocillin/netilmicin treated groups respectively (P = 0.72). Considering all randomized episodes, therapy was modified in 46/73 (63%) episodes with ciprofloxacin and 39/70 (56%) with azlocillin/netilmicin (P = 0.40). Of 73 patient episodes randomized to ciprofloxacin, 25 (34%) received oral follow-on therapy after a median of three days of intravenous therapy. Infections were microbiologically documented in 31/73 (42%) ciprofloxacin and 32/70 (46%) azlocillin/netilmicin, of which 8/27 (30%) and 14/31 (45%) of evaluable episodes resolved without modification of therapy respectively (P = 0.28). Gram-positive organisms accounted for 78% of all organisms cultured with 36% coagulase-negative staphylococci. Bacteriological eradication was recorded in 18/24 (75%) and 26/29 (90%) evaluable patient episodes treated with ciprofloxacin and azlocillin/netilmicin respectively (P = 0.27). Superinfections were seen in 14% of episodes in both groups, and subsequent infections in 12% ciprofloxacin and 14% azlocillin/netilmicin treated patients. Two patients (one ciprofloxacin and one azlocillin/netilmicin) died within 48 h of randomization, and a further 13 patients (four ciprofloxacin and nine azlocillin/netilmicin) died before resolution of neutropenia. Adverse events were recorded in 9% and 15% of ciprofloxacin and azlocillin/netilmicin treated patients respectively

  20. Thiotepa-based high-dose therapy for autologous stem cell transplantation in lymphoma: a retrospective study from the EBMT.

    PubMed

    Sellner, L; Boumendil, A; Finel, H; Choquet, S; de Rosa, G; Falzetti, F; Scime, R; Kobbe, G; Ferrara, F; Delmer, A; Sayer, H; Amorim, S; Bouabdallah, R; Finke, J; Salles, G; Yakoub-Agha, I; Faber, E; Nicolas-Virelizier, E; Facchini, L; Vallisa, D; Zuffa, E; Sureda, A; Dreger, P

    2016-02-01

    Clinical information about thiotepa-based autologous stem cell transplantation (auto-SCT) outside the primary central nervous system lymphoma (PCNSL) field is sparse. In this registry-based retrospective study, we evaluated potential risks and benefits of thiotepa-based preparative regimens compared with BEAM (carmustine, etoposide, cytarabine, melphalan) in auto-SCT for diffuse large B-cell lymphoma (DLBCL, excluding PCNSL), follicular lymphoma (FL) or Hodgkin lymphoma (HL). A total of 14 544 patients (589 thiotepa and 13 955 BEAM) met the eligibility criteria, and 535 thiotepa- and 1031 BEAM-treated patients were matched in a 1:2 ratio for final comparison. No significant differences between thiotepa and BEAM groups for any survival end point were identified in the whole sample or disease entity subsets. For a more detailed analysis, 47 TEAM (thiotepa, etoposide, cytarabine, melphalan)-treated patients were compared with 75 matched BEAM patients with additional collection of toxicity data. Again, there were no significant differences between the two groups for any survival end point. In addition, the frequency of common infectious and non-infectious complications including secondary malignancies was comparable between TEAM and BEAM. These results indicate that thiotepa-based high-dose therapy might be a valuable alternative to BEAM in DLBCL, HL and FL. Further evaluation by prospective clinical trials is warranted. PMID:26569093

  1. Clinical Studies of Nonpharmacological Methods to Minimize Salivary Gland Damage after Radioiodine Therapy of Differentiated Thyroid Carcinoma: Systematic Review.

    PubMed

    Christou, Andri; Papastavrou, Evridiki; Merkouris, Anastasios; Frangos, Savvas; Tamana, Panayiota; Charalambous, Andreas

    2016-01-01

    Purpose. To systematically review clinical studies examining the effectiveness of nonpharmacological methods to prevent/minimize salivary gland damage due to radioiodine treatment of differentiated thyroid carcinoma (DTC). Methods. Reports on relevant trials were identified by searching the PubMed, CINHAL, Cochrane, and Scopus electronic databases covering the period 01/2000-10/2015. Inclusion/exclusion criteria were prespecified. Search yielded eight studies that were reviewed by four of the present authors. Results. Nonpharmacological methods used in trials may reduce salivary gland damage induced by radioiodine. Sialogogues such as lemon candy, vitamin E, lemon juice, and lemon slice reduced such damage significantly (p < 0.0001, p < 0.05, p < 0.10, and p < 0.05, resp.). Parotid gland massage also reduced the salivary damage significantly (p < 0.001). Additionally, vitamin C had some limited effect (p = 0.37), whereas no effect was present in the case of chewing gum (p = 0.99). Conclusion. The review showed that, among nonpharmacological interventions, sialogogues and parotid gland massage had the greatest impact on reducing salivary damage induced by radioiodine therapy of DTC. However, the studies retrieved were limited in number, sample size, strength of evidence, and generalizability. More randomized controlled trials of these methods with multicenter scope and larger sample sizes will provide more systematic and reliable results allowing more definitive conclusions. PMID:27446226

  2. Clinical Studies of Nonpharmacological Methods to Minimize Salivary Gland Damage after Radioiodine Therapy of Differentiated Thyroid Carcinoma: Systematic Review

    PubMed Central

    Papastavrou, Evridiki; Frangos, Savvas; Tamana, Panayiota

    2016-01-01

    Purpose. To systematically review clinical studies examining the effectiveness of nonpharmacological methods to prevent/minimize salivary gland damage due to radioiodine treatment of differentiated thyroid carcinoma (DTC). Methods. Reports on relevant trials were identified by searching the PubMed, CINHAL, Cochrane, and Scopus electronic databases covering the period 01/2000–10/2015. Inclusion/exclusion criteria were prespecified. Search yielded eight studies that were reviewed by four of the present authors. Results. Nonpharmacological methods used in trials may reduce salivary gland damage induced by radioiodine. Sialogogues such as lemon candy, vitamin E, lemon juice, and lemon slice reduced such damage significantly (p < 0.0001, p < 0.05, p < 0.10, and p < 0.05, resp.). Parotid gland massage also reduced the salivary damage significantly (p < 0.001). Additionally, vitamin C had some limited effect (p = 0.37), whereas no effect was present in the case of chewing gum (p = 0.99). Conclusion. The review showed that, among nonpharmacological interventions, sialogogues and parotid gland massage had the greatest impact on reducing salivary damage induced by radioiodine therapy of DTC. However, the studies retrieved were limited in number, sample size, strength of evidence, and generalizability. More randomized controlled trials of these methods with multicenter scope and larger sample sizes will provide more systematic and reliable results allowing more definitive conclusions. PMID:27446226

  3. Verification of the agreement of two dosimetric methods with radioiodine therapy in hyperthyroid patients

    SciTech Connect

    Canzi, Cristina; Zito, Felicia; Voltini, Franco; Reschini, Eugenio; Gerundini, Paolo

    2006-08-15

    The aim of this study was to verify the capability of an MIRD formula-based dosimetric method to predict radioiodine kinetics (fraction of administered iodine transferred to the thyroid, U{sub 0}, and effective clearance rate, {lambda}{sub eff}) and absorbed dose after oral therapeutic {sup 131}I administration. The method is based on {sup 123}I intravenous administration and five subsequent gamma camera measured uptake values determined separately on different structures within the thyroid. Another dosimetric method based on only the {sup 123}I 24-h uptake and a fixed {lambda}{sub eff} value was also considered. Eighty-nine hyperthyroid patients (10 with Graves' disease and 79 with autonomously functioning nodules) were studied and 132 thyroidal structures were evaluated. The mean time interval between dosimetry and therapy was 20{+-}10d. Uptake values were measured at 2, 4, 24, 48, and 120 h during dosimetry and at 2, 4, 24, 48, 96, and 168 h during therapy. The value 0.125d{sup -1} was chosen in the fixed-{lambda}{sub eff} method. The planned doses to the target ranged from 120 to 250 Gy depending on the type and severity of hyperthyroidism. The following significant correlations between therapeutic and dosimetric parameters were found: U{sub 0}ther=0.88U{sub 0}dos (r=0.97,p<0.01), {lambda}{sub eff}ther=1.01{lambda}{sub eff}dos (r=0.85,p<0.01), and D{sub estimated}=0.85D{sub planned} (r=0.88,p<0.01). The percent difference between U{sub 0}ther and U{sub 0}dos ranged from -44 to 32% and between {lambda}{sub eff}ther and {lambda}{sub eff}dos from -32 to 48%. U{sub 0}ther was lower than U{sub 0}dos in 74% of cases: this can be explained by the self-stunning effect of {sup 131}I therapeutic activity that produced a dose of about 20 Gy with a maximum dose rate of 0.6 Gy/h over the initial 24-48 h. The differences, {delta}D, between the estimated and the planned doses ranged from -42% (-87 Gy) to 32% (59 Gy); in 73% of cases the difference was within {+-}35 Gy

  4. Determination of Organ Doses in Radioiodine Therapy using Monte Carlo Simulation

    PubMed Central

    Shahbazi-Gahrouei, Daryoush; Ayat, Saba

    2015-01-01

    Radioactive iodine treatment is a type of internal radiotherapy that has been used effectively for the treatment of differentiated thyroid cancer after thyroidectomy. The limit of this method is its affects on critical organs, and hence dosimetry is necessary to consider the risk of this treatment. Scope of this work is the measurement of absorbed doses of critical organs by Monte Carlo simulation and comparing the results with other methods of dosimetry such as direct dosimetry and Medical Internal Radiation Dose (MIRD) method. To calculate absorbed doses of vital organs (thyroid, sternum and cervical vertebrae) via Monte Carlo, a mathematical phantom was used. Since iodine 131 (131I) emmits photon and beta particle, *F8 tallies, which give results in MeV were applied and the results were later converted to cGy by dividing by the mass within the cell and multiplying by 1.6E-8. The absorbed dose obtained by Monte Carlo simulations for 100, 150 and 175 mCi administered 131I was found to be 388.0, 427.9 and 444.8 cGy for thyroid, 208.7, 230.1 and 239.3 cGy for sternum and 272.1, 299.9 and 312.1 cGy for cervical vertebrae. The results of Monte Carlo simulation method had no significant difference with the results obtained via direct dosimetry using thermoluminescent dosimeter-100 and MIRD method. Hence, Monte Carlo is a suitable method for dosimetry in radioiodine therapy. PMID:25709539

  5. Favorable outcomes in elderly patients undergoing high-dose therapy and autologous stem cell transplantation for non-Hodgkin lymphoma.

    PubMed

    Dahi, Parastoo B; Tamari, Roni; Devlin, Sean M; Maloy, Molly; Bhatt, Valkal; Scordo, Michael; Goldberg, Jenna; Zelenetz, Andrew D; Hamlin, Paul A; Matasar, Matthew J; Maragulia, Jocelyn; Giralt, Sergio A; Perales, Miguel-Angel; Moskowitz, Craig H; Sauter, Craig S

    2014-12-01

    High-dose therapy and autologous stem cell transplantation (HDT-ASCT) can offer potential long-term remission or cure in patients with non-Hodgkin lymphoma (NHL). Limited experience is available on the safety and efficacy of HDT-ASCT in elderly patients. This is a single-center, retrospective study examining outcomes of HDT-ASCT for 202 NHL patients, ages 60 years and older, between January 2001 and December 2012. Overall survival (OS) and progression-free survival (PFS) were analyzed according to age at HDT-ASCT, hematopoietic cell transplantation comorbidity index (HCT-CI), NHL histology, and remission status at the time of HDT-ASCT. The median age was 65 years (range, 60 to 74) and the majority had either diffuse large B cell lymphoma (n = 73, 37%) or mantle cell lymphoma (n = 69, 34%). One hundred and fifteen patients (57%) had high HCT-CI scores at the time of HDT-ASCT. With a median follow-up of 3.6 years (range, 4 to 11.9 years) for survivors, PFS and OS at 3 years were 60% (95% confidence interval [CI], 53% to 68%) and 73% (95% CI, 67% to 80%), respectively. Transplantation-related mortality (TRM) was 4% both at 100 days and at 1 year after HDT-ASCT. Age and HCT-CI score were not associated with OS or PFS, and high HCT-CI did not correlate with TRM. Seven patients (4%) developed secondary myelodysplastic syndrome or acute myeloid leukemia at a median of 35 months (range, 6 to 48) after HDT-ASCT. In this single-center cohort of elderly patients with NHL undergoing HDT-ASCT, this intervention was proven tolerable and effective, with results similar to those of historic controls in younger patients. Our data suggest that age alone should not preclude HDT-ASCT in elderly patients. PMID:25175794

  6. Impact of Conditioning Regimen on Outcomes for Patients with Lymphoma Undergoing High-Dose Therapy with Autologous Hematopoietic Cell Transplantation

    PubMed Central

    Logan, Brent; Zhu, Xiaochun; Akpek, Görgün; Aljurf, Mahmoud; Artz, Andrew; Bredeson, Christopher N.; Cooke, Kenneth R.; Ho, Vincent T.; Lazarus, Hillard M.; Olsson, Richard; Saber, Wael; McCarthy, Philip; Pasquini, Marcelo C.

    2015-01-01

    There are limited data to guide the choice of high-dose therapy (HDT) regimen prior to autologous hematopoietic cell transplantation (AHCT) for patients with Hodgkin (HL) and non-Hodgkin lymphoma (NHL). We studied 4,917 patients (NHL n=3,905; HL n=1,012) who underwent AHCT from 1995-2008 using the most common HDT platforms: BEAM (n=1730), CBV (n=1853), BuCy (n=789), and TBI-containing (n=545). CBV was divided into CBVhigh and CBVlow based on BCNU dose. We analyzed the impact of regimen on development of idiopathic pulmonary syndrome (IPS), transplant-related mortality (TRM), progression free and overall survival (PFS and OS). The 1-year incidence of IPS was 3-6% and was highest in recipients of CBVhigh (HR 1.9) and TBI (HR 2.0) compared to BEAM. 1-year TRM was 4-8% and was similar between regimens. Among patients with NHL, there was a significant interaction between histology, HDT regimen, and outcome. Compared to BEAM, CBVlow (HR 0.63) was associated with lower mortality in follicular lymphoma (p<0.001), and CBVhigh (HR1.44) with higher mortality in diffuse large B-cell lymphoma (p=0.001). For patients with HL, CBVhigh (HR1.54), CBVlow (HR1.53), BuCy (HR1.77) and TBI (HR 3.39) were associated with higher mortality compared to BEAM (p<0.001). The impact of specific AHCT regimen on post transplant survival is different depending on histology; therefore, further studies are required to define the best regimen for specific diseases. PMID:25687795

  7. Differential cytotoxic responses to low- and high-dose photodynamic therapy in human gastric and bladder cancer cells.

    PubMed

    Yoo, Je-Ok; Lim, Young-Cheol; Kim, Young-Myeong; Ha, Kwon-Soo

    2011-10-01

    Here, we present differential cytotoxic responses to two different doses of photodynamic therapies (PDTs; low-dose PDT [LDP] and high-dose PDT [HDP]) using a chlorin-based photosensitizer, DH-II-24, in human gastric and bladder cancer cells. Fluorescence-activated cell sorting analysis using Annexin V and propidium iodide (PI) showed that LDP induced apoptotic cell death, whereas HDP predominantly caused necrotic cell death. The differential cytotoxic responses to the two PDTs were further confirmed by a DiOC(6) and PI double-staining assay via confocal microscopy. LDP, but not HDP, activated caspase-3, which was inhibited by Z-VAD, Trolox, and BAPTA-AM. LDP and HDP demonstrated opposite effects on intracellular reactive oxygen species (ROS)/Ca(2+) signals; LDP stimulated intracellular ROS production, contributing to a transient increase of intracellular Ca(2+) , whereas HDP induced a massive and prolonged elevation of intracellular Ca(2+) responsible for the transient production of intracellular ROS. In addition, the two PDTs also increased in situ transglutaminase 2 (TG2) activity, with a higher stimulation by HDP, and this increase in activity was prevented by Trolox, BAPTA-AM, and TG2-siRNA. LDP-induced apoptotic cell death was strongly inhibited by Trolox and TG2-siRNA and moderately suppressed by BAPTA-AM. However, HDP-mediated necrotic cell death was partially inhibited by BAPTA-AM but not by TG2-siRNA. Thus, these results demonstrate that LDP and HDP induced apoptotic and necrotic cell death by differential signaling mechanisms involving intracellular Ca(2+) , ROS, and TG2. PMID:21678478

  8. Effect of a Low Iodine Diet vs. Restricted Iodine Diet on Postsurgical Preparation for Radioiodine Ablation Therapy in Thyroid Carcinoma Patients

    PubMed Central

    Lim, Chi Young; Kim, Jung-Yeon; Yoon, Mi-Jin; Chang, Hang Seok; Park, Cheong Soo

    2015-01-01

    Purpose The radioiodine ablation therapy is required for patients who underwent a total thyroidectomy. Through a comparative review of a low iodine diet (LID) and a restricted iodine diet (RID), the study aims to suggest guidelines that are suitable for the conditions of Korea. Materials and Methods The study was conducted with 101 patients. With 24-hour urine samples from the patients after a 2-week restricted diet and after a 4-week restricted diet, the amount of iodine in the urine was estimated. The consumed radioiodine amounts for 2 hours and 24 hours were calculated. Results This study was conducted with 47 LID patients and 54 RID patients. The amounts of iodine in urine, the 2-week case and 4-week case for each group showed no significant differences. The amounts of iodine in urine between the two groups were both included in the range of the criteria for radioiodine ablation therapy. Also, 2 hours and 24 hours radioiodine consumption measured after 4-week restrictive diet did not show statistical differences between two groups. Conclusion A 2-week RID can be considered as a type of radioiodine ablation therapy after patients undergo a total thyroidectomy. PMID:26069126

  9. Image guided radiation therapy boost in combination with high-dose-rate intracavitary brachytherapy for the treatment of cervical cancer

    PubMed Central

    Wang, Xianliang; Li, Jie; Yuan, Ke; Yin, Gang; Wan, Bin

    2016-01-01

    Purpose The purpose of this study was to demonstrate the dosimetric and clinical feasibility of image guided radiation therapy (IGRT) combined with high-dose-rate (HDR) intracavitary brachytherapy (ICBT) to improve dose distribution in cervical cancer treatment. Material and methods For 42 cervical cancer patients, magnetic resonance imaging (MRI) scans were acquired after completion of whole pelvic irradiation 45-46 Gy and 5 fractions of B + I (ICBT + IGRT) treatment were subsequently received. The high risk clinical target volume (HRCTV), intermediate risk clinical target volume (IRCTV), bladder, rectum, and sigmoid were contoured on the computed tomography (CT) scans. The total planning aim doses for HRCTV was D90% > 85 Gy, whilst constraints for rectum and sigmoid were D2cc < 75 Gy and D2cc < 90 Gy for bladder in terms of an equivalent dose in 2 Gy (EQD2) for external beam radiotherapy (EBRT) and brachytherapy boost. The IGRT plan was optimized on top of the ICBT dose distribution. A dosimetric comparison was made between B + I and optimized ICBT (O-ICBT) only. Results The mean D90% of HRCTV was comparable for B + I and O-ICBT (p = 0.82). For B + I plan, HRCTV D100%, IRCTV D100%, and IRCTV D90% were significantly increased by a mean of 10.52 Gy, 5.61 Gy, and 2.70 Gy, respectively (p < 0.01). The D2cc for bladder, rectum, and sigmoid were lower by a mean of 21.36, 6.78, and 10.65 Gy, respectively (p < 0.01). The mean rectum V60 Gy value over 42 patients was almost the same for both techniques but for bladder and sigmoid B + I had higher V60 Gy mean values as compared with the O-ICBT. Conclusions B + I can improve dose distribution in cervical cancer treatment; it could be useful for tumors extended beyond the reach of intracavitary/interstitial brachytherapy (IC/ISBT) or for centers that are inexperienced or ill-equipped with IC/ISBT techniques. Additional confirmatory prospective studies with larger numbers of patients and longer follow-up are required to

  10. Losartan/hydrochlorothiazide combination therapy surpasses high-dose angiotensin receptor blocker in the reduction of morning home blood pressure in patients with morning hypertension.

    PubMed

    Hanayama, Yoshihisa; Uchida, Haruhito Adam; Nakamura, Yoshio; Makino, Hirofumi

    2012-01-01

    Angiotensin receptor blockers (ARBs) are the first-line antihypertensive agents. In clinical practice, it is often difficult to achieve the recommended blood pressure level by ARBs in their ordinal dosages alone. This study examined the practical efficacy of a combination therapy of ARB with thiazide diuretics for lowering morning home blood pressure (MHBP) in comparison to high-dose ARB therapy in patients with morning hypertension administered an ordinal dosage of ARB. This study was performed in a prospective, randomized, open-labeled and blind-endpoint fashion. Patients were considered to have morning hypertension when their self-measured systolic MHBPs were 135mmHg or higher, irrespective of their diastolic MHBP and office blood pressures (OBPs). Forty-eight outpatients with morning hypertension receiving the ordinal dosage of ARB were given either losartan/hydrochlorothiazide (n = 26) or high-dose ARB (n = 22) in place of their previously prescribed ARB. No change in any medication was permitted during this period. Decreases of both systolic and diastolic MHBP after 3 months of treatment were significantly greater in the losartan/hydrochlorothiazide group than in the high-dose ARB group (p < 0.05, respectively). The ratio of adverse events was somewhat high (23.1% in the losartan/hydrochlorothiazide group, 9.1% in the high-dose ARB group, respectively). However, there were no significant differences in any particular adverse event between groups. This study suggested losartan/hydrochlorothiazide might be superior to high-dose ARB for reducing morning home blood pressure. PMID:23254579

  11. Survival outcome of radioiodine therapy in post thyroidectomy thyroid carcinoma patients: Outcome of long term follow up

    NASA Astrophysics Data System (ADS)

    Haque, F.; Nahar, N.; Sultana, S.; Nasreen, F.; Jabin, Z.; Alam, A. S. M. M.

    2016-03-01

    The overall prognosis of patients with thyroid carcinoma is excellent whenever managed following best practice guidelines. Objective: To calculate sex and age group affected by thyroid cancer; to compare between single or multiple dose of radio ablation needed after thyroidectomy and to determine the percentage of patients become disease free during their follow up. Methods: This was a retrospective study done in NINMAS, Bangladesh on 687 patients from 1984 to 2004. In all cases total or near total thyroidectomy was done before commencing radioiodine therapy. Patients TG level, neck ultrasonography, thyroid scan, whole body I131 scans, neck examination were done every six monthly/yearly. Results: Among 687 patients, female were more sufferers (68.1%) and female to male ratio was 2:1. Age group 19-40 years was mostly affected (57.8%). Most common type seen was papillary carcinoma (81.8%). After ablation 100 patients did not follow-up. Total 237 patients discontinued within 4 years. Remaining 450 patients undergone regular follow-up for 5 years and more, 394 were disease free (87.6%). Total recurrence of metastasis was 23 and 12 patients expired at different times. Conclusions: Long-term regular follow-up is necessary after radioiodine ablation to become free of disease.

  12. Ion recombination correction factors (P(ion)) for Varian TrueBeam high-dose-rate therapy beams.

    PubMed

    Kry, Stephen F; Popple, Richard; Molineu, Andrea; Followill, David S

    2012-01-01

    Ion recombination is approximately corrected for in the Task Group 51 protocol by Pion, which is calculated by a two-voltage measurement. This measurement approach may be a poor estimate of the true recombination, particularly if Pion is large (greater than 1.05). Concern exists that Pion in high-dose-per-pulse beams, such as flattening filter free (FFF) beams, may be unacceptably high, rendering the two-voltage measurement technique inappropriate. Therefore, Pion was measured for flattened beams of 6, 10, 15, and 18 MV and for FFF beams of 6 and 10 MV. The values for the FFF beams were verified with 1/V versus 1/Q curves (Jaffé plots). Pion was also measured for electron beams of 6, 12, 16, 18, and 20 MeV on a traditional accelerator, as well as on the high-dose-rate Varian TrueBeam accelerator. The measurements were made at a range of depths and with PTW, NEL, and Exradin Farmer-type chambers. Consistent with the increased dose per pulse, Pion was higher for FFF beams than for flattening filter beams. However, for all beams, measurement locations, and chambers examined, Pion never exceeded 1.018. Additionally, Pion was always within 0.3% of the recombination calculated from the Jaffé plots. We conclude that ion recombination can be adequately accounted for in high-dose-rate FFF beams using Pion determined with the standard two-voltage technique. PMID:23149774

  13. High-Dose Estradiol-Replacement Therapy Enhances the Renal Vascular Response to Angiotensin II via an AT2-Receptor Dependent Mechanism

    PubMed Central

    Safari, Tahereh; Nematbakhsh, Mehdi; Evans, Roger G.; Denton, Kate M.

    2015-01-01

    Physiological levels of estrogen appear to enhance angiotensin type 2 receptor- (AT2R-) mediated vasodilatation. However, the effects of supraphysiological levels of estrogen, analogous to those achieved with high-dose estrogen replacement therapy in postmenopausal women, remain unknown. Therefore, we pretreated ovariectomized rats with a relatively high dose of estrogen (0.5 mg/kg/week) for two weeks. Subsequently, renal hemodynamic responses to intravenous angiotensin II (Ang II, 30–300 ng/kg/min) were tested under anesthesia, while renal perfusion pressure was held constant. The role of AT2R was examined by pretreating groups of rats with PD123319 or its vehicle. Renal blood flow (RBF) decreased in a dose-related manner in response to Ang II. Responses to Ang II were enhanced by pretreatment with estradiol. For example, at 300 ng kg−1 min−1, Ang II reduced RBF by 45.7 ± 1.9% in estradiol-treated rats but only by 27.3 ± 5.1% in vehicle-treated rats. Pretreatment with PD123319 blunted the response of RBF to Ang II in estradiol-treated rats, so that reductions in RBF were similar to those in rats not treated with estradiol. We conclude that supraphysiological levels of estrogen promote AT2R-mediated renal vasoconstriction. This mechanism could potentially contribute to the increased risk of cardiovascular disease associated with hormone replacement therapy using high-dose estrogen. PMID:26681937

  14. High-dose chemotherapy and autologous stem cell support followed by posttransplantation doxorubicin as initial therapy for metastatic breast cancer.

    PubMed

    deMagalhaes-Silverman, M; Bloom, E; Lembersky, B; Lister, J; Pincus, S; Rybka, W; Voloshin, M; Wilson, J; Ball, E

    1997-02-01

    High-dose chemotherapy is associated with a high complete response rate and possibly some survival advantage in patients with metastatic breast cancer. We designed a clinical trial consisting of a two-step high-dose chemotherapy regimen followed by posttransplantation doxorubicin as the first chemotherapy treatment for metastatic disease. Twenty-one patients with metastatic breast cancer and no previous chemotherapy for metastatic disease were treated with high-dose cyclophosphamide (Cy; 5000 mg/m2), followed by granulocyte colony-stimulating factor. Peripheral blood stem cells were collected. Subsequently, patients received Cy (6000 mg/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb) with hematopoietic rescue. Upon recovery of hematopoietic and gastrointestinal toxicity, three cycles of doxorubicin (Dox; 60 mg/m2) were delivered. After Cy, nine patients (45%) developed neutropenic fevers. There were no episodes of bacteremia. Patients received CTCb 37 days after starting Cy and had a hospital stay of 19 days. After CTCb, the median number of days to an absolute neutrophil count >5 x 10(9)/liter was 8, and the median number of days to a platelet count >20 x 10(9)/liter was 9. Neutropenic fevers occurred in 12 patients. There were no hemorrhagic complications. Fifty-five of the 63 planned courses of Dox were delivered. The median time from peripheral blood stem cell infusion to the first Dox cycle was 38 days. The median time to the second Dox cycle was 28 days, and to the last cycle was 30 days. Three episodes of neutropenic fevers were observed. Two patients developed herpes zoster. This regimen is feasible, with acceptable toxicity. PMID:9815672

  15. Hypofractionated High-Dose Proton Beam Therapy for Stage I Non-Small-Cell Lung Cancer: Preliminary Results of A Phase I/II Clinical Study

    SciTech Connect

    Hata, Masaharu . E-mail: mhata@syd.odn.ne.jp; Tokuuye, Koichi; Kagei, Kenji; Sugahara, Shinji; Nakayama, Hidetsugu; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Mizumoto, Masashi; Ohara, Kiyoshi; Akine, Yasuyuki

    2007-07-01

    Purpose: To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm) in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites. Results: Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6-29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade {>=}3 was observed. Conclusions: Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC.

  16. A New Formulation of Calcitriol (DN-101) for High-Dose Pulse Administration in Prostate Cancer Therapy

    PubMed Central

    Henner, William David; Beer, Tomasz M

    2003-01-01

    Although the antineoplastic activity of calcitriol in prostate cancer has been known for many years, the agent’s use in oncology has been prevented because of the occurrence of hypercalcemia with daily administration. High-dose pulse administration of calcitriol has the potential to improve the therapeutic index of calcitriol. Results of a phase II study of calcitriol and docetaxel (Taxotere®) suggest that this combination may have utility in androgen-independent prostate cancer (AIPC). DN-101, a high-dose (15 μg) formulation of calcitriol suitable for use in oncology, is now being tested in a randomized trial (AIPC Study of Calcitriol Enhancing Taxotere). This formulation of calcitriol could become an important new tool for improving the efficacy of docetaxel in the treatment of AIPC and would join the ranks of other nuclear receptor ligands in cancer treatment. Investigations of DN-101 in the treatment of a broad range of tumor types and in combination with a variety of agents are an exciting new area of research. PMID:16985949

  17. A New Formulation of Calcitriol (DN-101) for High-Dose Pulse Administration in Prostate Cancer Therapy.

    PubMed

    Henner, William David; Beer, Tomasz M

    2003-01-01

    Although the antineoplastic activity of calcitriol in prostate cancer has been known for many years, the agent's use in oncology has been prevented because of the occurrence of hypercalcemia with daily administration. High-dose pulse administration of calcitriol has the potential to improve the therapeutic index of calcitriol. Results of a phase II study of calcitriol and docetaxel (Taxotere(R)) suggest that this combination may have utility in androgen-independent prostate cancer (AIPC). DN-101, a high-dose (15 mug) formulation of calcitriol suitable for use in oncology, is now being tested in a randomized trial (AIPC Study of Calcitriol Enhancing Taxotere). This formulation of calcitriol could become an important new tool for improving the efficacy of docetaxel in the treatment of AIPC and would join the ranks of other nuclear receptor ligands in cancer treatment. Investigations of DN-101 in the treatment of a broad range of tumor types and in combination with a variety of agents are an exciting new area of research. PMID:16985949

  18. Hyperthyroidism and radio-iodine therapy in a district general hospital.

    PubMed Central

    Child, D F; Mughni, M A; Hudson, P; Williams, C P; Harvey, J N

    1994-01-01

    A retrospective analysis was performed of 48 patients with hyperthyroidism (41 women aged 35-80, mean 56.6 years; 7 men aged 31-77, mean 52.1 years) treated with a fixed dose of 550 MBq 131I during a 12 month period May 1991-April 1992. Weight loss was common at presentation but 28.57% of women aged 35-49 years weighed over 80 kg compared to 9.98% in a standard UK population P < 0.05. Patients treated with carbimazole (73%) prior to 131I had higher FT3 levels at presentation (14.0 +/- 4.4 pmol/l) compared to those (27%) who were considered not to require such treatment (8.9 +/- 1.4 pmol/l, P < 0.001). Four months following radio-iodine, 67% were hypothyroid, 25% were euthyroid and 8% remained thyrotoxic and were retreated. Another patient became hypothyroid during 1 year of follow-up. Pre-treatment with carbimazole did not protect against the development of hypothyroidism (carbimazole treated 69% hypothyroid at 4 months, untreated 62% hypothyroid at 4 months). Patients with continuing thyrotoxicosis had very high FT3 levels at presentation (18.6, 21.1, 20 and in one patient reported only as > 10 pmol/l). A rationalized programme of follow-up assessments at 2, 3, 4, 8 and 12 months is suggested for patients treated with this dose of radio-iodine. PMID:7966101

  19. High-dose hepatitis B immunoglobulin therapy in hepatocellular carcinoma with hepatitis B virus-DNA/hepatitis B e antigen-positive patients after living donor liver transplantation

    PubMed Central

    Lee, Eung Chang; Kim, Seong Hoon; Lee, Seung Duk; Park, Hyeongmin; Lee, Soon-Ae; Park, Sang-Jae

    2016-01-01

    AIM: To investigate the impact of high-dose hepatitis B immunoglobulin (HBIG) on hepatocellular carcinoma (HCC) and hepatitis B virus (HBV) recurrence and overall survival after living donor liver transplantation (LDLT). METHODS: We investigated 168 patients who underwent LDLT due to HCC, and who were HBV-DNA/hepatitis B e antigen (HBeAg) -positive, from January 2008 to December 2013. After assessing whether the patients met the Milan criteria, they were assigned to the low-dose HBIG group and high-dose HBIG group. Using the propensity score 1:1 matching method, 38 and 18 pairs were defined as adhering to and not adhering to the Milan criteria. For each pair, HCC recurrence, HBV recurrence and overall survival were analyzed by the Kaplan-Meier method and the log rank test according to the HBIG dose. RESULTS: Among those who met the Milan criteria, the 6-mo, 1-year, and 3-year HCC recurrence-free survival rates were 88.9%, 83.2%, and 83.2% in the low-dose HBIG group and 97.2%, 97.2%, and 97.2% in the high-dose HBIG group, respectively (P = 0.042). In contrast, among those who did not meet the Milan criteria, HCC recurrence did not differ according to the HBIG dose (P = 0.937). Moreover, HBV recurrence and overall survival did not differ according to the HBIG dose among those who met (P = 0.317 and 0.190, respectively) and did not meet (P = 0.350 and 0.987, respectively) the Milan criteria. CONCLUSION: High-dose HBIG therapy can reduce HCC recurrence in HBV-DNA/HBeAg-positive patients after LDLT. PMID:27076765

  20. Reduction in relapse rate of radioiodine therapy in patients of toxic multinodular goiter: A quality improvement project

    PubMed Central

    Mitra, Sujata; Muthu, Sonai G

    2012-01-01

    Introduction: Radioiodine (I-131) therapy is the definitive treatment of toxic multinodular goiter (TMNG). Treatment failure may result in relapse after I-131 therapy. The present study was undertaken to reduce treatment failure rate of I-131 therapy in TMNG patients. Materials and Methods: Multiple causes may have lead to treatment failure of I-131 in TMNG patients making it difficult to establish a direct cause–effect relationship and take corrective action. Therefore, the JURAN methodology of quality improvement was applied. The treatment failure rate in 80 TMNG patients treated with I-131 in the period 2003–06 was 29%. The root cause analysis identified delay in decision to radioablate and concomitant antithyroid drugs (ATD) with I-131 therapy as factors leading to relapse. In 2007, a change in management was introduced with decision to radioablate all TMNG patients not remitting at 1 year of ATD and to withdraw ATD for 2 weeks prior to I-131 therapy. A total of 63 patients of TMNG followed the changed protocol between 2007 and 2009. Further analysis showed that one of the factors identified in the initial brainstorming (high iodide pool in the patient) had not been addressed in the protocol currently followed. The protocol was modified to include patient preparation and implemented after standardization. Results: The post-I-131 relapse rate in patients treated after implementation of the new protocol from 2007 to 2009 was 18% which further reduced to 16% in 2011 after modification of the protocol. Conclusion: The failure rate of I-131 therapy in TMNG reduced from 29% to 16% through standardization of the treatment procedure achieved by the use of Juran Methodology that helped to identify process-related defects. PMID:23599590

  1. Correlation of stress with outcome of radioiodine therapy for Graves disease

    SciTech Connect

    Stewart, T.; Rochon, J.; Lenfestey, R.; Wise, P.

    1985-06-01

    Between November 1965 and December 1983, 293 patients were treated for Graves disease using /sup 131/I. All patients were asked to identify a stressful event antedating the onset of overt clinical symptoms. Eighty-one patients were able to do this (27.6%). Two hundred forty-four patients received a single treatment, 49 required two or more treatments. Patients with stress initiating the symptoms of Graves disease became hypothyroid earlier, 50% at 12 mo compared with 36 mo for the nonstress group. At 10 yr 5% of the stress group remained euthyroid compared with 17% nonstress. The authors conclude that stress in the 12 mo or less before the onset of clinical symptoms potentiates the development of hypothyroidism induced by a standard dose of radioiodine.

  2. Effects of substitution and high-dose thyroid hormone therapy on deiodination, sulfoconjugation, and tissue thyroid hormone levels in prolonged critically ill rabbits.

    PubMed

    Debaveye, Yves; Ellger, Björn; Mebis, Liese; Visser, Theo J; Darras, Veerle M; Van den Berghe, Greet

    2008-08-01

    To delineate the metabolic fate of thyroid hormone in prolonged critically ill rabbits, we investigated the impact of two dose regimes of thyroid hormone on plasma 3,3'-diiodothyronine (T(2)) and T(4)S, deiodinase type 1 (D1) and D3 activity, and tissue iodothyronine levels in liver and kidney, as compared with saline and TRH. D2-expressing tissues were ignored. The regimens comprised either substitution dose or a 3- to 5- fold higher dose of T(4) and T(3), either alone or combined, targeted to achieve plasma thyroid hormone levels obtained by TRH. Compared with healthy animals, saline-treated ill rabbits revealed lower plasma T(3) (P=0.006), hepatic T(3) (P=0.02), and hepatic D1 activity (P=0.01). Substitution-dosed thyroid hormone therapy did not affect these changes except a further decline in plasma (P=0.0006) and tissue T(4) (P=0.04). High-dosed thyroid hormone therapy elevated plasma and tissue iodothyronine levels and hepatic D1 activity, as did TRH. Changes in iodothyronine tissue levels mimicked changes in plasma. Tissue T(3) and tissue T(3)/reverse T(3) ratio correlated with deiodinase activities. Neither substitution- nor high-dose treatment altered plasma T(2). Plasma T(4)S was increased only by T(4) in high dose. We conclude that in prolonged critically ill rabbits, low plasma T(3) levels were associated with low liver and kidney T(3) levels. Restoration of plasma and liver and kidney tissue iodothyronine levels was not achieved by thyroid hormone in substitution dose but instead required severalfold this dose. This indicates thyroid hormone hypermetabolism, which in this model of critical illness is not entirely explained by deiodination or by sulfoconjugation. PMID:18450965

  3. Randomized Phase II Trial of High-Dose Melatonin and Radiation Therapy for RPA Class 2 Patients With Brain Metastases (RTOG 0119)

    SciTech Connect

    Berk, Lawrence . E-mail: Berklb@moffitt.usf.edu; Berkey, Brian; Rich, Tyvin; Hrushesky, William; Gallagher, Michael; Kudrimoti, Mahesh; McGarry, Ronald C.; Suh, John; Mehta, Minesh

    2007-07-01

    Purpose: To determine if high-dose melatonin for Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) Class 2 patients with brain metastases improved survival over historical controls, and to determine if the time of day melatonin was given affected its toxicity or efficacy. RTOG 0119 was a phase II randomized trial for this group of patients. Methods and Materials: RTOG RPA Class 2 patients with brain metastases were randomized to 20 mg of melatonin, given either in the morning (8-9 AM) or in the evening (8-9 PM). All patients received radiation therapy (30 Gy in 10 fractions) in the afternoon. Melatonin was continued until neurologic deterioration or death. The primary endpoint was overall survival time. Neurologic deterioration, as reflected by the Mini-Mental Status Examination, was also measured. Results: Neither of the randomized groups had survival distributions that differed significantly from the historic controls of patients treated with whole-brain radiotherapy. The median survivals of the morning and evening melatonin treatments were 3.4 and 2.8 months, while the RTOG historical control survival was 4.1 months. Conclusions: High-dose melatonin did not show any beneficial effect in this group of patients.

  4. High-dose radiotherapy in inoperable nonsmall cell lung cancer: comparison of volumetric modulated arc therapy, dynamic IMRT and 3D conformal radiotherapy.

    PubMed

    Bree, Ingrid de; van Hinsberg, Mariëlle G E; van Veelen, Lieneke R

    2012-01-01

    Conformal 3D radiotherapy (3D-CRT) combined with chemotherapy for inoperable non-small cell lung cancer (NSCLC) to the preferable high dose is often not achievable because of dose-limiting organs. This reduces the probability of regional tumor control. Therefore, the surplus value of using intensity-modulated radiation therapy (IMRT) techniques, specifically volumetric modulated arc therapy (RapidArc [RA]) and dynamic IMRT (d-IMRT) has been investigated. RA and d-IMRT plans were compared with 3D-CRT treatment plans for 20 patients eligible for concurrent high-dose chemoradiotherapy, in whom a dose of 60 Gy was not achievable. Comparison of dose delivery in the target volume and organs at risk was carried out by evaluating 3D dose distributions and dose-volume histograms. Quality of the dose distribution was assessed using the inhomogeneity and conformity index. For most patients, a higher dose to the target volume can be delivered using RA or d-IMRT; in 15% of the patients a dose ≥60 Gy was possible. Both IMRT techniques result in a better conformity of the dose (p < 0.001). There are no significant differences in homogeneity of dose in the target volume. IMRT techniques for NSCLC patients allow higher dose to the target volume, thus improving regional tumor control. PMID:22459649

  5. Drug associated acute interstitial nephritis: clinical and pathological features and the response to high dose steroid therapy.

    PubMed

    Pusey, C D; Saltissi, D; Bloodworth, L; Rainford, D J; Christie, J L

    1983-01-01

    Nine episodes of drug associated acute interstitial nephritis, in seven patients, were treated between 1972 and 1980. The drugs implicated were cotrimoxazole (three times), ampicillin, Magnapen (ampicillin and flucloxacillin), penicillin, gentamicin, paracetamol and bendrofluazide. The time from exposure to the onset of symptoms ranged from one to 30 days. Presentation was with acute renal failure, which was non-oliguric in five cases, accompanied by rash (four), fever (four), and loin pain (two). Renal biopsy was carried out in all cases, and showed a characteristic interstitial infiltrate comprising substantial numbers of lymphocytes and plasma cells, with a variable number of neutrophils, eosinophils and histiocytes. Immunofluorescence was negative in all four cases studied in the acute phase, and showed scattered deposits of IgG, IgM, IgA and C3 on the tubular basement membrane in one patient during recovery. Significant proteinuria and an abnormal urine deposit were present in all cases, and seven of nine had radiological evidence of enlarged kidneys. Seven episodes were treated with high doses of methyl prednisolone and in all there was a response with a diuresis or spontaneous fall in serum creatinine within 72 hrs, and recovery of virtually normal renal function. Of two cases who did not initially receive steroids, one improved more slowly and one developed chronic renal impairment. PMID:6604293

  6. Diagnosis of prolactinoma in two male-to-female transsexual subjects following high-dose cross-sex hormone therapy.

    PubMed

    Cunha, F S; Domenice, S; Câmara, V L; Sircili, M H P; Gooren, L J G; Mendonça, B B; Costa, E M F

    2015-08-01

    Male-to-female transsexual persons use oestrogens + antiandrogens to adapt their physical bodies to the female sex. Doses are usually somewhat higher than those used by hypogonadal women receiving oestrogen replacement. Particularly in cases of self-administration of cross-sex hormones, doses may be very high. Oestrogens are powerful stimulators of synthesis and release of prolactin and serum prolactin levels are usually somewhat increased following oestrogen treatment. Prolactinomas have been reported in male-to-female transsexual persons, both after use of high and conventional doses of oestrogens but remain rare events. We report two new cases of prolactinomas in male-to-female transsexual persons, one in a 41-year-old subject who had used nonsupervised high-dose oestrogen treatment since the age of 23 years and another one in a 42 year old who had initiated oestrogen treatment at the age of 17 years. Their serum prolactin levels were strongly increased, and the diagnosis of a pituitary tumour was confirmed by imaging techniques. Both cases responded well to treatment with cabergoline treatment whereupon serum prolactin normalised. Our two cases are added to the three cases of prolactinomas in the literature in persons who had used supraphysiological doses of oestrogens. PMID:25059808

  7. Statin therapy and thromboxane generation in patients with coronary artery disease treated with high-dose aspirin.

    PubMed

    Bliden, K P; Singla, A; Gesheff, M G; Toth, P P; Tabrizchi, A; Ens, G; Guyer, K; Singh, M; Franzese, C J; Stapleton, D; Tantry, U S; Gurbel, P A

    2014-08-01

    Aspirin and statin therapy are mainstay treatments in patients with coronary artery disease (CAD). The relation between statin therapy, in vivo thromboxane (Tx) generation; a marker of inflammation, and blood thrombogenicity has never been explored. Urinary 11-dehydro (dh) TxB2 was determined in patients with suspected CAD on 325 mg daily aspirin therapy prior to undergoing cardiac catheterisation (n=281). Thrombogenicity was estimated by thrombelastographic measurement of thrombin-induced platelet-fibrin clot strength (TIP-FCS) and lipids/lipoproteins were determined by vertical density gradient ultracentrifugation/ELISA. The influence of statin therapy and dose was analysed by the atorvastatin equivalent dose (5-10 mg, 20-40 mg, or 80 mg daily). Statin therapy (n=186) was associated with a dose-dependent reduction in urinary 11-dh TxB2 (p=0.046) that was independent of LDL and apo B100 levels but was strongly related to TIP-FCS (p=0.006). By multivariate analysis, no statin therapy (n=95) and female gender were independently associated with high urinary 11-dh TxB2 [OR=2.95 (0.1.57-5.50, p=0.0007); OR=2.25 (1.24-4.05, p=0.007)], respectively. In aspirin-treated patients, statin therapy was independently and inversely associated with inflammation in a dose-dependent manner. Elevated 11-dh TxB2 was associated with a prothrombotic state indicated by high TIP-FCS. Our data suggest that measurement of urinary 11-dTxB2 may be a useful method to optimise statin dosing in order to reduce thrombotic risk. PMID:24763965

  8. High-Dose Daptomycin Therapy for Left-Sided Infective Endocarditis: a Prospective Study from the International Collaboration on Endocarditis

    PubMed Central

    Bayer, Arnold S.; Miró, Josè M.; Park, Lawrence P.; Guimarães, Armenio C.; Skoutelis, Athanasios; Fortes, Claudio Q.; Durante-Mangoni, Emanuele; Hannan, Margaret M.; Nacinovich, Francisco; Fernández-Hidalgo, Nuria; Grossi, Paolo; Tan, Ru-San; Holland, Thomas; Fowler, Vance G.; Corey, Ralph G.; Chu, Vivian H.

    2013-01-01

    The use of daptomycin in Gram-positive left-sided infective endocarditis (IE) has significantly increased. The purpose of this study was to assess the influence of high-dose daptomycin on the outcome of left-sided IE due to Gram-positive pathogens. This was a prospective cohort study based on 1,112 cases from the International Collaboration on Endocarditis (ICE)-Plus database and the ICE-Daptomycin Substudy database from 2008 to 2010. Among patients with left-sided IE due to Staphylococcus aureus, coagulase-negative staphylococci, and Enterococcus faecalis, we compared those treated with daptomycin (cohort A) to those treated with standard-of-care (SOC) antibiotics (cohort B). The primary outcome was in-hospital mortality. Time to clearance of bacteremia, 6-month mortality, and adverse events (AEs) ascribable to daptomycin were also assessed. There were 29 and 149 patients included in cohort A and cohort B, respectively. Baseline comorbidities did not differ between the two cohorts, except for a significantly higher prevalence of diabetes and previous episodes of IE among patients treated with daptomycin. The median daptomycin dose was 9.2 mg/kg of body weight/day. Two-thirds of the patients treated with daptomycin had failed a previous antibiotic regimen. In-hospital and 6-month mortalities were similar in the two cohorts. In cohort A, median time to clearance of methicillin-resistant S. aureus (MRSA) bacteremia was 1.0 day, irrespective of daptomycin dose, representing a significantly faster bacteremia clearance compared to SOC (1.0 versus 5.0 days; P < 0.01). Regimens with higher daptomycin doses were not associated with increased incidence of AEs. In conclusion, higher-dose daptomycin may be an effective and safe alternative to SOC in the treatment of left-sided IE due to common Gram-positive pathogens. PMID:24080644

  9. Brachial Plexus-Associated Neuropathy After High-Dose Radiation Therapy for Head-and-Neck Cancer

    SciTech Connect

    Chen, Allen M.; Hall, William H.; Li, Judy; Beckett, Laurel; Farwell, D. Gregory; Lau, Derick H.; Purdy, James A.

    2012-09-01

    Purpose: To identify clinical and treatment-related predictors of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer. Methods and Materials: Three hundred thirty patients who had previously completed radiation therapy for head-and-neck cancer were prospectively screened using a standardized instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from completion of radiation therapy was 56 months (range, 6-135 months). One-hundred fifty-five patients (47%) were treated by definitive radiation therapy, and 175 (53%) were treated postoperatively. Radiation doses ranged from 50 to 74 Gy (median, 66 Gy). Intensity-modulated radiation therapy was used in 62% of cases, and 133 patients (40%) received concurrent chemotherapy. Results: Forty patients (12%) reported neuropathic symptoms, with the most common being ipsilateral pain (50%), numbness/tingling (40%), motor weakness, and/or muscle atrophy (25%). When patients with <5 years of follow-up were excluded, the rate of positive symptoms increased to 22%. On univariate analysis, the following factors were significantly associated with brachial plexus symptoms: prior neck dissection (p = 0.01), concurrent chemotherapy (p = 0.01), and radiation maximum dose (p < 0.001). Cox regression analysis confirmed that both neck dissection (p < 0.001) and radiation maximum dose (p < 0.001) were independently predictive of symptoms. Conclusion: The incidence of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer may be underreported. In view of the dose-response relationship identified, limiting radiation dose to the brachial plexus should be considered when possible.

  10. Radioiodine Treatment and Thyroid Hormone Suppression Therapy for Differentiated Thyroid Carcinoma: Adverse Effects Support the Trend toward Less Aggressive Treatment for Low-Risk Patients

    PubMed Central

    Klein Hesselink, E.N.; Links, T.P.

    2015-01-01

    Over the past decades, the incidence of differentiated thyroid carcinoma (DTC) has steadily increased, with especially a growing number of low-risk patients. Whereas DTC used to be treated rather aggressively, it is now acknowledged that aggressive treatment does not affect outcome for low-risk patients and that it can induce adverse effects. In this review an overview of the most clinically relevant adverse effects of radioiodine treatment and thyroid hormone suppression therapy (THST) is presented, and the trend toward less aggressive treatment for low-risk patients is outlined. Salivary gland dysfunction occurs in roughly 30% of patients, and is probably due to the concentration of radioiodine in the salivary glands by the sodium/iodide symporter. Beta radiation from radioiodine can result in sialoadenitis and eventually fibrosis and loss of salivary function. Furthermore, patients can experience bone marrow dysfunction following radioiodine treatment. Although this is in general subclinical and transient, patients that receive very high cumulative radioiodine doses may be at risk for more severe bone marrow dysfunction. THST can induce adverse cardiovascular effects in patients with DTC, such as diastolic and systolic dysfunction, and also adverse vascular and prothrombotic effects have been described. Finally, the effects of THST on bone formation and resorption are outlined; especially postmenopausal women with DTC on THST seem to be at risk of bone loss. In the past years, advances have been made in preventing low-risk patients from being overtreated. Improved biomarkers are still needed to further optimize risk stratification and personalize medicine. PMID:26279993

  11. Clinical Outcome of Radioiodine Therapy in Low-intermediate Risk Papillary Thyroid Carcinoma with BRAF(V600E) Mutation.

    PubMed

    Jiao, L I; Tao, Yang; Teng, Zhao; Jun, Liang; Yan-Song, Lin

    2016-06-10

    Objective To evaluate the impact of BRAF(V600E) gene status on clinical outcome of radioiodine((131)I) therapy in low-intermediate risk recurrent papillary thyroid carcinoma (PTC). Methods Totally 135 PTC patients were enrolled and divided into two groups according to BRAF(V600E) gene status:BRAF(V600E) mutation group(n=105) and BRAF(V600E) wild group(n=30). The median follow-up time was 2.16 years(1.03-4.06 years),and clinical outcome after initial (131)I ablation therapy was divided into excellent response(ER),acceptable response(AR),and incomplete response(IR) according to the serological and imageological follow-up results. The cinical outcomes were then compared between these two groups. Results There was no significant difference in clinicopathological features and initial radioactive iodine dose between BRAF(V600E) mutation and wild groups (P>0.05). ER,AR,and IR after (131)I ablation therapy accounted for 74.3%,20.0%,and 5.7% in BRAF(V600E) mutation group and 73.3%,20.0%,and 6.7% in BRAF(V600E) wild group,and no statistical difference was found (P=0.891). Conclusion For low-intermediate risk recurrent PTC,BRAF(V600E) gene status may have no impact on the response to (131)I ablation therapy,and thus this molecular feature should not be used as an independent weighting factor for risk assessment in this population. PMID:27544995

  12. [A case of advanced breast cancer with multiple bone metastases responding to docetaxel and high-dose toremifene as fourth-line chemo-endocrine therapy].

    PubMed

    Minamoto, Kanji; Ikeda, Toshio

    2009-12-01

    A 55-year old woman, who underwent left mastectomy (Bt+Ax), was revealed to have sternum metastasis by postoperative 99mTc bone scanning(T1bN1M1). She received daily aromatase inhibitor (anastrozole), as a primary systemic endocrine therapy, and biweekly pamidronate for metastatic breast cancer. However, she depended on folk medicine a year later, at which time the primary treatment was discontinued. Another year later, the bone metastases developed with increased serum levels of tumor markers (CEA, CA19-9, and NCC-ST-439). Then, she underwent three different regimens of systemic chemo-endocrine therapy over the following three years, including CAF+MPA as the first-line, paclitaxel (PTX) + anastrozole as the second-line, and S-1+anastrozole as the third-line regimen. She recently completed 10 courses of the fourth-line regimen[tri-weekly docetaxel (DOC) and high-dose toremifene (TOR 120 mg/day)], which reduced levels of 99mTc accumulation in the multiple bone metastases and levels of the serum tumor markers to the normal range. No severe adverse events occurred except peripheral thrombovasculitis (grade 2) in her left anterior arm during the fourth regimen. She recently maintains the current status by taking a regular dose (40 mg/day) of toremifene for 5 months. Combination treatment with DOC and high-dose TOR can be one of the worthwhile regimens as systemic chemo-endocrine therapy for patients with advanced breast cancer who develop bone metastases. PMID:20009468

  13. Salvage therapy with high dose Intravenous Immunoglobulins in acquired Von Willebrand Syndrome and unresponsive severe intestinal bleeding

    PubMed Central

    2014-01-01

    A 91-year-old woman affected with acquired Von Willebrand (VW) syndrome and intestinal angiodysplasias presented with severe gastrointestinal bleeding (hemoglobin 5 g/dl). Despite replacement therapy with VW factor/factor VIII concentrate qid, bleeding did not stop (eleven packed red blood cell units were transfused over three days). High circulating levels of anti-VW factor immunoglobulin M were documented immunoenzimatically. Heart ultrasound showed abnormalities of the mitral and aortic valves with severe flow alterations. When intravenous immunoglobulins were added to therapy, prompt clinical and laboratory responses occurred: complete cessation of bleeding, raise in hemoglobin, VW factor antigen, VW ristocetin cofactor and factor VIII levels as well as progressive reduction of the anti-VWF autoantibody levels. PMID:24926417

  14. Phase 2 Trial of Hypofractionated High-Dose Intensity Modulated Radiation Therapy With Concurrent and Adjuvant Temozolomide for Newly Diagnosed Glioblastoma

    SciTech Connect

    Iuchi, Toshihiko; Hatano, Kazuo; Kodama, Takashi; Sakaida, Tsukasa; Yokoi, Sana; Kawasaki, Koichiro; Hasegawa, Yuzo; Hara, Ryusuke

    2014-03-15

    Purpose/Objectives: To assess the effect and toxicity of hypofractionated high-dose intensity modulated radiation therapy (IMRT) with concurrent and adjuvant temozolomide (TMZ) in 46 patients with newly diagnosed glioblastoma multiforme (GBM). Methods and Materials: All patients underwent postsurgical hypofractionated high-dose IMRT. Three layered planning target volumes (PTVs) were contoured. PTV1 was the surgical cavity and residual tumor on T1-weighted magnetic resonance images with 5-mm margins, PTV2 was the area with 15-mm margins surrounding the PTV1, and PTV3 was the high-intensity area on fluid-attenuated inversion recovery images. Irradiation was performed in 8 fractions at total doses of 68, 40, and 32 Gy for PTV1, PTV2, and PTV3, respectively. Concurrent TMZ was given at 75 mg/m{sup 2}/day for 42 consecutive days. Adjuvant TMZ was given at 150 to 200 mg/m{sup 2}/day for 5 days every 28 days. Overall and progression-free survivals were evaluated. Results: No acute IMRT-related toxicity was observed. The dominant posttreatment failure pattern was dissemination. During a median follow-up time of 16.3 months (range, 4.3-80.8 months) for all patients and 23.7 months (range, 12.4-80.8 months) for living patients, the median overall survival was 20.0 months after treatment. Radiation necrosis was diagnosed in 20 patients and was observed not only in the high-dose field but also in the subventricular zone (SVZ). Necrosis in the SVZ was significantly correlated with prolonged survival (hazard ratio, 4.08; P=.007) but caused deterioration in the performance status of long-term survivors. Conclusions: Hypofractionated high-dose IMRT with concurrent and adjuvant TMZ altered the dominant failure pattern from localized to disseminated and prolonged the survival of patients with GBM. Necrosis in the SVZ was associated with better patient survival, but the benefit of radiation to this area remains controversial.

  15. The Sonographic Features of the Thyroid Gland After Treatment with Radioiodine Therapy in Patients with Graves' Disease.

    PubMed

    English, Collette; Casey, Ruth; Bell, Marcia; Bergin, Diane; Murphy, Joseph

    2016-01-01

    The aim of the study was to describe the typical sonographic features of the thyroid gland in patients with Graves' hyperthyroidism after radioiodine therapy (RIT). Thirty patients (21 female and 9 male) with a mean age of 53 y (standard deviation [SD] ± 11.3) and with previous Graves' disease who had been successfully treated with RIT were enrolled in the study. All were hypothyroid or euthyroid after treatment. The thyroid ultrasound was carried out by a single experienced operator with an 8-MHz linear transducer. Volume, vascularity, echogenicity and echotexture of the glands were noted. The presence of nodules and lymph nodes was also documented. The mean volumes of the right lobe were 2.4 mL ± 2.9 SD (0.6-14) and the left lobe were 1.8 mL ± 1.9 SD (0.4-9.1), with a mean total volume of 4.2 mL ± 4.7 SD (1.3-19.1). Of those who had a pre-treatment ultrasound (23%), the percentage reduction in volume was 87% (p < 0.05); 93% of the glands were hypovascular, with the remaining 7% showing normal vascularity. The glands were hyperechoic and of coarse echotexture. Overall, the sonographic features of the post-RIT gland included a significantly reduced mean total volume of 4.2 mL, hypovascularity, coarse echotexture and hyperechogenicity. PMID:26603660

  16. Prognostic Factors of the Efficacy of High-dose Corticosteroid Therapy in Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome During Pregnancy: A Meta-analysis.

    PubMed

    Yang, Li; Ren, Chenchen; Mao, Minhong; Cui, Shihong

    2016-03-01

    The aim of this study was to identify the factors which can affect the efficacy of corticosteroid (CORT) therapy in the management of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome.Research articles reporting the efficacy of CORT therapy to HELLP syndrome patients were searched in several electronic databases including EMBASE, Google Scholar, Ovid SP, PubMed, and Web of Science. Study selection was based on predefined eligibility criteria. Efficacy was defined by the changes from baseline in HELLP syndrome indicators after CORT therapy. Meta-analyses were carried out with Stata software.Data of 778 CORT-treated HELLP syndrome patients recruited in 22 studies were used in the analyses. Corticosteroid treatment to HELLP syndrome patients was associated with significant changes from baseline in platelet count; serum levels of aspartate aminotransaminase, alanine transaminase, and lactic dehydrogenase (LDH); mean blood pressure; and urinary output. Lower baseline platelet count predicted higher change in platelet count after CORT therapy. Lower baseline platelet count and lower baseline urinary output predicted greater changes in LDH levels after CORT therapy. There was also an inverse relationship between the change from baseline in LDH levels and intensive care duration. Higher CORT doses were associated with greater declines in the aspartate aminotransaminase, alanine transaminase, and LDH levels. Incidence of cesarean delivery was inversely associated with the gestation age. The percentage of nulliparous women had a positive association with the intensive care stay duration.High-dose CORT therapy to HELLP syndrome patients provides benefits in improving disease markers and reducing intensive care duration, especially in cases such as mothers with much lower baseline platelet count and LDH levels. PMID:27043683

  17. Prognostic Factors of the Efficacy of High-dose Corticosteroid Therapy in Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome During Pregnancy

    PubMed Central

    Yang, Li; Ren, Chenchen; Mao, Minhong; Cui, Shihong

    2016-01-01

    Abstract The aim of this study was to identify the factors which can affect the efficacy of corticosteroid (CORT) therapy in the management of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Research articles reporting the efficacy of CORT therapy to HELLP syndrome patients were searched in several electronic databases including EMBASE, Google Scholar, Ovid SP, PubMed, and Web of Science. Study selection was based on predefined eligibility criteria. Efficacy was defined by the changes from baseline in HELLP syndrome indicators after CORT therapy. Meta-analyses were carried out with Stata software. Data of 778 CORT-treated HELLP syndrome patients recruited in 22 studies were used in the analyses. Corticosteroid treatment to HELLP syndrome patients was associated with significant changes from baseline in platelet count; serum levels of aspartate aminotransaminase, alanine transaminase, and lactic dehydrogenase (LDH); mean blood pressure; and urinary output. Lower baseline platelet count predicted higher change in platelet count after CORT therapy. Lower baseline platelet count and lower baseline urinary output predicted greater changes in LDH levels after CORT therapy. There was also an inverse relationship between the change from baseline in LDH levels and intensive care duration. Higher CORT doses were associated with greater declines in the aspartate aminotransaminase, alanine transaminase, and LDH levels. Incidence of cesarean delivery was inversely associated with the gestation age. The percentage of nulliparous women had a positive association with the intensive care stay duration. High-dose CORT therapy to HELLP syndrome patients provides benefits in improving disease markers and reducing intensive care duration, especially in cases such as mothers with much lower baseline platelet count and LDH levels. PMID:27043683

  18. High-Dose Split-Course Radiation Therapy for Anal Cancer: Outcome Analysis Regarding the Boost Strategy (CORS-03 Study)

    SciTech Connect

    Hannoun-Levi, Jean-Michel; Ortholan, Cecile; Resbeut, Michel; Teissier, Eric; Ronchin, Philippe; Cowen, Didier; Zaccariotto, Audrey; Benezery, Karen; Francois, Eric; Salem, Naji; Ellis, Steve; Azria, David; Gerard, Jean-Pierre

    2011-07-01

    Purpose: To retrospectively assess the clinical outcome in anal cancer patients treated with split-course radiation therapy and boosted through external-beam radiation therapy (EBRT) or brachytherapy (BCT). Methods and Materials: From January 2000 to December 2004, a selected group (162 patients) with invasive nonmetastatic anal squamous cell carcinoma was studied. Tumor staging reported was T1 = 31 patients (19%), T2 = 77 patients (48%), T3 = 42 patients (26%), and T4= 12 patients (7%). Lymph node status was N0-1 (86%) and N2-3 (14%). Patients underwent a first course of EBRT: mean dose 45.1 Gy (range, 39.5-50) followed by a boost: mean dose 17.9 Gy (range, 8-25) using EBRT (76 patients, 47%) or BCT (86 patients, 53%). All characteristics of patients and tumors were well balanced between the BCT and EBRT groups. Results: The mean overall treatment time (OTT) was 82 days (range, 45-143) and 67 days (range, 37-128) for the EBRT and BCT groups, respectively (p < 0.001). The median follow-up was 62 months (range, 2-108). The 5-year cumulative rate of local recurrence (CRLR) was 21%. In the univariate analysis, the prognostic factors for CRLR were as follows: T stage (T1-2 = 15% vs. T3-4 = 36%, p = 0.03), boost technique (BCT = 12% vs. EBRT = 33%, p = 0.002) and OTT (OTT <80 days = 14%, OTT {>=}80 days = 34%, p = 0.005). In the multivariate analysis, BCT boost was the unique prognostic factor (hazard ratio = 0.62 (0.41-0.92). In the subgroup of patients with OTT <80 days, the 5-year CRLR was significantly increased with the BCT boost (BC = 9% vs. EBRT = 28%, p = 0.03). In the case of OTT {>=}80 days, the 5-year CRLR was not affected by the boost technique (BCT = 29% vs. EBRT = 38%, p = 0.21). Conclusion: In anal cancer, when OTT is <80 days, BCT boost is superior to EBRT boost for CRLR. These results suggest investigating the benefit of BCT boost in prospective trials.

  19. Hypofractionated High-Dose Radiation Therapy for Prostate Cancer: Long-Term Results of a Multi-Institutional Phase II Trial

    SciTech Connect

    Fonteyne, Valerie; Soete, Guy; Arcangeli, Stefano; De Neve, Wilfried; Rappe, Bernard; Storme, Guy; Strigari, Lidia; Arcangeli, Giorgio; De Meerleer, Gert

    2012-11-15

    Purpose: To report late gastrointestinal (GI) and genitourinary (GU) toxicity, biochemical and clinical outcomes, and overall survival after hypofractionated radiation therapy for prostate cancer (PC). Methods and Materials: Three institutions included 113 patients with T1 to T3N0M0 PC in a phase II study. Patients were treated with 56 Gy in 16 fractions over 4 weeks. Late toxicity was scored using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria extended with additional symptoms. Biochemical outcome was reported according to the Phoenix definition for biochemical failure. Results: The incidence of late GI and GU toxicity was low. The 3-year actuarial risk of developing late GU and GI toxicity of grade {>=}2 was 13% and 8% respectively. Five-year biochemical non-evidence of disease (bNED) was 94%. Risk group, T stage, and deviation from planned hormone treatment were significant predictive factors for bNED. Deviation from hormone treatment remained significant in multivariate analysis. Five-year clinical non evidence of disease and overall survival was 95% and 91% respectively. No patient died from PC. Conclusions: Hypofractionated high-dose radiation therapy is a valuable treatment option for patients with PC, with excellent biochemical and clinical outcome and low toxicity.

  20. High-dose cytarabine as salvage therapy for relapsed or refractory acute myeloid leukemia-is more better or more of the same?

    PubMed

    Wolach, Ofir; Itchaki, Gilad; Bar-Natan, Michal; Yeshurun, Moshe; Ram, Ron; Herscovici, Corina; Shpilberg, Ofer; Douer, Dan; Tallman, Martin S; Raanani, Pia

    2016-03-01

    Cytarabine is the backbone of most chemotherapeutic regimens for acute myeloid leukemia (AML), yet the optimal dose for salvage therapy of refractory or relapsed AML (RR-AML) has not been established. Very high dose single-agent cytarabine at 36 g/m(2) (ARA-36) was previously shown to be effective and tolerable in RR-AML. In this retrospective analysis, we aim to describe the toxicity and efficacy of ARA-36 as salvage therapy for patients with AML who are primary refractory to intensive daunorubicin-containing induction or those relapsing after allogeneic stem cell transplant (alloSCT). Fifteen patients, median age 53 years, were included in the analysis. Six patients were treated for induction failure, one had resistant APL, and eight relapsed after alloSCT. Complete remission was achieved in 60% of patients. Surviving patients were followed for a median of 8.5 months. One-year overall survival was 54% (95% CI 30%-86%), and relapse rate from remission (n = 9) was 56%. Grade III/IV pulmonary, infectious, ocular and gastrointestinal toxicities occurred in 26%, 20%, 20% and 20% of patients respectively. Salvage therapy with ARA-36 regimen for RR-AML has considerable efficacy with manageable toxicity in patients with induction failure or post-transplant relapse. Overall survival in these high-risk patients still remains poor. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25689584

  1. Use of PET for estimation of radiation dose variations within the thyroid from radioiodine therapy in thyrotoxic patients

    SciTech Connect

    Ott, R.J.; Batty, V.; Clack, R.; Flower, M.A.; Leach, M.O.; Marsden, P.; McCready, V.R.; Webb, S.

    1985-05-01

    A series of 22 patients have been studied using a prototype Multiwire Proportional Chamber Positron Camera to determine the accuracy of measurement of thyroid uptake of radioiodine. The patients being treated for thyrotoxicosis were given a solution containing 1.5 mCi of I-131 and 0.7 mCi of I-124. In a few case 0.3 mCi of I-124 was given prior to I-131 therapy. Data acquisition consisted of 8 contiguous views of the thyroid covering the full 360 degrees around the patient. Each study contained approximately 400,000 events. Data analysis consisted of a simple backprojection and 3D deconvolution of the point source response function to produce a 64x64x64 volume matrix using 0.27ml voxels. The volume of the thyroid was obtained using a simple thresholding technique to determine the number of voxels within the thyroid. Phantom measurements show that the functional volume and hence the radiation dose to the thyroid can be estimated to approx. =10%. From conventional imaging with a gamma camera plus pinhole collimator, 18 out of 22 patients were diagnosed as having uniform Graves disease. The high resolution tomographic information provided by PET imaging has shown that the uptake in 5 of these 18 patients was multinodular. In one case the volume of the nodules within the thyroid was estimated to be 45% of the organ volume. This non-uniform uptake of iodine within the thyroid has consequences for the overall management of hyperthyroidism in patients thought to have Graves disease. It may in part explain the cases of unexpected post therapy hypothyroidism.

  2. Ineffectiveness of daily standard and high-dose antiviral therapy in preventing short episodes of genital HSV-2 reactivation: three randomized, open-label cross-over trials

    PubMed Central

    Johnston, Christine; Saracino, Misty; Kuntz, Steve; Magaret, Amalia; Selke, Stacy; Huang, Meei-li; Schiffer, Joshua T.; Koelle, David M.; Corey, Lawrence; Wald, Anna

    2012-01-01

    Background Recent studies indicate that short subclinical episodes of herpes simplex virus type 2 (HSV-2) are the predominant form of skin and mucosal viral shedding. We evaluated whether standard or high-dose antiviral therapy reduced the frequency of such shedding. Methods To determine whether short episodes of genital HSV shedding are suppressed on standard dose (SD) and high-dose (HD) antiviral therapy, HSV-2 seropositive, HIV seronegative persons in Seattle, WA were enrolled into three separate but complementary randomized, open-label, cross-over studies comparing 1) no medication to aciclovir 400 mg twice daily (SD-ACV), 2) valaciclovir 500 mg daily (SD-VAL) to aciclovir 800 mg three times daily (TID) (HD-ACV), and 3) SD-VAL to HD-VAL (1 gm TID). Study arms lasted 4–7 weeks, separated by one week wash-out. Participants obtained genital swabs four times daily for quantitative HSV DNA PCR. The primary endpoint was within-person comparison of shedding rate on each study arm. Results Of 113 participants randomized, 90 were eligible for analysis of the primary endpoint. Participants collected 23,605 swabs; of these 1272 (5·4%) had HSV detected. HSV shedding was significantly higher during the no medication arm (18·1% of swabs) compared with SD-ACV (1.2% of swabs, IRR=0·05, 95% CI=0·03–0·08). Breakthrough reactivations occurred on all doses (SD-ACV 1·2%, SD-VAL 5·2%, HD-ACV 4·2%, and HD-VAL 3·3% of swabs). HD-VAL was associated with less shedding compared with SD-VAL (IRR=0·54, 95% CI=0·44–0·66), likely due to more rapid clearance of mucosal HSV (4·7 logs/6 hours on HD-VAL vs. 4·4 logs/6 hours on SD-VAL, (p=0·02)). However, the annualized breakthrough episodes was similar on SD-VAL (22·6) and HD-ACV (20·2, p=0·54) and SD-VAL (14.9) and HD-VAL (16·5, p=0·34). Regardless of dose, breakthrough episodes were short (median 7–10 hours) and 80% were subclinical. Studies were not designed to make inter-trial comparisons between antiviral doses

  3. A novel treatment planning methodology for high dose (166)Ho-DOTMP therapy in patients with multiple myeloma

    NASA Astrophysics Data System (ADS)

    McCullough, Steven Patrick

    2000-09-01

    patient without irrigation, will not significantly reduce the bladder wall dose. The results from this work will produce the most advanced treatment planning methodology for bone marrow ablation therapy using radioisotopes currently available. Treatments can be tailored specifically for each patient, including the addition of concomitant total body irradiation for patients with unfavorable dose distributions, to deliver a desired patient disease response, while minimizing the dose or toxicity to non- target organs.

  4. A Prospective Exploratory Analysis of Cardiac Biomarkers and Electrocardiogram Abnormalities in Patients Receiving Thoracic Radiation Therapy with High-Dose Heart Exposure

    PubMed Central

    Gomez, Daniel R.; Yusuf, Syed Wamique; Munsell, Mark; Welsh, James W.; Liao, Zhongxing; Lin, Steven H.; Pan, Hubert; Chang, Joe Y.; Komaki, Ritsuko; Cox, James D.; McAleer, Mary Frances; Grosshans, David R.

    2014-01-01

    Introduction Acute effects of incidental cardiac irradiation in patients treated for thoracic cancer are not well characterized. We evaluated longitudinal changes in cardiac biomarkers for patients undergoing conformal radiation therapy (RT) with thoracic malignancies with high-dose cardiac exposure. Methods Twenty-five patients enrolled in a prospective trial (February 2009–December 2012) received ≥45 Gy to the thorax, with pretreatment estimates of ≥20 Gy to the heart. Chemotherapy was allowed except for doxorubicin or fluorouracil. Electrocardiographic (ECG), troponin-I (TnI), and brain natriuretic peptide (BNP) measurements were obtained before RT, within 24 hours of the first fraction, at the end of RT, and at first follow-up (1–2 months). These biomarkers were quantified at specific times and changes from baseline were evaluated with paired t tests. Results The median heart dose was 25.9 Gy (range 10.1–35.1 Gy). After the first RT fraction, no changes were noted in ECG or median Tnl or BNP levels; at the end of RT, two patients had elevated TnI and BNP, but neither difference was statistically significant. At first follow-up, TnI had returned to normal but the median BNP remained elevated (P=0.042). BNP did not increase over time in the 18 patients who received only RT. Twelve patients experienced acute ECG changes during RT, which resolved in seven patients by the next measurement. No patients experienced clinically significant RT-related events. Conclusion Increases in BNP and ECG changes were observed during high doses of radiation to the heart. The findings of this pilot study warrant further investigation and validation. PMID:25521400

  5. Combined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer cells.

    PubMed

    Chatterjee, Sushmita; Thaker, Nirmal; De, Abhijit

    2015-01-01

    Radiosensitization using either metformin or 2-deoxy-d-glucose (2-DG) in various cancer cells has been reported. The present study reveals novel information on combining these drugs to enhance radiosensitization effect in breast cancer (BC) cells. Responses to low-dose Cobalt60 radiation, as well as a newly emerged radioiodine therapy target for BC, that is, sodium-iodide symporter (NIS or SLC5A5) protein, are tested. As therapeutic potential of NIS in BC is often limited due to low uptake and fast efflux rate of iodine, the scope of these two radiosensitizers to further improve NIS-mediated (131)I therapeutic efficacy is explored. Two BC cell lines, MCF-7, and MDA MB231 are tested to optimize minimal drug doses required for radiosensitization. A combination of 2 mM metformin and 20 mM 2-DG with 2 grey (Gy) Cobalt60 radiation shows significant radiosensitization effect (P=0.0002). In cells treated with the combination therapy, increased γH2A.X foci formation was noted. Further, MCF-7 BC cells overexpressing NIS (MCF-7 NIS) was established, and using the optimized drug concentrations, significant radiosensitization (P=0.0019) by 50 μ Ci (131)I usage was found to be the case as well. Apoptosis data corroborates with the result of clonogenic assay showing significant increase in apoptotic population upon dual drug-mediated radiosensitization. In case of metformin treatment, lowered adenosine triphosphate (ATP) content of the cell has been observed. The encouraging radiosensitization effect observed using combined 2-DG and metformin may aid in reducing Cobalt60 radiation exposure or for targeted radioiodine therapy in BC cells with NIS expression. This study indicates high potential of this drug combination in sensitizing BC cells for NIS-mediated-targeted radioiodine therapy, which otherwise may have lacked efficacy. PMID:26355636

  6. Retrospective Analysis of the Safety and Efficacy of High-dose Interleukin-2 After Prior Tyrosine Kinase Inhibitor Therapy in Patients With Advanced Renal Cell Carcinoma

    PubMed Central

    Wong, Michael K. K.; Agarwal, Neeraj; Redman, Bruce G.; Logan, Theodore; Gao, Dexiang; Flaig, Thomas W.; Lewis, Karl; Poust, Jamie; Monk, Paul; Jarkowski, Anthony; Sendilnathan, Arun; Bolden, Marcus; Kuzel, Timothy M.; Olencki, Thomas

    2014-01-01

    Although tyrosine kinase inhibitors (TKI) are the most common first-line therapy for metastatic renal cell carcinoma, high-dose interleukin-2 (HD-IL2) remains the only agent that provides durable complete responses. The optimal sequence of these agents remains uncertain. This retrospective multi-institutional study examined the safety and efficacy of HD-IL2 following TKI therapy. After IRB approval at 7 HD-IL2 centers, data relating to patient, disease, and treatment characteristics among 40 consecutive patients with metastatic renal cell carcinoma who were treated with HD-IL2 after at least 1 prior TKI therapy were retrospectively collected. The most common cardiac adverse events were grade 3 hypotension and vascular leak syndrome. Six patients (15%) experienced other grade ≥3 cardiac adverse events. There were 2 treatment-related deaths due to congestive heart failure, occurring in 1 patient with short TKI to HD-IL2 interval and another patient with an abnormal baseline cardiac stress test. Best responses included 2 CRs (5%, duration 40+ and 62+ mo), 3 PRs (8%, duration 6, 11, and 24 mo), 13 SD (32%, median duration 12 mo), 20 PD (50%), and 2 not evaluable patients. Median overall survival was 22 months. Administration of HD-IL2 could be safe and effective after TKI therapy; however, careful selection of patients is critical. We recommend baseline cardiac risk factor assessment, screening with both cardiac stress test and echocardiogram, and allowing a TKI to HD-IL2 interval of at least 2 months. PMID:25075565

  7. Retrospective analysis of the safety and efficacy of high-dose interleukin-2 after prior tyrosine kinase inhibitor therapy in patients with advanced renal cell carcinoma.

    PubMed

    Lam, Elaine T; Wong, Michael K K; Agarwal, Neeraj; Redman, Bruce G; Logan, Theodore; Gao, Dexiang; Flaig, Thomas W; Lewis, Karl; Poust, Jamie; Monk, Paul; Jarkowski, Anthony; Sendilnathan, Arun; Bolden, Marcus; Kuzel, Timothy M; Olencki, Thomas

    2014-09-01

    Although tyrosine kinase inhibitors (TKI) are the most common first-line therapy for metastatic renal cell carcinoma, high-dose interleukin-2 (HD-IL2) remains the only agent that provides durable complete responses. The optimal sequence of these agents remains uncertain. This retrospective multi-institutional study examined the safety and efficacy of HD-IL2 following TKI therapy. After IRB approval at 7 HD-IL2 centers, data relating to patient, disease, and treatment characteristics among 40 consecutive patients with metastatic renal cell carcinoma who were treated with HD-IL2 after at least 1 prior TKI therapy were retrospectively collected. The most common cardiac adverse events were grade 3 hypotension and vascular leak syndrome. Six patients (15%) experienced other grade ≥3 cardiac adverse events. There were 2 treatment-related deaths due to congestive heart failure, occurring in 1 patient with short TKI to HD-IL2 interval and another patient with an abnormal baseline cardiac stress test. Best responses included 2 CRs (5%, duration 40+ and 62+ mo), 3 PRs (8%, duration 6, 11, and 24 mo), 13 SD (32%, median duration 12 mo), 20 PD (50%), and 2 not evaluable patients. Median overall survival was 22 months. Administration of HD-IL2 could be safe and effective after TKI therapy; however, careful selection of patients is critical. We recommend baseline cardiac risk factor assessment, screening with both cardiac stress test and echocardiogram, and allowing a TKI to HD-IL2 interval of at least 2 months. PMID:25075565

  8. Treatment with lithium prevents serum thyroid hormone increase after thionamide withdrawal and radioiodine therapy in patients with Graves' disease.

    PubMed

    Bogazzi, Fausto; Bartalena, Luigi; Campomori, Alberto; Brogioni, Sandra; Traino, Claudio; De Martino, Fabio; Rossi, Giuseppe; Lippi, Francesco; Pinchera, Aldo; Martino, Enio

    2002-10-01

    Serum thyroid hormone concentrations increase after radioiodine (RAI) therapy for Graves' disease. This phenomenon has been ascribed to either antithyroid drug withdrawal before RAI therapy or release of preformed thyroid hormones into the bloodstream from the RAI-damaged thyroid. Lithium blocks the release of iodine and thyroid hormones from the thyroid, thus enhancing the effectiveness of RAI therapy. Changes in serum-free thyroxine (FT4) and triiodothyronine (FT3) levels after methimazole (MMI) discontinuation and RAI therapy were evaluated in a prospective, randomized, control study of 36 patients with Graves' disease. After a 3- to 4-month course of MMI, patients were assigned to one of three groups: G1 (RAI alone); G2 (RAI plus lithium for 6 d starting on the day of RAI therapy); or G3 (RAI plus lithium for 19 d starting on the day of MMI withdrawal). G1-G2 patients had an increase in serum FT4 and FT3 levels from 13.5 +/- 6.5 to 19.8 +/- 9.2 pmol/liter and 5.0 +/- 2.0 to 8.0 +/- 4.8 pmol/liter, respectively (P < 0.0001), 2-5 d after MMI withdrawal, but G3 patients showed no changes. In the 30 d after RAI therapy, mean serum FT4 values increased in G1 patients (P = 0.02), peaking at 3-7 d (P < 0.05) but not in G2 and G3 patients. Serum FT3 levels decreased in G1, G2, and G3 (P = 0.03, P = 0.001, P = 0.02, respectively). Hyperthyroidism was cured in 8 of 12 G1 patients, 11 of 12 G2 patients, and 11 of 12 G3 patients (P = 0.31). Control of hyperthyroidism was prompter in G2 (P = 0.08) and G3 (P < 0.05) than in G1 patients. Patients in the three groups received a similar dose of RAI, but the committed radiation to the thyroid was higher in G3 (563 +/- 174 Gray) and G2 (588 +/- 347 Gray) than in G1 (429 +/- 204 Gray) (P < 0.03). In conclusion, the results of the present study demonstrate that: 1) MMI withdrawal is associated with a slight rise in serum thyroid hormone levels; 2) a further increase occurs after RAI therapy; 3) changes in serum thyroid hormone

  9. Is robotic arm stereotactic body radiation therapy “virtual high dose ratebrachytherapy” for prostate cancer? An analysis of comparative effectiveness using published data [corrected].

    PubMed

    Zaorsky, Nicholas George; Hurwitz, Mark D; Dicker, Adam P; Showalter, Timothy N; Den, Robert B

    2015-05-01

    High-dose rate brachytherapy (HDR-BT) monotherapy and robotic arm (i.e., CyberKnife) stereotactic body radiation therapy (SBRT) are emerging technologies that have become popular treatment options for prostate cancer. Proponents of both HDR-BT monotherapy and robotic arm SBRT claim that these modalities are as efficacious as intensity-modulated radiation therapy in treating prostate cancer. Moreover, proponents of robotic arm SBRT believe it is more effective than HDR-BT monotherapy because SBRT is non-invasive, touting it as 'virtual HDR-BT.' We perform a comparative effective analysis of the two technologies. The tumor control rates and toxicities of HDR-BT monotherapy and robotic arm SBRT are promising. However, at present, it would be inappropriate to state that HDR-BT monotherapy and robotic arm SBRT are as efficacious or effective as other treatment modalities for prostate cancer, which have stronger foundations of evidence. Studies reporting on these technologies have relatively short follow-up time, few patients and are largely retrospective. PMID:25540018

  10. Impaired immune regulation after radioiodine therapy for Graves' disease and the protective effect of Methimazole.

    PubMed

    Côté-Bigras, Sarah; Tran, Viet; Turcotte, Sylvie; Rola-Pleszczynski, Marek; Verreault, Jean; Rottembourg, Diane

    2016-06-01

    Both therapies for Graves' disease (GD), radioactive iodine (RAI) and antithyroid drugs (ATD), were reported to have specific immune effects. We aimed at investigating the effects of RAI therapy on cellular subsets involved in immune regulation. We conducted a thirty day follow-up prospective cohort study of adult patients. Patients eligible for RAI therapy at our centre were approached. Twenty seven patients with GD were recruited, among whom 11 were treated with ATD. Twenty-two healthy subjects (HS) were also studied. Over time, frequency of regulatory T cells (Treg) and of invariant natural killer T cells (iNKT), along with Treg cell-mediated suppression and underlying mechanisms, were monitored in the peripheral blood. Variance in frequency of Treg and iNKT after RAI therapy was higher in GD patients than in HS over time (p < 0.0001). Reduced Treg suppressive function was observed after RAI therapy in GD patients (p = 0.002). ATD medication prior to RAI dampened these outcomes: less variation of Treg frequency (p = 0.0394), a trend toward less impaired Treg function, and prevention of reduced levels of suppressive cytokines (p < 0.05). Shortly after RAI therapy, alterations in immunoregulatory cells in patients with GD were observed and partially prevented by an ATD pretreatment. Worsening of autoimmunity after RAI was explained in previous studies by enhanced immune activity. This study adds new highlights on immune regulation deficiencies after therapeutic interventions in thyroid autoimmunity. PMID:26701678

  11. Long-term Survival and Toxicity in Patients Treated With High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

    SciTech Connect

    Spratt, Daniel E.; Pei, Xin; Yamada, Josh; Kollmeier, Marisa A.; Cox, Brett; Zelefsky, Michael J.

    2013-03-01

    Purpose: To report long-term survival and toxicity outcomes with the use of high-dose intensity modulated radiation therapy (IMRT) to 86.4 Gy for patients with localized prostate cancer. Methods and Materials: Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified by prognostic risk group based on National Comprehensive Cancer Network risk classification criteria. A total of 587 patients (59%) were treated with neoadjuvant and concurrent androgen deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range, 1-14 years). Results: For low-, intermediate-, and high-risk groups, 7-year biochemical relapse-free survival outcomes were 98.8%, 85.6%, and 67.9%, respectively (P<.001), and distant metastasis-free survival rates were 99.4%, 94.1%, and 82.0% (P<.001), respectively. On multivariate analysis, T stage (P<.001), Gleason score (P<.001), and >50% of initial biopsy positive core (P=.001) were predictive for distant mestastases. No prostate cancer-related deaths were observed in the low-risk group. The 7-year prostate cancer-specific mortality (PCSM) rates, using competing risk analysis for intermediate- and high-risk groups, were 3.3% and 8.1%, respectively (P=.008). On multivariate analysis, Gleason score (P=.004), percentage of biopsy core positivity (P=.003), and T-stage (P=.033) were predictive for PCSM. Actuarial 7-year grade 2 or higher late gastrointestinal and genitourinary toxicities were 4.4% and 21.1%, respectively. Late grade 3 gastrointestinal and genitourinary toxicity was experienced by 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. Conclusions: This study represents the largest cohort of patients treated with high-dose radiation to 86.4 Gy, using IMRT for localized prostate cancer, with the longest follow-up to date

  12. Paclitaxel and Trastuzumab as Maintenance Therapy in Patients with HER2-Positive Metastatic Breast Cancer Who Underwent High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation.

    PubMed

    Cheng, Yee Chung; Rondón, Gabriela; Anderlini, Paolo; Khouri, Issa F; Champlin, Richard E; Ueno, Naoto T

    2013-01-01

    We examined the feasibility and safety of using paclitaxel and trastuzumab as maintenance therapy after high-dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation (AHST) for patients with HER2-positive metastatic breast cancer. Ten patients (9 women and 1 man) were enrolled in the study. The median age was 46.5 years (range, 27-65 years). The median follow-up time was 1003 days (range, 216-2526 days). All patients had metastatic disease, but 2 had only bone metastasis. One patient had complete response, 6 had partial response and 3 had stable disease to the standard-dose chemotherapy prior to transplantation. The conditioning regimen consisted of cyclophosphamide, carmustine, and thiotepa. After AHST, patients received weekly paclitaxel for 12 doses and trastuzumab every 3 weeks for 1 year as maintenance therapy. All patients experienced successful engraftment. The only grade 4 toxic effects observed were leukopenia and thrombocytopenia. The most common grade 3 toxic effect was neutropenic fever. No treatment-related deaths were observed. The median progression-free survival time was 441 days, and the median overall survival time was 955 days. Two patients died in accidents while their disease remained in remission. Five patients died with disease progression. At the time of this report, 3 patients are alive with stable disease, 1 of whom has remained free of disease progression for 2526 days since transplantation. Our findings indicate that paclitaxel plus trastuzumab as maintenance therapy after HDC with AHST for patients with HER2-positive metastatic breast cancer not only is feasible and safe but also results in survival outcomes similar to historical results. PMID:24155780

  13. Salvage therapy with high-dose chemotherapy and peripheral blood stem cell transplant in patients with primary mediastinal nonseminomatous germ cell tumors.

    PubMed

    Suleiman, Yaman; Siddiqui, Bilal K; Brames, Mary J; Abonour, Rafat; Einhorn, Lawrence H

    2013-01-01

    Salvage therapy with high-dose chemotherapy (HDCT) and bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) has curative potential in patients with recurrent germ cell tumor. However, patients with primary mediastinal nonseminomatous germ cell tumors (PMNSGCTs) have had poor results with any form of salvage chemotherapy including HDCT. We switched from BMT to PBSCT in 1996. One hundred sixteen of 184 patients (63%) with recurrent or refractory germ cell tumors treated from 1996 to 2004 were alive and continuously disease-free. PMNSGCTs were excluded from that study because of poor results in the patient population with HDCT and BMTs. In 2006, we resumed treating patients with recurrent PMNSGCT with 2 consecutive courses of HDCT consisting of carboplatin 700 mg/m(2) × 3 plus etoposide 750 mg/m(2) × 3 and each followed by an infusion of autologous peripheral-blood hematopoietic stem cells with a second course 3 to 4 weeks later. Twelve patients were treated: 11 as initial salvage chemotherapy and 1 as fourth-line therapy. Eight of the 12 patients had major thoracic resections at the time of the relapse after initial chemotherapy. Three of the 12 patients achieved complete remission (CR; 10, 15, and 50 months' duration). One patient remains continuously with no evidence of disease (NED) at 50 months. An additional patient is currently NED at 52 months with HDCT and subsequent surgery. Median survival for the 12 patients was 11 months (range, 4-52 months). Results with tandem transplant for recurrent PMNSGCT remain poor compared to primary testis cancer, but durable CR and probable cure can be achieved in a small subset of patients with PMNSGCT. In our opinion, salvage surgical resection if anatomically feasible is the preferred option for patients with PMNSGT progressing after initial chemotherapy. PMID:22892555

  14. Results of combined photodynamic therapy (PDT) and high dose rate brachytherapy (HDR) in treatment of obstructive endobronchial non-small cell lung cancer

    NASA Astrophysics Data System (ADS)

    Weinberg, Benjamin D.; Allison, Ron R.; Sibata, Claudio; Parent, Teresa; Downie, Gordon

    2009-06-01

    We reviewed the outcome of combined photodynamic therapy (PDT) and high dose rate brachytherapy (HDR) for patients with symptomatic obstruction from endobronchial non-small cell lung cancer. Methods: Nine patients who received combined PDT and HDR for endobronchial cancers were identified and their charts reviewed. The patients were eight males and one female aged 52-73 at diagnosis, initially presenting with various stages of disease: stage IA (N=1), stage IIA (N=1), stage III (N=6), and stage IV (N=1). Intervention was with HDR (500 cGy to 5 mm once weekly for 3 weeks) and PDT (2 mg/kg Photofrin, followed by 200 J/cm2 illumination 48 hours post infusion). Treatment group 1 (TG-1, N=7) received HDR first; Treatment group 2 (TG-2, N=2) received PDT first. Patients were followed by regular bronchoscopies. Results: Treatments were well tolerated, all patients completed therapy, and none were lost to follow-up. In TG-1, local tumor control was achieved in six of seven patients for: 3 months (until death), 15 months, 2+ years (until death), 2+ years (ongoing), and 5+ years (ongoing, N=2). In TG-2, local control was achieved in only one patient, for 84 days. Morbidities included: stenosis and/or other reversible benign local tissue reactions (N=8); photosensitivity reaction (N=2), and self-limited pleural effusion (N=2). Conclusions: Combined HDR/PDT treatment for endobronchial tumors is well tolerated and can achieve prolonged local control with acceptable morbidity when PDT follows HDR and when the spacing between treatments is one month or less. This treatment regimen should be studied in a larger patient population.

  15. Redefining High-Risk Prostate Cancer Based on Distant Metastases and Mortality After High-Dose Radiotherapy With Androgen Deprivation Therapy

    SciTech Connect

    Tendulkar, Rahul D.; Reddy, Chandana A.; Stephans, Kevin L.; Ciezki, Jay P.; Klein, Eric A.; Mahadevan, Arul; Kupelian, Patrick A.

    2012-03-15

    Purpose: Modern outcomes of high-dose external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT) for high-risk (HR) prostate cancer are not well described. Methods and Materials: We identified 585 patients who met HR criteria by 2010 National Comprehensive Cancer Network guidelines, who were treated with EBRT consisting of {>=}74 Gy from 1996 to 2008 at Cleveland Clinic, of whom 95% received ADT. We analyzed biochemical relapse-free survival (bRFS), distant metastases-free survival (DMFS), and prostate cancer-specific mortality (PCSM). Results: The median EBRT dose was 78 Gy, and median ADT duration was 6 months. At 10 years, the bRFS was 50.2%, the DMFS was 71.6%, and the PCSM was 14.4%. On multivariate analysis, significant predictors of bRFS were biopsy Gleason score (bGS) of 8 to 10, stage T3, and prostate-specific antigen (PSA) concentration; predictors of DMFS were bGS of 8 to 10 and stage T3; the only predictor of PCSM was bGS of 8 to 10. The duration of ADT was not predictive of any endpoint. We identified an unfavorable high-risk (UHR) group of stage T1-T2 tumors consisting of bGS of 8 with PSA of >10 ng/ml or bGS of 9 to 10 with any PSA level; the remaining clinically localized cancers comprised the favorable high-risk (FHR) group. Comparing FHR, UHR, and stage T3 groups, the DMFS rates were 81.4%, 57.8%, and 59.1% (p < 0.0001), and the PCSM rates were 7.5%, 28.4%, and 20.6% at 10 years, respectively (p = 0.006). Conclusion: A bGS of 8 to 10 is the strongest predictor of bRFS, DMFS, and PCSM after high-dose EBRT with ADT. The duration of ADT did not correlate with outcome. Future studies should account for the heterogeneity in HR prostate cancer.

  16. Comparison of High-Dose Corticosteroid Pulse Therapy and Combination Therapy Using Oral Cyclosporine with Low-Dose Corticosteroid in Severe Alopecia Areata

    PubMed Central

    Yeo, In Kwon; Ko, Eun Jung; No, Yeon A; Lim, Ee Seok; Park, Kui Young; Li, Kapsok; Kim, Beom Joon; Seo, Seong Jun; Kim, Myeung Nam

    2015-01-01

    Background Severe alopecia areata (AA) is resistant to conventional treatment. Although systemic oral corticosteroids are an effective treatment for patients with severe AA, those drugs have many adverse effects. Corticosteroid pulse therapy has been introduced to increase therapeutic effects and reduce adverse effects. However, the treatment modality in severe AA is still controversial. Objective To evaluate the effectiveness of corticosteroid pulse therapy in patients with severe AA compared with treatment with oral cyclosporine with corticosteroid. Methods A total of 82 patients with severe AA were treated with corticosteroid pulse therapy, and 60 patients were treated with oral cyclosporine with corticosteroid. Both groups were retrospectively evaluated for therapeutic efficacy according to AA type and disease duration. Results In 82 patients treated with corticosteroid pulse therapy, 53 (64.6%) were good responders (>50% hair regrowth). Patients with the plurifocal (PF) type of AA and those with a short disease duration (≤3 months) showed better responses. In 60 patients treated with oral cyclosporine with corticosteroid, 30 (50.0%) patients showed a good response. The AA type or disease duration, however, did not significantly affect the response to treatment. Conclusion Corticosteroid pulse therapy may be a better treatment option than combination therapy in severe AA patients with the PF type. PMID:26719635

  17. Iodine kinetics and dosimetry in the salivary glands during repeated courses of radioiodine therapy for thyroid cancer

    SciTech Connect

    Liu, B.; Huang, R.; Kuang, A.; Zhao, Z.; Zeng, Y.; Wang, J.; Tian, R.

    2011-10-15

    Purpose: The present study was conducted to investigate salivary iodine kinetics and dosimetry during repeated courses of radioiodine ({sup 131}I) therapy for differentiated thyroid cancer (DTC). Such data could provide a better understanding of the mechanisms of {sup 131}I induced salivary toxicity and help to develop appropriate methods to reduce this injury. Methods: Seventy-eight consecutive DTC patients (mean age 45 {+-} 17 years, 60%, female) undergoing {sup 131}I therapy for remnant ablation or metastatic tumors were prospectively recruited. Planar quantitative scintigraphy of head-neck images was serially acquired after administration of 2.9-7.4 GBq of {sup 131}I to assess kinetics in the salivary glands of patients. Salivary absorbed doses were calculated based on the schema of Medical Internal Radiation Dosimetry. Results: The maximum uptakes in percentage of administered {sup 131}I activity per kilogram of gland tissue (%/kg) were 12.9% {+-} 6.5%/kg (range, 0.4%-37.3%/kg) and 12.3% {+-} 6.2%/kg (range, 0.4%-35.1%/kg) for the parotid and submandibular glands, respectively. Statistically significant correlations of maximum uptake versus cumulative activity (r = -0.74, P < 0.01, for the parotid glands; r = -0.71, P < 0.01, for the submandibular glands) and treatment cycle (P < 0.001, for both gland types) were found. The effective half-lives of {sup 131}I in the parotid and submandibular glands were 9.3 {+-} 3.5 h (range, 1.5-19.8 h) and 8.6 {+-} 3.2 h (range, 0.8-18.0 h), respectively. A statistically significant correlation was observed between effective half-life with cumulative activity (r = 0.37, P < 0.01) and treatment cycle (P = 0.03) only for the parotid glands. The calculated absorbed doses were 0.20 {+-} 0.10 mGy/MBq (range, 0.01-0.92 mGy/MBq) and 0.25 {+-} 0.09 mGy/MBq (range, 0.01-1.52 mGy/MBq) for the parotid and submandibular glands, respectively. The photon contribution to the salivary absorbed dose was minimal in relation to the beta dose

  18. Rituximab-CHOP-ESHAP vs CHOP-ESHAP-high-dose therapy vs conventional CHOP chemotherapy in high-intermediate and high-risk aggressive non-Hodgkin's lymphoma.

    PubMed

    Intragumtornchai, Tanin; Bunworasate, Udomsak; Nakorn, Thanyaphong Na; Rojnuckarin, Ponlapat

    2006-07-01

    With currently available combination chemotherapy regimens, the outcome of the patients newly diagnosed with aggressive non-Hodgkin's lymphoma (NHL) identified as 'high' and 'high-intermediate' risk groups according to the international prognostic index (IPI) is still unsatisfactory and a more innovative therapy is urgently required to improve the survival of the patients. The purpose of this study was to compare the efficacy of rituximab given in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and ESHAP (etoposide, methylprednisolone, high-dose Ara-C, cisplatin) vs CHOP-ESHAP and upfront high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) vs standard CHOP in patients aged < or = 65 years old newly diagnosed with 'high' and 'high-intermediate' risk aggressive lymphoma enrolled onto two consecutive treatment trials at the institute. Between May 1995 - July 2002, 84 patients, aged 15 - 65 years old, with newly diagnosed aggressive NHL and an age-adjusted IPI of 2 or 3 were enrolled. The median age of the patients was 38 years (range 15 - 65). The baseline demographic features, in particular the major prognostic variables, were similar between the treatment groups. Patients treated with rituximab-CHOP-ESHAP received eight cycles of rituximab (375 mg m(-2) on day 1 of cycles 1 - 6 and days 21 and 28 of cycle 7) plus CHOP (day 3 of cycles 1, 3 and 5) and ESHAP (day 3 of cycles 2, 4 and 6 and day 1 of cycle 7) at 21-day intervals. Patients enrolled onto the CHOP-ESHAP-HDT arm (n = 23) were treated with three courses of CHOP and then switched to two or four cycles of ESHAP followed by HDT. Patients treated with CHOP alone (n = 25) were treated with the standard eight cycles of CHOP. The rate of complete remission was significantly improved with rituximab-CHOP-ESHAP compared with either CHOP-ESHAP-HDT or CHOP alone (67% compared with 44% and 36%, respectively; p = 0.043). With a median follow-up time of 53 months, the 5

  19. Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiation Therapy in the Treatment of Intermediate-Risk Prostate Cancer - Long Term Results

    SciTech Connect

    Cury, Fabio L.; Duclos, Marie; Aprikian, Armen; Patrocinio, Horacio; Kassouf, Wassim; Shenouda, George; Faria, Sergio; David, Marc; Souhami, Luis

    2012-03-15

    Purpose: We present the long-term results of a cohort of patients with intermediate-risk prostate cancer (PC) treated with single-fraction high-dose-rate brachytherapy (HDRB) combined with hypofractionated external beam radiation therapy (HypoRT). Methods and Materials: Patients were treated exclusively with HDRB and HypoRT. HDRB delivered a dose of 10 Gy to the prostate surface and HypoRT consisted of 50 Gy delivered in 20 daily fractions. The first 121 consecutive patients with a minimum of 2 years posttreatment follow-up were assessed for toxicity and disease control. Results: The median follow-up was 65.2 months. No acute Grade III or higher toxicity was seen. Late Grade II gastrointestinal toxicity was seen in 9 patients (7.4%) and Grade III in 2 (1.6%). Late Grade III genitourinary toxicity was seen in 2 patients (1.6%). After a 24-month follow-up, a rebiopsy was offered to the first 58 consecutively treated patients, and 44 patients agreed with the procedure. Negative biopsies were found in 40 patients (91%). The 5-year biochemical relapse-free survival rate was 90.7% (95% CI, 84.5-96.9%), with 13 patients presenting biochemical failure. Among them, 9 were diagnosed with distant metastasis. Prostate cancer-specific and overall survival rates at 5 years were 100% and 98.8% (95% CI, 96.4-100%), respectively. Conclusion: The combination of HDRB and HypoRT is well tolerated, with acceptable toxicity rates. Furthermore, results from rebiopsies revealed an encouraging rate of local control. These results confirm that the use of conformal RT techniques, adapted to specific biological tumor characteristics, have the potential to improve the therapeutic ratio in intermediate-risk PC patients.

  20. An oral high dose of cholecalciferol restores vitamin D status in deficient postmenopausal HIV-1-infected women independently of protease inhibitors therapy: a pilot study.

    PubMed

    Pepe, Jessica; Mezzaroma, Ivano; Fantauzzi, Alessandra; Falciano, Mario; Salotti, Alessandra; Di Traglia, Mario; Diacinti, Daniele; Biondi, Piergianni; Cipriani, Cristiana; Cilli, Mirella; Minisola, Salvatore

    2016-07-01

    The best repletion and maintenance dosing regimens with cholecalciferol in vitamin D-deficient HIV-1 patients remain unknown. Protease inhibitors (PIs) have been shown to inhibit vitamin D 1α- and 25α-hydroxylation in hepatocyte and monocyte cultures. We therefore evaluated the effect of a single high dose of cholecalciferol in vitamin D-deficient HIV-1 postmenopausal women undergoing treatment with highly active anti-retroviral therapy (cART), with and without PIs. Forty HIV-1 postmenopausal women treated with cART, with hypovitaminosis D (<20 ng/ml), were enrolled. We measured serum changes of 25-hydroxyvitamin D [25(OH)D]; 1,25-dihydroxyvitamin D [1,25(OH)2D], parathyroid hormone (PTH), serum calcium, and urinary calcium excretion following a loading dose of 600,000 IU of cholecalciferol after 3, 30, 60, 90, and 120 days. Patients were divided into two groups, whether or not they were taking PI. A significant increase in mean 25(OH)D and 1,25(OH)2D levels at day 3 and throughout the entire observation period was found in both groups (p < 0.001). PTH levels concomitantly decreased in both groups (p < 0.001). Mean albumin-adjusted serum calcium increases with respect to baseline were significant only at day 3 and day 30 for both groups (p < 0.01). Considering remaining parameters, there were no significant differences between the groups at any time, by two-way RM ANOVA. An oral dose of 600,000 IU of cholecalciferol in HIV-1 postmenopausal women rapidly increases 25(OH)D and 1,25(OH)2D levels reducing PTH levels, regardless of the presence of PIs in the cART scheme. PMID:26254790

  1. High-Dose Terazosin Therapy (5 mg) in Korean Patients with Lower Urinary Tract Symptoms with or without Concomitant Hypertension: A Prospective, Open-Label Study

    PubMed Central

    Kwak, Cheol; Lee, Jeong Ki

    2007-01-01

    Purpose We determined the efficacy and safety of a relatively high dose of terazosin (5 mg) in Korean patients with lower urinary tract symptoms (LUTS), with or without concomitant hypertension. Materials and Methods From July to December 2006, 200 men who consecutively presented with LUTS were prospectively studied. Eight weeks after treatment, blood pressure (BP), uroflowmetry, and International Prostate Symptom Score (I-PSS) were assessed. For analysis purposes, patients were stratified according to concomitant hypertension. Of the 200 patients, 173 completed the scheduled eight-week treatment period. Results At baseline, no differences were evident in the two groups in terms of I-PSS, Qmax, PVR and BP. After eight weeks of treatment-although I-PSS and uroflowmetry parameters were not significantly different in the two groups-systolic and diastolic BP in the non-hypertensive control group were higher than in the hypertensive group (p= 0.001 and p = 0.0100, respectively). Changes in I-PSS, uroflowmetry parameters, and BPs measured at week eight post-treatment commencement did not significantly differ between the two groups. Moreover, the addition of 5 mg of terazosin to antihypertensives did not cause a significant reduction in either systolic or diastolic BP in either group. Conclusion Adding terazosin to existing antihypertensive regimens did not seem to increase the incidence of adverse events. Our findings suggest that 5 mg terazosin is effective and that it has an acceptable safety profile as an add-on therapy for patients with LUTS and concomitant hypertension. PMID:18159592

  2. High-Dose and Extended-Field Intensity Modulated Radiation Therapy for Early-Stage NK/T-Cell Lymphoma of Waldeyer's Ring: Dosimetric Analysis and Clinical Outcome

    SciTech Connect

    Bi, Xi-Wen; Li, Ye-Xiong Fang, Hui; Jin, Jing; Wang, Wei-Hu; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Ren, Hua; Dai, Jian-Rong

    2013-12-01

    Purpose: To assess the dosimetric benefit, treatment outcome, and toxicity of high-dose and extended-field intensity modulated radiation therapy (IMRT) in patients with early-stage NK/T-cell lymphoma of Waldeyer's ring (WR-NKTCL). Methods and Materials: Thirty patients with early-stage WR-NKTCL who received extended-field IMRT were retrospectively reviewed. The prescribed dose was 50 Gy to the primary involved regions and positive cervical lymph nodes (planning target volume requiring radical irradiation [PTV{sub 50}]) and 40 Gy to the negative cervical nodes (PTV{sub 40}). Dosimetric parameters for the target volume and critical normal structures were evaluated. Locoregional control (LRC), overall survival (OS), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Results: The median mean doses to the PTV{sub 50} and PTV{sub 40} were 53.2 Gy and 43.0 Gy, respectively. Only 1.4% of the PTV{sub 50} and 0.9% of the PTV{sub 40} received less than 95% of the prescribed dose, indicating excellent target coverage. The average mean doses to the left and right parotid glands were 27.7 and 28.4 Gy, respectively. The 2-year OS, PFS, and LRC rates were 71.2%, 57.4%, and 87.8%. Most acute toxicities were grade 1 to 2, except for grade ≥3 dysphagia and mucositis. The most common late toxicity was grade 1-2 xerostomia, and no patient developed any ≥grade 3 late toxicities. A correlation between the mean dose to the parotid glands and the degree of late xerostomia was observed. Conclusions: IMRT achieves excellent target coverage and dose conformity, as well as favorable survival and locoregional control rates with acceptable toxicities in patients with WR-NKTCL.

  3. Modified total body irradiation as a planned second high-dose therapy with stem cell infusion for patients with bone-based malignancies

    SciTech Connect

    Zaucha, Renata E.; Buckner, Dean C.; Barnett, Todd; Holmberg, Leona A.; Gooley, Ted; Hooper, Heather A. P.A.-C.; Maloney, David G.; Appelbaum, Frederick; Bensinger, William I. . E-mail: wbensing@fhcrc.org

    2006-01-01

    Purpose: To estimate the maximum tolerated dose of hyperfractionated total marrow irradiation (TMI) as a second consolidation after high-dose chemotherapy with autologous or syngeneic blood stem cell transfusion for patients with bone/bone marrow-based malignant disease. Patients and Methods: Fifty-seven patients aged 3-65 years (median, 45 years), including 21 with multiple myeloma, 24 with breast cancer, 10 with sarcoma, and 2 with lymphoma, were treated with 1.5 Gy administered twice daily to a total dose of 12 Gy (n = 27), 13.5 Gy (n = 12), and 15 Gy (n = 18). Median time between the 2 transplants was 105 days (range, 63-162 days). Results: All patients engrafted neutrophils (median, Day 11; range, Day 9-23) and became platelet independent (median, Day 9; range, Day 7-36). There were 5 cases of Grade 3-4 regimen-related pulmonary toxicity, 1 at 12 Gy, and 4 at 15 Gy. Complete responses, partial responses, and stabilizations were achieved in 33%, 26%, and 41% of patients, respectively. Kaplan-Meier estimates of 5-year progression-free survival and overall survival for 56 evaluable patients are 24% and 36%, respectively. Median time of follow-up among survivors was 96 months (range, 77-136 months). Conclusion: Total marrow irradiation as a second myeloablative therapy is feasible. The estimated maximum tolerated dose for TMI in a tandem transplant setting was 13.5 Gy. Because 20% of patients are surviving at 8 years free of disease, further studies of TMI are warranted.

  4. Dosimetric and radiobiological comparison of volumetric modulated arc therapy, high-dose rate brachytherapy, and low-dose rate permanent seeds implant for localized prostate cancer.

    PubMed

    Yang, Ruijie; Zhao, Nan; Liao, Anyan; Wang, Hao; Qu, Ang

    2016-01-01

    To investigate the dosimetric and radiobiological differences among volumetric modulated arc therapy (VMAT), high-dose rate (HDR) brachytherapy, and low-dose rate (LDR) permanent seeds implant for localized prostate cancer. A total of 10 patients with localized prostate cancer were selected for this study. VMAT, HDR brachytherapy, and LDR permanent seeds implant plans were created for each patient. For VMAT, planning target volume (PTV) was defined as the clinical target volume plus a margin of 5mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78Gy in 39 fractions were prescribed for PTV. For HDR and LDR plans, the dose prescription was D90 of 34Gy in 8.5Gy per fraction, and 145Gy to clinical target volume, respectively. The dose and dose volume parameters were evaluated for target, organs at risk, and normal tissue. Physical dose was converted to dose based on 2-Gy fractions (equivalent dose in 2Gy per fraction, EQD2) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The Dmean (EQD2) of rectum decreased 22.36Gy in HDR and 17.01Gy in LDR from 30.24Gy in VMAT, respectively. The Dmean (EQD2) of bladder decreased 6.91Gy in HDR and 2.53Gy in LDR from 13.46Gy in VMAT. For the femoral heads and normal tissue, the mean doses were also significantly reduced in both HDR and LDR compared with VMAT. For the urethra, the mean dose (EQD2) was 80.26, 70.23, and 104.91Gy in VMAT, HDR, and LDR brachytherapy, respectively. For localized prostate cancer, both HDR and LDR brachytherapy were clearly superior in the sparing of rectum, bladder, femoral heads, and normal tissue compared with VMAT. HDR provided the advantage in sparing of urethra compared with VMAT and LDR. PMID:27400663

  5. High Doses of Daunorubicin during Induction Therapy of Newly Diagnosed Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis of Prospective Clinical Trials

    PubMed Central

    Gong, Qiang; Zhou, Lixin; Xu, Shuangnian; Li, Xi; Zou, Yunding; Chen, Jieping

    2015-01-01

    The right dose of daunorubicin (DNR) for the treatment of newly diagnosed acute myeloid leukemia (AML) is uncertain. Previous trials have shown conflicting results concerning the efficacy of high or low doses of daunorubicin to induction chemotherapy for newly diagnosed AML. A systematic review and meta-analysis was conducted to resolve this controversial issue. We compared the efficacy and safety of high doses of daunorubicin (HD-DNR) and traditional low doses of daunorubicin (LD-DNR) or idarubicin (IDA) during induction therapy of newly diagnosed AML. Data of 3,824 patients from 1,796 articles in the literature were retrieved and six randomized controlled trials were analyzed. The primary outcomes were overall survival (OS), disease-free survival (DFS), and event-free survival (EFS). The secondary outcomes included complete remission (CR), relapse, and toxicity. The meta-analysis results suggest that comparing HD-DNR with LD-DNR, there were significant differences in CR (RR = 1.19, 95%CI[1.12,1.18], p<0.00001), OS(HR = 0.88, 95%CI[0.79,0.99], p = 0.002), and EFS (HR = 0.86, 95%CI [0.74, 1.00], p = 0.008), but not in DFS, relapse, and toxicity. There were no statistically significant differences in any other outcomes between HD-DNR and IDA. The analysis indicates that compared with LD-DNR, HD-DNR can significantly improve CR, OS and EFS but not DFS, and did not increase occurrence of relapse and toxicity. PMID:25993000

  6. Comparison of radioiodine with radioiodine plus lithium in the treatment of Graves' hyperthyroidism.

    PubMed

    Bogazzi, F; Bartalena, L; Brogioni, S; Scarcello, G; Burelli, A; Campomori, A; Manetti, L; Rossi, G; Pinchera, A; Martino, E

    1999-02-01

    Effectiveness of radioiodine for Graves' hyperthyroidism depends also on its intrathyroidal persistence. The latter is enhanced by lithium by blocking iodine release from the thyroid. One hundred ten patients with Graves' hyperthyroidism were randomly assigned to treatment with radioiodine or radioiodine plus lithium, stratified according to goiter size (< or =40 or >40 mL) and evaluated for changes in thyroid function and goiter size, at monthly intervals, for 12 months. Cure of hyperthyroidism occurred in 33 of 46 patients (72%) treated with radioiodine and in 45 of 54 patients (83%) treated with radioiodine plus lithium. The probability of curing hyperthyroidism was higher and its control prompter (P = 0.02) in the radioiodine-plus-lithium group. Patients with < or =40-mL goiters had similar persistence of hyperthyroidism (13%), but lithium-treated patients had hyperthyroidism controlled earlier (P = 0.04). Among patients with >40-mL goiters, hyperthyroidism was cured in 6 of 15 patients (40%) treated with radioiodine alone and in 12 of 16 patients (75%) treated with radioiodine plus lithium (P = 0.07), and cure occurred earlier in the latter (P = 0.05). Goiters shrank in both groups (P < 0.0001), more effectively and promptly (P < 0.0005) in the radioiodine-plus-lithium group. Serum free T4 and T3 levels increased shortly after therapy only in the radioiodine group (P < 0.01). Lithium carbonate enhances the effectiveness of radioiodine therapy, in terms of prompter control of hyperthyroidism, in patients with small or large goiters. In the latter group, lithium also increases the rate of permanent control of hyperthyroidism. PMID:10022407

  7. Impact of Dose to the Bladder Trigone on Long-Term Urinary Function After High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

    SciTech Connect

    Ghadjar, Pirus; Zelefsky, Michael J.; Spratt, Daniel E.; Munck af Rosenschöld, Per; Oh, Jung Hun; Hunt, Margie; Kollmeier, Marisa; Happersett, Laura; Yorke, Ellen; Deasy, Joseph O.; Jackson, Andrew

    2014-02-01

    Purpose: To determine the potential association between genitourinary (GU) toxicity and planning dose–volume parameters for GU pelvic structures after high-dose intensity modulated radiation therapy in localized prostate cancer patients. Methods and Materials: A total of 268 patients who underwent intensity modulated radiation therapy to a prescribed dose of 86.4 Gy in 48 fractions during June 2004-December 2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose–volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analyses were done by the Kaplan-Meier method and Cox proportional hazard models, respectively. Results: Median follow-up was 5 years (range, 3-7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=.006), the V90 of the trigone (P=.006), and the maximal dose to the trigone (P=.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=.009) and increased maximal dose to the trigone (P=.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high risk, and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk patients (29%) and 5 of 68 low-risk patients (7%) experienced an IPSS sum increase ≥10 (P=.001; odds ratio 5.19). Conclusions: The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the

  8. Radioactive Iodine (Radioiodine) Therapy

    MedlinePlus

    ... low thyroid hormone levels (a condition known as hypothyroidism ), which in turn causes the pituitary gland to release more TSH. This intentional hypothyroidism is temporary, but it often causes symptoms like ...

  9. High-Dose Radiotherapy With or Without Androgen Deprivation Therapy for Intermediate-Risk Prostate Cancer: Cancer Control and Toxicity Outcomes

    SciTech Connect

    Edelman, Scott; Liauw, Stanley L.; Rossi, Peter J.; Cooper, Sherrie; Jani, Ashesh B.

    2012-08-01

    Purpose: To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). Methods and Materials: Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as {>=}T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: {>=}T3, prostate-specific antigen level >20 ng/mL, GS {>=}8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADT and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. Results: For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% (p = 0.138) and the 5-year OS rate was 87% vs. 80% (p = 0.159). On multivariate analysis, percent positive cores (PPC) (p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% (p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. Conclusions: Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy

  10. Phase II Study of Accelerated High-Dose Radiotherapy With Concurrent Chemotherapy for Patients With Limited Small-Cell Lung Cancer: Radiation Therapy Oncology Group Protocol 0239

    SciTech Connect

    Komaki, Ritsuko; Paulus, Rebecca; Ettinger, David S.; Videtic, Gregory M.M.; Bradley, Jeffrey D.; Glisson, Bonnie S.; Sause, William T.; Curran, Walter J.; Choy, Hak

    2012-07-15

    Purpose: To investigate whether high-dose thoracic radiation given twice daily during cisplatin-etoposide chemotherapy for limited small-cell lung cancer (LSCLC) improves survival, acute esophagitis, and local control rates relative to findings from Intergroup trial 0096 (47%, 27%, and 64%). Patients and Methods: Patients were accrued over a 3-year period from 22 US and Canadian institutions. Patients with LSCLC and good performance status were given thoracic radiation to 61.2 Gy over 5 weeks (daily 1.8-Gy fractions on days 1-22, then twice-daily 1.8-Gy fractions on days 23-33). Cisplatin (60 mg/m{sup 2} IV) was given on day 1 and etoposide (120 mg/m{sup 2} IV) on days 1-3 and days 22-24, followed by 2 cycles of cisplatin plus etoposide alone. Patients who achieved complete response were offered prophylactic cranial irradiation. Endpoints included overall and progression-free survival; severe esophagitis (Common Toxicity Criteria v 2.0) and treatment-related fatalities; response (Response Evaluation Criteria in Solid Tumors); and local control. Results: Seventy-two patients were accrued from June 2003 through May 2006; 71 were evaluable (median age 63 years; 52% female; 58% Zubrod 0). Median survival time was 19 months; at 2 years, the overall survival rate was 36.6% (95% confidence interval [CI] 25.6%-47.7%), and progression-free survival 19.7% (95% CI 11.4%-29.6%). Thirteen patients (18%) experienced severe acute esophagitis, and 2 (3%) died of treatment-related causes; 41% achieved complete response, 39% partial response, 10% stable disease, and 6% progressive disease. The local control rate was 73%. Forty-three patients (61%) received prophylactic cranial irradiation. Conclusions: The overall survival rate did not reach the projected goal; however, rates of esophagitis were lower, and local control higher, than projected. This treatment strategy is now one of three arms of a prospective trial of chemoradiation for LSCLC (Radiation Therapy Oncology Group 0538

  11. Preliminary Toxicity Analysis of 3-Dimensional Conformal Radiation Therapy Versus Intensity Modulated Radiation Therapy on the High-Dose Arm of the Radiation Therapy Oncology Group 0126 Prostate Cancer Trial

    SciTech Connect

    Michalski, Jeff M.; Yan, Yan; Watkins-Bruner, Deborah; Bosch, Walter R.; Winter, Kathryn; Galvin, James M.; Bahary, Jean-Paul; Morton, Gerard C.; Parliament, Matthew B.; Sandler, Howard M.

    2013-12-01

    Purpose: To give a preliminary report of clinical and treatment factors associated with toxicity in men receiving high-dose radiation therapy (RT) on a phase 3 dose-escalation trial. Methods and Materials: The trial was initiated with 3-dimensional conformal RT (3D-CRT) and amended after 1 year to allow intensity modulated RT (IMRT). Patients treated with 3D-CRT received 55.8 Gy to a planning target volume that included the prostate and seminal vesicles, then 23.4 Gy to prostate only. The IMRT patients were treated to the prostate and proximal seminal vesicles to 79.2 Gy. Common Toxicity Criteria, version 2.0, and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late morbidity scores were used for acute and late effects. Results: Of 763 patients randomized to the 79.2-Gy arm of Radiation Therapy Oncology Group 0126 protocol, 748 were eligible and evaluable: 491 and 257 were treated with 3D-CRT and IMRT, respectively. For both bladder and rectum, the volumes receiving 65, 70, and 75 Gy were significantly lower with IMRT (all P<.0001). For grade (G) 2+ acute gastrointestinal/genitourinary (GI/GU) toxicity, both univariate and multivariate analyses showed a statistically significant decrease in G2+ acute collective GI/GU toxicity for IMRT. There were no significant differences with 3D-CRT or IMRT for acute or late G2+ or 3+ GU toxicities. Univariate analysis showed a statistically significant decrease in late G2+ GI toxicity for IMRT (P=.039). On multivariate analysis, IMRT showed a 26% reduction in G2+ late GI toxicity (P=.099). Acute G2+ toxicity was associated with late G3+ toxicity (P=.005). With dose–volume histogram data in the multivariate analysis, RT modality was not significant, whereas white race (P=.001) and rectal V70 ≥15% were associated with G2+ rectal toxicity (P=.034). Conclusions: Intensity modulated RT is associated with a significant reduction in acute G2+ GI/GU toxicity. There is a trend for a

  12. Investigation of the level of safety for out-patients treated with high dose of 131I in Sudan

    NASA Astrophysics Data System (ADS)

    Saeed, M. K.

    2014-10-01

    The aim of this study was to describe and analyze the patterns of radiation exposure of contacts of Sudanese patients treated with radioactive 131I on an out-patient basis and post discharge after high dose 131I therapy, and also to compare the family members' results with dose constraints proposed by the European Commission (EC). Thermoluminiscent dosimeters (Model TLD-100 H) were used to estimate the effective doses for 40 family members of fifteen patients treated with 131I. The family members wore a TLD in front of the chest for 10 days. The effective dose ranged from 0.23 to 6.74 mSv (mean 1.75 mSv). These findings may be considered when establishing new national guidelines concerning radiation protection and release of patients after a treatment with radioiodine therapy.

  13. The costs of peripheral blood progenitor cell reinfusion mobilised by granulocyte colony-stimulating factor following high dose melphalan as compared with conventional therapy in multiple myeloma.

    PubMed

    Uyl-de Groot, C A; Ossenkoppele, G J; van Riet, A A; Rutten, F F

    1994-01-01

    In a retrospective study, we calculated the treatment costs of 26 patients, who received either high dose melphalan combined with granulocyte colony-stimulating factor (G-CSF; filgrastim)(n = 7) or without G-CSF (n = 11) or alternatively, peripheral blood progenitor cell reinfusion (PBPC) mobilised by G-CSF following high dose melphalan. In comparison with the control group, a shortening of the pancytopenic period and platelet recovery was noticed in the PBPC group. This resulted in a reduction in hospital costs, diagnostics, laboratory services, total parenteral nutrition and transfusions. The average costs per treatment in the PBPC group amounted to about US$ 17,908 as compared to US$ 32,223 in the control group, implying a cost reduction of 44% when changing to PBPC reinfusion. PMID:7517149

  14. Salvage therapy with high-dose cytarabine and mitoxantrone in combination with all-trans retinoic acid and gemtuzumab ozogamicin in acute myeloid leukemia refractory to first induction therapy.

    PubMed

    Hütter-Krönke, Marie-Luise; Benner, Axel; Döhner, Konstanze; Krauter, Jürgen; Weber, Daniela; Moessner, Margit; Köhne, Claus-Henning; Horst, Heinz A; Schmidt-Wolf, Ingo G H; Rummel, Mathias; Götze, Katharina; Koller, Elisabeth; Petzer, Andreas L; Salwender, Hans; Fiedler, Walter; Kirchen, Heinz; Haase, Detlef; Kremers, Stephan; Theobald, Matthias; Matzdorff, Axel C; Ganser, Arnold; Döhner, Hartmut; Schlenk, Richard F

    2016-07-01

    Outcome of patients with primary refractory acute myeloid leukemia remains unsatisfactory. We conducted a prospective phase II clinical trial with gemtuzumab ozogamicin (3 mg/m(2) intravenously on day 1), all-trans retinoic acid (45 mg/m(2) orally on days 4-6 and 15 mg/m(2) orally on days 7-28), high-dose cytarabine (3 g/m(2)/12 h intravenously on days 1-3) and mitoxantrone (12 mg/m(2) intravenously on days 2-3) in 93 patients aged 18-60 years refractory to one cycle of induction therapy. Primary end point of the study was response to therapy; secondary end points included evaluation of toxicities, in particular, rate of sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation. Complete remission or complete remission with incomplete blood count recovery was achieved in 47 (51%) and partial remission in 10 (11%) patients resulting in an overall response rate of 61.5%; 33 (35.5%) patients had refractory disease and 3 patients (3%) died. Allogeneic hematopoietic cell transplantation was performed in 71 (76%) patients; 6 of the 71 (8.5%) patients developed moderate or severe sinusoidal obstruction syndrome after transplantation. Four-year overall survival rate was 32% (95% confidence interval 24%-43%). Patients responding to salvage therapy and undergoing allogeneic hematopoietic cell transplantation (n=51) had a 4-year survival rate of 49% (95% confidence intervaI 37%-64%). Patients with fms-like tyrosine kinase internal tandem duplication positive acute myeloid leukemia had a poor outcome despite transplantation. In conclusion, the described regimen is an effective and tolerable salvage therapy for patients who are primary refractory to one cycle of conventional intensive induction therapy. (clinicaltrials.gov identifier: 00143975). PMID:27036160

  15. Salvage therapy with high-dose cytarabine and mitoxantrone in combination with all-trans retinoic acid and gemtuzumab ozogamicin in acute myeloid leukemia refractory to first induction therapy

    PubMed Central

    Hütter-Krönke, Marie-Luise; Benner, Axel; Döhner, Konstanze; Krauter, Jürgen; Weber, Daniela; Moessner, Margit; Köhne, Claus-Henning; Horst, Heinz A.; Schmidt-Wolf, Ingo G.H.; Rummel, Mathias; Götze, Katharina; Koller, Elisabeth; Petzer, Andreas L.; Salwender, Hans; Fiedler, Walter; Kirchen, Heinz; Haase, Detlef; Kremers, Stephan; Theobald, Matthias; Matzdorff, Axel C.; Ganser, Arnold; Döhner, Hartmut; Schlenk, Richard F.

    2016-01-01

    Outcome of patients with primary refractory acute myeloid leukemia remains unsatisfactory. We conducted a prospective phase II clinical trial with gemtuzumab ozogamicin (3 mg/m2 intravenously on day 1), all-trans retinoic acid (45 mg/m2 orally on days 4–6 and 15 mg/m2 orally on days 7–28), high-dose cytarabine (3 g/m2/12 h intravenously on days 1–3) and mitoxantrone (12 mg/m2 intravenously on days 2–3) in 93 patients aged 18–60 years refractory to one cycle of induction therapy. Primary end point of the study was response to therapy; secondary end points included evaluation of toxicities, in particular, rate of sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation. Complete remission or complete remission with incomplete blood count recovery was achieved in 47 (51%) and partial remission in 10 (11%) patients resulting in an overall response rate of 61.5%; 33 (35.5%) patients had refractory disease and 3 patients (3%) died. Allogeneic hematopoietic cell transplantation was performed in 71 (76%) patients; 6 of the 71 (8.5%) patients developed moderate or severe sinusoidal obstruction syndrome after transplantation. Four-year overall survival rate was 32% (95% confidence interval 24%-43%). Patients responding to salvage therapy and undergoing allogeneic hematopoietic cell transplantation (n=51) had a 4-year survival rate of 49% (95% confidence intervaI 37%-64%). Patients with fms-like tyrosine kinase internal tandem duplication positive acute myeloid leukemia had a poor outcome despite transplantation. In conclusion, the described regimen is an effective and tolerable salvage therapy for patients who are primary refractory to one cycle of conventional intensive induction therapy. (clinicaltrials.gov identifier: 00143975) PMID:27036160

  16. {sup 18}F-Choline Positron Emission Tomography/Computed Tomography–Driven High-Dose Salvage Radiation Therapy in Patients With Biochemical Progression After Radical Prostatectomy: Feasibility Study in 60 Patients

    SciTech Connect

    D'Angelillo, Rolando M.; Sciuto, Rosa; Ramella, Sara; Papalia, Rocco; Jereczek-Fossa, Barbara A.; Trodella, Luca E.; Fiore, Michele; Gallucci, Michele; Maini, Carlo L.; Trodella, Lucio

    2014-10-01

    Purpose: To retrospectively review data of a cohort of patients with biochemical progression after radical prostatectomy, treated according to a uniform institutional treatment policy, to evaluate toxicity and feasibility of high-dose salvage radiation therapy (80 Gy). Methods and Materials: Data on 60 patients with biochemical progression after radical prostatectomy between January 2009 and September 2011 were reviewed. The median value of prostate-specific antigen before radiation therapy was 0.9 ng/mL. All patients at time of diagnosis of biochemical recurrence underwent dynamic {sup 18}F-choline positron emission tomography/computed tomography (PET/CT), which revealed in all cases a local recurrence. High-dose salvage radiation therapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT-positive area. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events, version 3.0, scale. Results: Treatment was generally well tolerated: 54 patients (90%) completed salvage radiation therapy without any interruption. Gastrointestinal grade ≥2 acute toxicity was recorded in 6 patients (10%), whereas no patient experienced a grade ≥2 genitourinary toxicity. No grade 4 acute toxicity events were recorded. Only 1 patient (1.7%) experienced a grade 2 gastrointestinal late toxicity. With a mean follow-up of 31.2 months, 46 of 60 patients (76.6%) were free of recurrence. The 3-year biochemical progression-free survival rate was 72.5%. Conclusions: At early follow-up, {sup 18}F-choline PET/CT-driven high-dose salvage radiation therapy seems to be feasible and well tolerated, with a low rate of toxicity.

  17. Dosimetric Considerations to Determine the Optimal Technique for Localized Prostate Cancer Among External Photon, Proton, or Carbon-Ion Therapy and High-Dose-Rate or Low-Dose-Rate Brachytherapy

    SciTech Connect

    Georg, Dietmar

    2014-03-01

    Purpose: To assess the dosimetric differences among volumetric modulated arc therapy (VMAT), scanned proton therapy (intensity-modulated proton therapy, IMPT), scanned carbon-ion therapy (intensity-modulated carbon-ion therapy, IMIT), and low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy (BT) treatment of localized prostate cancer. Methods and Materials: Ten patients were considered for this planning study. For external beam radiation therapy (EBRT), planning target volume was created by adding a margin of 5 mm (lateral/anterior–posterior) and 8 mm (superior–inferior) to the clinical target volume. Bladder wall (BW), rectal wall (RW), femoral heads, urethra, and pelvic tissue were considered as organs at risk. For VMAT and IMPT, 78 Gy(relative biological effectiveness, RBE)/2 Gy were prescribed. The IMIT was based on 66 Gy(RBE)/20 fractions. The clinical target volume planning aims for HDR-BT ({sup 192}Ir) and LDR-BT ({sup 125}I) were D{sub 90%} ≥34 Gy in 8.5 Gy per fraction and D{sub 90%} ≥145 Gy. Both physical and RBE-weighted dose distributions for protons and carbon-ions were converted to dose distributions based on 2-Gy(IsoE) fractions. From these dose distributions various dose and dose–volume parameters were extracted. Results: Rectal wall exposure 30-70 Gy(IsoE) was reduced for IMIT, LDR-BT, and HDR-BT when compared with VMAT and IMPT. The high-dose region of the BW dose–volume histogram above 50 Gy(IsoE) of IMPT resembled the VMAT shape, whereas all other techniques showed a significantly lower high-dose region. For all 3 EBRT techniques similar urethra D{sub mean} around 74 Gy(IsoE) were obtained. The LDR-BT results were approximately 30 Gy(IsoE) higher, HDR-BT 10 Gy(IsoE) lower. Normal tissue and femoral head sparing was best with BT. Conclusion: Despite the different EBRT prescription and fractionation schemes, the high-dose regions of BW and RW expressed in Gy(IsoE) were on the same order of magnitude. Brachytherapy techniques

  18. Both F-18 FDG-avidity and Malignant Shape of Cervical Lymph Nodes on PET/CT after Total Thyroidectomy Predict Resistance to High-dose I-131 Therapy in Patients with Papillary Thyroid Cancer

    PubMed Central

    Byun, Byung Hyun; Kwon, Seong Young; Chong, Ari; Kim, Jahae; Yoo, Su Woong; Min, Jung-Joon; Song, Ho-Chun; Bom, Henry Hee-Seung

    2013-01-01

    Objective: Resistance of metastatic lymph nodes (LNs) to high dose I-131 therapy is associated with high morbidity in patients with differentiated thyroid cancer. We evaluated the role of F-18 FDG PET/CT in the prediction of resistance to high dose I-131 therapy in patients with papillary thyroid cancer. Methods: The subjects were 307 patients who underwent total or near total thyroidectomy followed by high dose (5.55-6.66 GBq) I-131 therapy. We divided the patients into three subgroups by visual assessment of regional LNs: FDG-avid LNs with a malignant shape on CT (PET/CT-positive group), FDG-avid LNs with a benign shape on CT (PET/CT-intermediate group) and no FDG-avid lesion (PET/CT-negative group). We measured the maximum SUV (SUVmax) of FDG-avid LNs in each patient. The presence or absence of focal increased uptake of I-131 was evaluated by whole body scan (WBS), and was denoted as WBS-positive group or WBS-negative group, respectively. Resistance to therapy was defined as presence of thyroglobulin (Tg) in serum (Tg ≥1.0 ng/ml) 3-6 months after I-131 therapy. Univariate and multivariate analyses were performed to determine the relationship between resistance to I-131 therapy and various clinico-pathologic variables. Results: PET/CT-positive, intermediate, and negative groups included 20 (6.5%), 44 (14.3%) and 243 (79.2%) patients, respectively. The mean SUVmax was significantly higher in the PET/CT-positive group than that of the PET/CT-intermediate group (4.6 vs. 2.7, P <0.001). Univariate analysis revealed that the PET/CT-positive group (P <0.001), T2-4 stage (P <0.001), N1b stage (P = 0.001), lower dose (5.55 GBq) of I-131 (P <0.001), and the WBS-positive group (P = 0.029) were associated with resistance to therapy. In multivariate analysis, the PET/CT-positive group, lower dose of I-131, N1b stage, and T2-4 stage remained significant with odds ratios of 10.07 (P <0.001), 3.82 (P <0.001), 3.58 (P = 0.001), and 2.53 (P = 0.009), respectively. Conclusion

  19. Single high-dose etoposide and melphalan with non-cryopreserved autologous marrow rescue as primary therapy for relapsed, refractory and poor-prognosis Hodgkin's disease.

    PubMed Central

    Seymour, L. K.; Dansey, R. D.; Bezwoda, W. R.

    1994-01-01

    A simplified schedule of high-dose chemotherapy (HDC) consisting of melphalan (140 mg m-2) plus VP16 (2.5 g m-2) given over 12-18 h together with autologous non-cryopreserved autologous bone marrow transplant (ABMT) was used for treatment of relapsed (37 patients) and refractory (seven patients) patients and as first-line treatment (four patients) for poor-prognosis Hodgkin's disease. Two patients had a second HDC-ABMT after relapse following prior HDC-ABMT, giving a total of 50 procedures among 48 patients. The haematological recovery rate was 98% with a complete response rate of the Hodgkin's disease of > 90%. Factors significantly influencing response rate were performance status and the presence of liver involvement. Thirty-nine patients are alive, with 37 in continuous complete remission. The median duration of survival and median duration of remission have not been reached at a median follow-up time of 45 months. Adverse prognostic factors for survival were disease status at the time of HDC-ABMT (refractory versus relapse, with primarily refractory patients showing significantly poor survival) and the presence of liver involvement. High-dose chemotherapy with short-duration chemotherapy and non-cryopreserved bone marrow is an effective and safe treatment modality for patients with relapsed and poor-prognosis Hodgkin's disease. PMID:8080741

  20. High-dose caspofungin as a component of combination antifungal therapy in 91 patients with neoplastic diseases and hematopoietic stem cell transplantation: a critical review of short-term and long-term adverse events.

    PubMed

    Safdar, Amar; Rodriguez, Gilhen; Zuniga, Jorge; Al Akhrass, Fadi; Pande, Anupam

    2015-04-01

    The antifungal activity of echinocandins is concentration dependent. Previously, we demonstrated that high-dose caspofungin (HD-CSP; 100 mg daily) was well tolerated in 34 immunosuppressed patients with cancer and may have favorably influenced outcomes. We retrospectively assessed all 91 patients in whom HD-CSP was given for the treatment of invasive fungal disease (IFD). The median number of doses was 18.5 ± 21.5, and in 8 (9%) patients more than 40 doses were given. Most (62%) of the patients had leukemia. A total of 45 (49%) patients had undergone stem cell transplantation; 80% received allogeneic grafts and 47% had graft-versus-host disease. High-dose corticosteroids were given during antifungal therapy in 26 (29%) patients. In all, 8 (9%) patients had new elevation in serum bilirubin during HD-CSP therapy; normalization occurred after voriconazole and HD-CSP were discontinued in 4 patients each. No other short-term or delayed adverse events were observed. In all, 40 (44%) patients died of IFD. High-dose corticosteroids during HD-CSP (odds ratio [OR] 8, 95% confidence interval [CI] 2.1-30.4; P < .002) and starting HD-CSP in the critical care unit (OR 67.5, 95% CI 5.25-868.9; P < .001) were associated with death from fungal disease. Prolonged HD-CSP therapy was well tolerated. Drug-induced hyperbilirubinemia may pose a potential limitation for continued HD-CSP use in highly susceptible patients with hematologic neoplasms and stem cell transplantation. PMID:24366977

  1. [A case of an elderly patient having advanced hepatocellular carcinoma with tumor thrombus in the inferior vena cava treated with chemo-radio-therapy--intraarterial infusion of weekly high dose 5-FU (WHF)].

    PubMed

    Yabuuchi, Shinichi; Katayose, Yu; Rikiyama, Toshiki; Oikawa, Masaya; Yamamoto, Kuniharu; Onogawa, Toru; Hayashi, Hiroki; Muto, Mitsuhisa; Unno, Michiaki

    2006-11-01

    The patient was an 81-year-old man, diagnosed with advanced huge hepatocellular carcinoma (HCC) with tumor thrombus extending into the inferior vena cava (Vv3), for which resection was judged impossible. The radio therapy (51 Gy) for tumor thrombus was carried out, and he received a weekly hepatic arterial infusion therapy (weekly high-dose 5-fluorouracil (5-FU)) for these legions. After 8 cycles, the CT scan revealed a minor response of the tumor (SD), and,the tumor marker reduced. After 10 months, these legions had markedly regressed (PR), the tumor thrombus in the inferior vena cava was not detectable. There were no severe side effects. Ten months since the start of chemo-radio therapy, the positron emission tomography (PET) revealed a metastatic tumor of the femoral bone in recurrence. In conclusion, some elderly patients of advanced HCC with tumor thrombus may obtain a long term survival through this treatment. PMID:17212102

  2. Comparison of three methods of calculation, experimental and monte carlo simulation in investigation of organ doses (thyroid, sternum, cervical vertebra) in radioiodine therapy.

    PubMed

    Shahbazi-Gahrouei, Daryoush; Ayat, Saba

    2012-07-01

    Radioiodine therapy is an effective method for treating thyroid cancer carcinoma, but it has some affects on normal tissues, hence dosimetry of vital organs is important to weigh the risks and benefits of this method. The aim of this study is to measure the absorbed doses of important organs by Monte Carlo N Particle (MCNP) simulation and comparing the results of different methods of dosimetry by performing a t-paired test. To calculate the absorbed dose of thyroid, sternum, and cervical vertebra using the MCNP code, *F8 tally was used. Organs were simulated by using a neck phantom and Medical Internal Radiation Dosimetry (MIRD) method. Finally, the results of MCNP, MIRD, and Thermoluminescent dosimeter (TLD) measurements were compared by SPSS software. The absorbed dose obtained by Monte Carlo simulations for 100, 150, and 175 mCi administered (131)I was found to be 388.0, 427.9, and 444.8 cGy for thyroid, 208.7, 230.1, and 239.3 cGy for sternum and 272.1, 299.9, and 312.1 cGy for cervical vertebra. The results of paired t-test were 0.24 for comparing TLD dosimetry and MIRD calculation, 0.80 for MCNP simulation and MIRD, and 0.19 for TLD and MCNP. The results showed no significant differences among three methods of Monte Carlo simulations, MIRD calculation and direct experimental dosimetry using TLD. PMID:23717806

  3. Comparison of Three Methods of Calculation, Experimental and Monte Carlo Simulation in Investigation of Organ Doses (Thyroid, Sternum, Cervical Vertebra) in Radioiodine Therapy

    PubMed Central

    Shahbazi-Gahrouei, Daryoush; Ayat, Saba

    2012-01-01

    Radioiodine therapy is an effective method for treating thyroid cancer carcinoma, but it has some affects on normal tissues, hence dosimetry of vital organs is important to weigh the risks and benefits of this method. The aim of this study is to measure the absorbed doses of important organs by Monte Carlo N Particle (MCNP) simulation and comparing the results of different methods of dosimetry by performing a t-paired test. To calculate the absorbed dose of thyroid, sternum, and cervical vertebra using the MCNP code, *F8 tally was used. Organs were simulated by using a neck phantom and Medical Internal Radiation Dosimetry (MIRD) method. Finally, the results of MCNP, MIRD, and Thermoluminescent dosimeter (TLD) measurements were compared by SPSS software. The absorbed dose obtained by Monte Carlo simulations for 100, 150, and 175 mCi administered 131I was found to be 388.0, 427.9, and 444.8 cGy for thyroid, 208.7, 230.1, and 239.3 cGy for sternum and 272.1, 299.9, and 312.1 cGy for cervical vertebra. The results of paired t-test were 0.24 for comparing TLD dosimetry and MIRD calculation, 0.80 for MCNP simulation and MIRD, and 0.19 for TLD and MCNP. The results showed no significant differences among three methods of Monte Carlo simulations, MIRD calculation and direct experimental dosimetry using TLD. PMID:23717806

  4. International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100).

    PubMed

    Giralt, S; Stadtmauer, E A; Harousseau, J L; Palumbo, A; Bensinger, W; Comenzo, R L; Kumar, S; Munshi, N C; Dispenzieri, A; Kyle, R; Merlini, G; San Miguel, J; Ludwig, H; Hajek, R; Jagannath, S; Blade, J; Lonial, S; Dimopoulos, M A; Einsele, H; Barlogie, B; Anderson, K C; Gertz, M; Attal, M; Tosi, P; Sonneveld, P; Boccadoro, M; Morgan, G; Sezer, O; Mateos, M V; Cavo, M; Joshua, D; Turesson, I; Chen, W; Shimizu, K; Powles, R; Richardson, P G; Niesvizky, R; Rajkumar, S V; Durie, B G M

    2009-10-01

    Multiple myeloma is the most common indication for high-dose chemotherapy with autologous stem cell support (ASCT) in North America today. Stem cell procurement for ASCT has most commonly been performed with stem cell mobilization using colony-stimulating factors with or without prior chemotherapy. The target CD34+ cell dose to be collected as well as the number of apheresis performed varies throughout the country, but a minimum of 2 million CD34+ cells/kg has been traditionally used for the support of one cycle of high-dose therapy. With the advent of plerixafor (AMD3100) (a novel stem cell mobilization agent), it is pertinent to review the current status of stem cell mobilization for myeloma as well as the role of autologous stem cell transplantation in this disease. On June 1, 2008, a panel of experts was convened by the International Myeloma Foundation to address issues regarding stem cell mobilization and autologous transplantation in myeloma in the context of new therapies. The panel was asked to discuss a variety of issues regarding stem cell collection and transplantation in myeloma especially with the arrival of plerixafor. Herein, is a summary of their deliberations and conclusions. PMID:19554029

  5. Results of a prospective phase II trial evaluating interim positron emission tomography-guided high dose therapy for poor prognosis diffuse large B-cell lymphoma.

    PubMed

    Stewart, Douglas A; Kloiber, Reinhard; Owen, Carolyn; Bahlis, Nizar J; Duggan, Peter; Mansoor, Adnan; Bence-Bruckler, Isabelle

    2014-09-01

    Patients with diffuse large B-cell lymphoma (DLBCL) with a poor prognosis based upon advanced stage and elevated serum lactate dehydrogenase achieve a 3-4-year progression-free survival (PFS) of only 55%. The role of interim fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) to guide use of upfront high dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) for patients with poor prognosis DLBCL is unproven. A prospective phase II clinical trial was designed to evaluate the outcomes of HDCT/ASCT for patients with poor prognosis DLBCL aged 18-65 years who had unfavorable interim restaging PET scans. Of the 70 eligible patients, 36 had unfavorable and 34 favorable interim PET responses, with 3-year PFS rates of 65.2% and 52.7%, respectively. In conclusion, favorable interim PET response as defined in this study is not associated with improved PFS rates for patients with poor prognosis DLBCL treated with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). A phase III trial evaluating this PET-guided approach is not warranted. PMID:24188476

  6. Prophylaxis for Pneumocystis jiroveci pneumonia: is it a necessity in pulmonary patients on high-dose, chronic corticosteroid therapy without AIDS?

    PubMed

    Liebling, Maryjane; Rubio, Edmundo; Ie, Susanti

    2015-04-01

    The benefit of prophylaxis for Pneumocystis jirovecii pneumonia (PJP) is well documented in immunocompromised patients, particularly those with HIV and/or AIDS; therefore, guidelines dictate this as standard of care. However, there is a paucity of literature regarding those without HIV and/or AIDS who are potentially predisposed to PJP, including patients with sarcoidosis, cryptogenic organizing pneumonia, interstitial lung disease, asthma and chronic obstructive pulmonary disease, who may require high dose of prolonged corticosteroids for disease maintenance or to prevent relapses. In this review, the authors examine the available literature regarding prophylaxis in these groups, elaborate on the pathogenesis of PJP, when to suspect PJP in these patients, as well as explore current recommendations that guide clinical practice regarding implementation of PJP prophylaxis, namely with trimethoprim/sulfamethoxazole being the preferred agent. In summary, the role of PJP prophylaxis in non-HIV patients on chronic steroids remains controversial. The authors present a review of the literature to provide better guidance to the clinician regarding the need to initiate PJP prophylaxis in this patient population. PMID:25771943

  7. Early Intervention with High-Dose Steroid Pulse Therapy Prolongs Disease-Free Interval of Severe Alopecia Areata: A Retrospective Study

    PubMed Central

    Yang, Chao-Chun; Lee, Chun-Te; Hsu, Chao-Kai; Lee, Yi-Pei; Wong, Tak-Wah; Chao, Sheau-Chiou; Lee, Julia Yu-Yun; Sheu, Hamm-Ming

    2013-01-01

    Background Spontaneous recovery of severe alopecia areata is rare and the condition is difficult to treat. Objective The aim of this study is to investigate and compare the effects and safety of steroid pulse therapy between oral and intravenous administrations between 1999 and 2010 at the Department of Dermatology, National Cheng Kung University Hospital. Methods Data were retrospectively retrieved. A satisfactory response was defined as more than 75% hair regrowth in the balding area. Results A total of 85 patients with more than 50% hair loss were identified and treated, with an overall satisfactory response rate of 51.8%. The mean follow-up time was 37.6 months, with a relapse rate of 22.7%. Patients with alopecia areata (hereafter, AA) of recent onset within one year showed higher response rates (p<0.001) and lower relapse rates compared to patients with AA persisting for more than 1 year. Further, even in patients with alopecia totalis, alopecia universalis or ophiasis type, early treatment resulted in a satisfactory response rate of 47% among the treated patients. In general, oral therapy was as effective and well-tolerated as intravenous therapy. Conclusion The response rate is determined by disease severity and time of intervention, not by the administration form of steroid pulse therapy. Oral steroid pulse therapy can be considered as the first-line treatment for patients with severe AA of recent onset within one year. PMID:24371395

  8. Dosimetry analyses comparing high-dose-rate brachytherapy, administered as monotherapy for localized prostate cancer, with stereotactic body radiation therapy simulated using CyberKnife.

    PubMed

    Fukuda, Shoichi; Seo, Yuji; Shiomi, Hiroya; Yamada, Yuji; Ogata, Toshiyuki; Morimoto, Masahiro; Konishi, Koji; Yoshioka, Yasuo; Ogawa, Kazuhiko

    2014-11-01

    The purpose of this study was to perform dosimetry analyses comparing high-dose-rate brachytherapy (HDR-BT) with simulated stereotactic body radiotherapy (SBRT). We selected six consecutive patients treated with HDR-BT monotherapy in 2010, and a CyberKnife SBRT plan was simulated for each patient using computed tomography images and the contouring set used in the HDR-BT plan for the actual treatment, but adding appropriate planning target volume (PTV) margins for SBRT. Then, dosimetric profiles for PTVs of the rectum, bladder and urethra were compared between the two modalities. The SBRT plan was more homogenous and provided lower dose concentration but better coverage for the PTV. The maximum doses in the rectum were higher in the HDR-BT plans. However, the HDR-BT plan provided a sharper dose fall-off around the PTV, resulting in a significant and considerable difference in volume sparing of the rectum with the appropriate PTV margins added for SBRT. While the rectum D5cm(3) for HDR-BT and SBRT was 30.7 and 38.3 Gy (P < 0.01) and V40 was 16.3 and 20.8 cm(3) (P < 0.01), respectively, SBRT was significantly superior in almost all dosimetric profiles for the bladder and urethra. These results suggest that SBRT as an alternative to HDR-BT in hypofractionated radiotherapy for prostate cancer might have an advantage for bladder and urethra dose sparing, but for the rectum only when proper PTV margins for SBRT are adopted. PMID:24957754

  9. A dosimetric analysis of intensity-modulated radiation therapy (IMRT) as an alternative to adjuvant high-dose-rate (HDR) brachytherapy in early endometrial cancer patients

    SciTech Connect

    Aydogan, Bulent . E-mail: baydogan@radonc.uchicago.edu; Mundt, Arno J.; Smith, Brett D.; Mell, Loren K.; Wang, Steve; Sutton, Harold; Roeske, John C.

    2006-05-01

    Purpose: To evaluate the role of intensity-modulated radiation treatment (IMRT) as an alternative to high-dose-rate (HDR) brachytherapy in the treatment of the vagina in postoperative early endometrial cancer patients after surgery. Methods and Materials: Planning computed tomography (CT) scans of 10 patients previously treated with HDR were used in this study. In all cases, a dose of 700 cGy/fraction was prescribed at a distance of 0.5 cm from the cylinder surface. The same CT scans were then used in IMRT planning. In this paradigm, the vaginal cylinder represents a component of a hypothetical immobilization system that would be indexed to the linac treatment table. Results: Our study showed that IMRT provided relatively lower rectal doses than HDR when treatment was prescribed at a distance of 0.5 cm away from the cylinder surface. Maximum rectal doses were lower with IMRT compared with HDR (average: 89.0% vs. 142.6%, respectively, p < 0.05). Moreover, the mean rectal dose was lower in IMRT plans compared with HDR plans with treatment prescribed either to the surface (average: 14.8% vs. 21.4%, respectively, p < 0.05) or to 0.5 cm (average: 19.6% vs. 33.5%, respectively, p < 0.05). IMRT plans had planning target volume (PTV) coverage comparable with HDR (average PTV minimum for treatment prescribed to 0.5 cm: 93.9% vs. 92.1%, p = 0.71, respectively) with less inhomogeneity (average PTV maximum: 110.8% vs. 381.6%, p < 0.05). Conclusion: Our dosimetric analysis suggests that when used in conjunction with a suitable immobilization system, IMRT may provide an alternative to HDR brachytherapy in women with early endometrial cancer after hysterectomy. However, more studies are needed to evaluate the clinical merit of the IMRT in these patients.

  10. High-dose chemotherapy and autologous stem cell support followed by post-transplant doxorubicin and taxol as initial therapy for metastatic breast cancer: hematopoietic tolerance and efficacy.

    PubMed

    deMagalhaes-Silverman, M; Hammert, L; Lembersky, B; Lister, J; Rybka, W; Ball, E

    1998-06-01

    A multistep HDC regimen was designed as first-line chemotherapy for MBC. Twenty-four patients with MBC and no previous chemotherapy for metastatic disease were treated with high-dose cyclophosphamide (5000 mg/m2), and etoposide (1000 mg/m2) (CyVP16), followed by granulocyte colony-stimulating factor (G-CSF). Peripheral blood stem cells (PBSCs) were collected. Subsequently patients received cyclophosphamide (6000 mg/m2), thiotepa (500 mg/m2) and carboplatin (800 mg/m2) (CTCb) with hematopoietic rescue. Upon recovery from hematopoietic and gastrointestinal toxicity three cycles of doxorubicin (50 mg/m2) and taxol (150 mg/m2) were delivered. After CyVP16 42% of patients developed neutropenic fevers. There was one documented episode of bacteremia. Patients received CTCb 32 days after starting CyVP16. After CTCb the median number of days to ANC >5 x 10(9)/l was 10 and to a platelet count >20 x 10(9)/l was 14. Neutropenic fevers developed in 16 patients. There were no hemorrhagic episodes. A total of 69 cycles of doxorubicin and taxol were delivered (87% of planned). The median time from PBSC infusion to the first cycle was 38 days. The median time to the second cycle was 27 days and to the last cycle was 24 days. One patient developed congestive heart failure. Two episodes of neutropenic fevers were observed. No toxicity-related deaths were observed. Grafts are stable at 6 months post transplantation. This multistep regimen is feasible with acceptable toxicity. PMID:9674853

  11. The Impact of Dose to the Bladder Trigone on Long-Term Urinary function after High-Dose Intensity-Modulated Radiation Therapy for Localized Prostate Cancer

    PubMed Central

    Ghadjar, Pirus; Zelefsky, Michael J.; Spratt, Daniel E.; af Rosenschöld, Per Munck; Oh, Jung Hun; Hunt, Margie; Kollmeier, Marisa; Happersett, Laura; Yorke, Ellen; Deasy, Joseph O.; Jackson, Andrew

    2015-01-01

    Purpose To determine the potential association between genitourinary (GU) toxicity and planning dose-volume parameters for GU pelvic structures after high-dose intensity-modulated radiotherapy (IMRT) in localized prostate cancer patients. Methods and Materials 268 patients who underwent IMRT to a prescribed dose of 86.4 Gy in 48 fractions during 06/2004–12/2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analyses were done by Kaplan-Meier method and Cox proportional hazard models, respectively. Results Median follow-up was 5 years (range, 3–7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=0.006), the V90 of the trigone (P=0.006), and the maximal dose to the trigone (P=0.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=0.009) and increased maximal dose to the trigone (P=0.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high-risk and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low-risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk (29%) and 5 of 68 low-risk (7%) patients experienced an IPSS sum increase ≥10 (P=0.001; odds ratio, 5.19). Conclusions The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the bladder trigone appears to be associated with a reduction in late

  12. Evaluation of intranasal vaccine administration and high-dose interferon- α2b therapy for treatment of chronic upper respiratory tract infections in shelter cats.

    PubMed

    Fenimore, Audra; Carter, Kasey; Fankhauser, Jeffrey; Hawley, Jennifer R; Lappin, Michael R

    2016-08-01

    Clinical signs of upper respiratory tract infection can be hard to manage in cats, particularly those in shelters. In this study, clinical data were collected from chronically ill (3-4 weeks' duration) cats with suspected feline herpesvirus-1 (FHV-1) or feline calicivirus (FCV) infections after administration of one of two novel therapies. Group A cats were administered a commercially available formulation of human interferon-α2b at 10,000 U/kg subcutaneously for 14 days, and group B cats were administered one dose of a FHV-1 and FCV intranasal vaccine. Molecular assays for FHV-1 and FCV were performed on pharyngeal samples, and a number of cytokines were measured in the blood of some cats. A clinical score was determined daily for 14 days, with cats that developed an acceptable response by day 14 returning to the shelter for adoption. Those failing the first treatment protocol were entered into the alternate treatment group. During the first treatment period, 8/13 cats in group A (61.5%) and all 12 cats in group B (100%) had apparent responses. The seven cats positive for nucleic acids of FHV-1 or FCV responded favorably, independent of the treatment group. There were no differences in cytokine levels between cats that responded to therapy or failed therapy. Either protocol assessed here may be beneficial in alleviating chronic clinical signs of suspected feline viral upper respiratory tract disease in some cats that have failed other, more conventional, therapies. The results of this study warrant additional research involving these protocols. PMID:26269455

  13. Feasibility and efficacy of high-dose three-dimensional-conformal radiotherapy in cirrhotic patients with small-size hepatocellular carcinoma non-eligible for curative therapies-mature results of the French Phase II RTF-1 trial

    SciTech Connect

    Mornex, Francoise . E-mail: francoise.mornex@chu-lyon.fr; Girard, Nicolas; Beziat, Christophe; Kubas, Abdul; Khodri, Mustapha; Trepo, Christian; Merle, Philippe

    2006-11-15

    Purpose: Hepatocellular carcinoma (HCC) is a poor prognosis tumor, and only 20% of patients will benefit from curative therapies (surgery, liver transplantation, percutaneous ablation). Although conventional radiotherapy has been traditionally regarded as inefficient and toxic for cirrhotic patients, three-dimensional conformal radiotherapy (3DCRT) has provided promising preliminary data for the treatment of HCC. Methods and Materials: Prospective phase II trial including Child-Pugh A/B cirrhotic patients with small-size HCC (1 nodule {<=}5 cm, or 2 nodules {<=}3 cm) nonsuitable for curative treatments, to assess tolerance and efficacy of high-dose (66 Gy, 2 Gy/fraction) 3DCRT. Results: Twenty-seven patients were enrolled. Among the 25 assessable patients, tumor response was observed for 23 patients (92%), with complete response for 20 patients (80%), and partial response for 3 patients (12%). Stable disease was observed in 2 patients (8%). Grade 4 toxicities occurred in 2 of 11 (22%) Child-Pugh B patients only. Child-Pugh A patients tolerated treatment well, and 3/16 (19%) developed asymptomatic Grade 3 toxicities. Conclusion: High-dose 3DCRT is a noninvasive, well-tolerated modality that is highly suitable for the treatment of small HCCs in cirrhotic patients, with promising results. However, additional trials are needed to optimize this technique and formally compare it with the usual curative approaches.

  14. Randomized Noninferiority Trial of Reduced High-Dose Volume Versus Standard Volume Radiation Therapy for Muscle-Invasive Bladder Cancer: Results of the BC2001 Trial (CRUK/01/004)

    SciTech Connect

    Huddart, Robert A.; Hall, Emma; Hussain, Syed A.; Jenkins, Peter; Rawlings, Christine; Tremlett, Jean; Crundwell, Malcolm; Adab, Fawzi A.; Sheehan, Denise; Syndikus, Isabel; Hendron, Carey; Lewis, Rebecca; Waters, Rachel; James, Nicholas D.

    2013-10-01

    Purpose: To test whether reducing radiation dose to uninvolved bladder while maintaining dose to the tumor would reduce side effects without impairing local control in the treatment of muscle-invasive bladder cancer. Methods and Materials: In this phase III multicenter trial, 219 patients were randomized to standard whole-bladder radiation therapy (sRT) or reduced high-dose volume radiation therapy (RHDVRT) that aimed to deliver full radiation dose to the tumor and 80% of maximum dose to the uninvolved bladder. Participants were also randomly assigned to receive radiation therapy alone or radiation therapy plus chemotherapy in a partial 2 × 2 factorial design. The primary endpoints for the radiation therapy volume comparison were late toxicity and time to locoregional recurrence (with a noninferiority margin of 10% at 2 years). Results: Overall incidence of late toxicity was less than predicted, with a cumulative 2-year Radiation Therapy Oncology Group grade 3/4 toxicity rate of 13% (95% confidence interval 8%, 20%) and no statistically significant differences between groups. The difference in 2-year locoregional recurrence free rate (RHDVRT − sRT) was 6.4% (95% confidence interval −7.3%, 16.8%) under an intention to treat analysis and 2.6% (−12.8%, 14.6%) in the “per-protocol” population. Conclusions: In this study RHDVRT did not result in a statistically significant reduction in late side effects compared with sRT, and noninferiority of locoregional control could not be concluded formally. However, overall low rates of clinically significant toxicity combined with low rates of invasive bladder cancer relapse confirm that (chemo)radiation therapy is a valid option for the treatment of muscle-invasive bladder cancer.

  15. Serum PCSK9 Levels Distinguish Individuals Who Do Not Respond to High-Dose Statin Therapy with the Expected Reduction in LDL-C

    PubMed Central

    Taylor, Beth A.; Panza, Gregory; Pescatello, Linda S.; Chipkin, Stuart; Gipe, Daniel; Shao, Weiping; White, C. Michael; Thompson, Paul D.

    2014-01-01

    The purpose of the present report was to examine whether proprotein convertase subtilisin/kexin type 9 (PCSK9) levels differ in individuals who do not exhibit expected reductions in low density lipoprotein cholesterol (LDL-C) with statin therapy. Eighteen nonresponder subjects treated with 80 mg atorvastatin treatment for 6 months without substantial reductions in LDL-C (ΔLDL-C: 2.6 ± 11.4%) were compared to age- and gender-matched atorvastatin responders (ΔLDL-C: 50.7 ± 8.5%) and placebo-treated subjects (ΔLDL-C: 9.9 ± 21.5%). Free PCSK9 was marginally higher in nonresponders at baseline (P = 0.07) and significantly higher in atorvastatin responders after 6 months of treatment (P = 0.04). The change in free PCSK9 over 6 months with statin treatment was higher (P < 0.01) in atorvastatin responders (134.2 ± 131.5 ng/mL post- versus prestudy) than in either the nonresponders (39.9 ± 87.8 ng/mL) or placebo subjects (27.8 ± 97.6 ng/mL). Drug compliance was not lower in the nonresponders as assessed by pill counts and poststudy plasma atorvastatin levels. Serum PCSK9 levels, both at baseline and in response to statin therapy, may differentiate individuals who do versus those who do not respond to statin treatment. PMID:25136459

  16. Radioiodine and radiotherapy in the management of thyroid cancers

    SciTech Connect

    Simpson, W.J. )

    1990-06-01

    Radioiodine is an important adjuvant treatment in the management of resectable papillary and follicular thyroid cancers in all patients except those with the best prognostic features. External radiation is also an important adjuvant therapy in these patients, especially those with tumors that extend beyond the thyroid gland and invade the trachea, esophagus, nerves, and blood vessels; it is especially important in treating patients whose tumors do not concentrate radioiodine. Radioiodine may be curative in patients with microscopic distant metastases demonstrated by radioiodine scanning. Even unresectable primary papillary and follicular cancers may be eradicated by combined therapy with radioiodine and radiotherapy. Radioiodine plays no significant role in the treatment of medullary or anaplastic thyroid cancers, but external radiation may eradicate microscopic thyroid bed or nodal disease when persistent disease is indicated by elevated calcitonin levels in medullary thyroid cancer patients. Anaplastic thyroid cancers are usually unresectable and are not eradicated by conventional radiotherapy or by any of the novel radiation techniques, with or without chemotherapy. In all types of thyroid cancer, external radiotherapy may produce beneficial palliative results in patients with distant metastases, but the use of radioiodine should always be explored in papillary and follicular thyroid cancer patients. 30 references.

  17. Direct exposure of mouse ovaries and oocytes to high doses of an adenovirus gene therapy vector fails to lead to germ cell transduction.

    PubMed

    Gordon, J W

    2001-04-01

    The risk of insertion of adenovirus gene therapy DNA into female germ cells during the course of somatic gene therapy was stringently tested in the mouse by injecting up to 10(10) infectious particles directly into the ovary and by incubating naked oocytes in a solution of 2 x 10(8) particles/ml for 1 h prior to in vitro fertilization (IVF). The vector used was a recombinant adenovirus carrying the bacterial lacZ gene driven by the cytomegalovirus promoter (Adbeta-gal). Ovaries were stained for LacZ activity, or immunochemically for LacZ, 5-7 days after injection. Although very large amounts of LacZ activity and protein were detected, all positive staining was in the thecal portion of the ovary, with no staining seen in oocytes. In another series of experiments, mice with injected ovaries were mated, and preimplantation embryos or fetuses were analyzed either for LacZ expression or by PCR for lacZ DNA. None of 202 preimplantation embryos stained positively for LacZ and none of 58 fetuses were positive for DNA by PCR analysis. Finally, more than 1400 eggs were fertilized after exposure to the vector prior to IVF and stained as morulae for LacZ activity. Fewer than 2% of the embryos stained positively for LacZ, and experiments indicated that the staining was due to incomplete washing of the eggs prior to IVF. These data provide strong evidence that adenoviruses cannot infect oocytes and that the risk of female germ-line transduction with such vectors is very low. PMID:11319918

  18. External-Beam Radiation Therapy and High-Dose Rate Brachytherapy Combined With Long-Term Androgen Deprivation Therapy in High and Very High Prostate Cancer: Preliminary Data on Clinical Outcome

    SciTech Connect

    Martinez-Monge, Rafael; Moreno, Marta; Ciervide, Raquel; Cambeiro, Mauricio; Perez-Gracia, Jose Luis; Gil-Bazo, Ignacio; Gaztanaga, Miren; Arbea, Leire; Pascual, Ignacio; Aristu, Javier

    2012-03-01

    Purpose: To determine the feasibility of combined long-term androgen deprivation therapy (ADT) and dose escalation with high-dose-rate (HDR) brachytherapy. Methods and Materials: Between 2001 and 2007, 200 patients with high-risk prostate cancer (32.5%) or very high-risk prostate cancer (67.5%) were prospectively enrolled in this Phase II trial. Tumor characteristics included a median pretreatment prostate-specific antigen of 15.2 ng/mL, a clinical stage of T2c, and a Gleason score of 7. Treatment consisted of 54 Gy of external irradiation (three-dimensional conformal radiotherapy [3DCRT]) followed by 19 Gy of HDR brachytherapy in four twice-daily treatments. ADT started 0-3 months before 3DCRT and continued for 2 years. Results: One hundred and ninety patients (95%) received 2 years of ADT. After a median follow-up of 3.7 years (range, 2-9), late Grade {>=}2 urinary toxicity was observed in 18% of the patients and Grade {>=}3 was observed in 5%. Prior transurethral resection of the prostate (p = 0.013) and bladder D{sub 50} {>=}1.19 Gy (p = 0.014) were associated with increased Grade {>=}2 urinary complications; age {>=}70 (p = 0.05) was associated with Grade {>=}3 urinary complications. Late Grade {>=}2 gastrointestinal toxicity was observed in 9% of the patients and Grade {>=}3 in 1.5%. CTV size {>=}35.8 cc (p = 0.007) and D{sub 100} {>=}3.05 Gy (p = 0.01) were significant for increased Grade {>=}2 complications. The 5-year and 9-year biochemical relapse-free survival (nadir + 2) rates were 85.1% and 75.7%, respectively. Patients with Gleason score of 7-10 had a decreased biochemical relapse-free survival (p = 0.007). Conclusions: Intermediate-term results at the 5-year time point indicate a favorable outcome without an increase in the rate of late complications.

  19. X-ray induced Sm3+ to Sm2+ conversion in fluorophosphate and fluoroaluminate glasses for the monitoring of high-doses in microbeam radiation therapy

    NASA Astrophysics Data System (ADS)

    Vahedi, Shahrzad; Okada, Go; Morrell, Brian; Muzar, Edward; Koughia, Cyril; Edgar, Andy; Varoy, Chris; Belev, George; Wysokinski, Tomasz; Chapman, Dean; Kasap, Safa

    2012-10-01

    Fluorophosphate and fluoroaluminate glasses doped with trivalent samarium were evaluated as sensors of x-ray radiation for microbeam radiation therapy at the Canadian Light Source using the conversion of trivalent Sm3+ to the divalent form Sm2+. Both types of glasses show similar conversion rates and may be used as a linear sensor up to ˜150 Gy and as a nonlinear sensor up to ˜2400 Gy, where saturation is reached. Experiments with a multi-slit collimator show high spatial resolution of the conversion pattern; the pattern was acquired by a confocal fluorescence microscopy technique. The effects of previous x-ray exposure may be erased by annealing at temperatures exceeding the glass transition temperature Tg while annealing at TA < Tg enhances the Sm conversion. This enhancement is explained by a thermally stimulated relaxation of host glass ionic matrix surrounding x-ray induced Sm2+ ions. In addition, some of the Sm3+-doped glasses were codoped with Eu2+-ions but the results show that there is no marked improvement in the conversion efficiency by the introduction of Eu2+.

  20. Radioiodine-induced thyroid storm. Case report and literature review

    SciTech Connect

    McDermott, M.T.; Kidd, G.S.; Dodson, L.E. Jr.; Hofeldt, F.D.

    1983-08-01

    Thyroid storm developed following radioiodine therapy in a 43-year-old man with Graves' disease, weight loss, myopathy, severe thyrotoxic hypercalcemia, and a pituitary adenoma. The hypercalcemia may have been a significant, and previously unreported, predisposing factor for the radioiodine-associated thyroid storm. This case and 15 other well-documented cases of radioiodine-associated storm found in the literature are reviewed, as are several other cases of less severe exacerbations of thyrotoxicosis associated with radioiodine therapy. Although not often seen, these complications are often fatal. High-risk patients, such as the elderly, those with severe thyrotoxicosis, and those with significant underlying diseases, may benefit from preventive measures such as the judicious use of thyrostatic medications during the periods before and after isotope administration.

  1. High-Dose Hypofractionated Proton Beam Radiation Therapy Is Safe and Effective for Central and Peripheral Early-Stage Non-Small Cell Lung Cancer: Results of a 12-Year Experience at Loma Linda University Medical Center

    SciTech Connect

    Bush, David A.; Cheek, Gregory; Zaheer, Salman; Wallen, Jason; Mirshahidi, Hamid; Katerelos, Ari; Grove, Roger; Slater, Jerry D.

    2013-08-01

    Purpose: We update our previous reports on the use of hypofractionated proton beam radiation therapy for early-stage lung cancer patients. Methods and Materials: Eligible subjects had biopsy-proven non-small cell carcinoma of the lung and were medically inoperable or refused surgery. Clinical workup required staging of T1 or T2, N0, M0. Subjects received hypofractionated proton beam therapy to the primary tumor only. The dose delivered was sequentially escalated from 51 to 60 Gy, then to 70 Gy in 10 fractions over 2 weeks. Endpoints included toxicity, pulmonary function, overall survival (OS), disease-specific survival (DSS), and local control (LC). Results: One hundred eleven subjects were analyzed for treatment outcomes. The patient population had the following average characteristics; age 73.2 years, tumor size 3.6 cm, and 1.33 L forced expiratory volume in 1 second. The entire group showed improved OS with increasing dose level (51, 60, and 70 Gy) with a 4-year OS of 18%, 32%, and 51%, respectively (P=.006). Peripheral T1 tumors exhibited LC of 96%, DSS of 88%, and OS of 60% at 4 years. Patients with T2 tumors showed a trend toward improved LC and survival with the 70-Gy dose level. On multivariate analysis, larger tumor size was strongly associated with increased local recurrence and decreased survival. Central versus peripheral location did not correlate with any outcome measures. Clinical radiation pneumonitis was not found to be a significant complication, and no patient required steroid therapy after treatment for radiation pneumonitis. Pulmonary function was well maintained 1 year after treatment. Conclusions: High-dose hypofractionated proton therapy achieves excellent outcomes for lung carcinomas that are peripherally or centrally located. The 70-Gy regimen has been adopted as standard therapy for T1 tumors at our institution. Larger T2 tumors show a trend toward improved outcomes with higher doses, suggesting that better results could be seen with

  2. High-dose cytosine-arabinoside and cisplatin regimens as salvage therapy for refractory or relapsed AIDS-related non-Hodgkin's lymphoma.

    PubMed

    Bi, J; Espina, B M; Tulpule, A; Boswell, W; Levine, A M

    2001-12-15

    No effective salvage regimen has been defined for patients with AIDS-related non-Hodgkin's lymphoma (AIDS-NHL) who do not respond to first-line chemotherapy that contains anthracycline. Combined dexamethasone, cytosine arabinoside, and cisplatin (DHAP) and etoposide, methylprednisolone, cytosine arabinoside, and cisplatin (ESHAP) have shown good response rates in HIV-negative patients with relapsed lymphomas. We retrospectively analyzed patients with refractory or relapsed AIDS-NHL who had been treated with either DHAP or ESHAP to evaluate the feasibility and efficacy of these regimens. Twenty-six patients with refractory or relapsed AIDS-NHL were treated between 1990 and 1999 either with DHAP ( n = 13) or with ESHAP ( n = 13). Only 1 patient from each group (8%) had achieved complete remission with any previous therapy, and most had progressive disease after the regimen immediately preceding DHAP or ESHAP. In the ESHAP group, 4 patients (31%) achieved complete remission (CR) and 3 patients (23%) attained partial remission (PR) for an overall response rate of 54%. The median survival was 7.1 months (range, 1-58.9+ months) from the time ESHAP was begun. Among the 3 patients with primary refractory lymphoma, there was 1 CR, 1 PR, and one patient with stable disease. In contrast, only 1 PR (7%) was observed with DHAP; the median survival was 3 months. Myelosuppression was the most significant toxicity with grade 4 neutropenia occurring in all who received ESHAP and in 54% of patients treated with DHAP. Neutropenic fever occurred in 8 (62%) ESHAP-treated and 6 (46%) DHAP-treated patients. Although hematologic toxicity is profound, ESHAP appears to be an active salvage regimen for patients with relapsed or refractory AIDS-NHL. PMID:11744828

  3. Indirect Tumor Cell Death After High-Dose Hypofractionated Irradiation: Implications for Stereotactic Body Radiation Therapy and Stereotactic Radiation Surgery

    SciTech Connect

    Song, Chang W.; Lee, Yoon-Jin; Griffin, Robert J.; Park, Inhwan; Koonce, Nathan A.; Hui, Susanta; Kim, Mi-Sook; Dusenbery, Kathryn E.; Sperduto, Paul W.; Cho, L. Chinsoo

    2015-09-01

    Purpose: The purpose of this study was to reveal the biological mechanisms underlying stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS). Methods and Materials: FSaII fibrosarcomas grown subcutaneously in the hind limbs of C3H mice were irradiated with 10 to 30 Gy of X rays in a single fraction, and the clonogenic cell survival was determined with in vivo–in vitro excision assay immediately or 2 to 5 days after irradiation. The effects of radiation on the intratumor microenvironment were studied using immunohistochemical methods. Results: After cells were irradiated with 15 or 20 Gy, cell survival in FSaII tumors declined for 2 to 3 days and began to recover thereafter in some but not all tumors. After irradiation with 30 Gy, cell survival declined continuously for 5 days. Cell survival in some tumors 5 days after 20 to 30 Gy irradiation was 2 to 3 logs less than that immediately after irradiation. Irradiation with 20 Gy markedly reduced blood perfusion, upregulated HIF-1α, and increased carbonic anhydrase-9 expression, indicating that irradiation increased tumor hypoxia. In addition, expression of VEGF also increased in the tumor tissue after 20 Gy irradiation, probably due to the increase in HIF-1α activity. Conclusions: Irradiation of FSaII tumors with 15 to 30 Gy in a single dose caused dose-dependent secondary cell death, most likely by causing vascular damage accompanied by deterioration of intratumor microenvironment. Such indirect tumor cell death may play a crucial role in the control of human tumors with SBRT and SRS.

  4. Computer-aided detection of therapy-induced leukoencephalopathy in pediatric acute lymphoblastic leukemia patients treated with intravenous high-dose methotrexate.

    PubMed

    Glass, John O; Reddick, Wilburn E; Li, Chin-Shang; Laningham, Fred H; Helton, Kathleen J; Pui, Ching-Hon

    2006-07-01

    The purpose of this study was to use objective quantitative magnetic resonance imaging (MRI) methods to develop a computer-aided detection (CAD) tool to differentiate white matter (WM) hyperintensities into either leukoencephalopathy (LE) induced by chemotherapy or normal maturational processes in children treated for acute lymphoblastic leukemia without irradiation. A combined MRI set consisting of T1-weighted, T2-weighted, proton-density-weighted and fluid-attenuated inversion recovery images and WM, gray matter and cerebrospinal fluid proportional volume maps from a spatially normalized atlas were analyzed with a neural network segmentation based on a Kohonen self-organizing map (SOM). Segmented maps were manually classified to identify the most hyperintense WM region and the normal-appearing genu region. Signal intensity differences normalized to the genu within each examination were generated for four time points in 228 children. A second Kohonen SOM was trained on the first examination data and divided the WM into normal-appearing or LE groups. Reviewing labels from the CAD tool revealed a consistency measure of 89.8% (167 of 186) within patients. The overall agreement between the CAD tool and the consensus reading of two trained observers was 84.1% (535 of 636), with 84.2% (170 of 202) agreement in the training set and 84.1% (365 of 434) agreement in the testing set. These results suggest that subtle therapy-induced LE can be objectively and reproducibly detected in children treated for cancer using this CAD approach based on relative differences in quantitative signal intensity measures normalized within each examination. PMID:16824973

  5. Effective method of measuring the radioactivity of [131I]-capsule prior to radioiodine therapy with significant reduction of the radiation exposure to the medical staff.

    PubMed

    Lützen, Ulf; Zhao, Yi; Marx, Malies; Imme, Thea; Assam, Isong; Siebert, Frank-Andre; Culman, Juaraj; Zuhayra, Maaz

    2016-01-01

    Radiation Protection in Radiology, Nuclear Medicine and Radio Oncology is of the utmost importance. Radioiodine therapy is a frequently used and effective method for the treatment of thyroid disease. Prior to each therapy the radioactivity of the [131I]-capsule must be determined to prevent misadministration. This leads to a significant radiation exposure to the staff. We describe an alternative method, allowing a considerable reduction of the radiation exposure. Two [131I]-capsules (A01 = 2818.5; A02 = 7355.0 MBq) were measured multiple times in their own delivery lead containers - that is to say, [131I]-capsules remain inside the containers during the measurements (shielded measurement) using a dose calibrator and a well-type and a thyroid uptake probe. The results of the shielded measurements were correlated linearly with the [131I]-capsules radioactivity to create calibration curves for the used devices. Additional radioactivity measurements of 50 [131I]-capsules of different radioactivities were done to validate the shielded measuring method. The personal skin dose rate (HP(0.07)) was determined using calibrated thermo luminescent dosimeters. The determination coefficients for the calibration curves were R2 > 0.9980 for all devices. The relative uncertainty of the shielded measurement was < 6.8%. At a distance of 10 cm from the unshielded capsule the HP(0.07) was 46.18 μSv/(GBq•s), and on the surface of the lead container containing the [131I]-capsule the HP(0.07) was 2.99 and 0.27 μSv/(GBq•s) for the two used container sizes. The calculated reduction of the effective dose by using the shielded measuring method was, depending on the used container size, 74.0% and 97.4%, compared to the measurement of the unshielded [131I]-capsule using a dose calibrator. The measured reduction of the effective radiation dose in the practice was 56.6% and 94.9 for size I and size II containers. The shielded [131I]-capsule measurement reduces the radiation exposure to the

  6. The incidence of ophthalmopathy after radioiodine therapy for Graves` disease: Prognostic factors and the role of methimazole

    SciTech Connect

    Kung, A.W.C.; Cheng, A.

    1994-08-01

    Radioactive iodine-131 (RAI) has been reported to be associated with a high incidence of development or exacerbation of Graves` ophthalmopathy (GO). This is thought to be associated with a surge of autoantibodies after RAI therapy. The role of methimazole (MMI), which possesses immunomodulatory action, in the prevention of GO was explored by studying 114 patients with Graves` disease. They were assigned randomly to receive either RAI alone or adjunctive antithyroid drugs, which consisted of MMI and L-T{sub 4} as a block-replacement therapy for 12 months and were followed for 2 yr. Thirty-five patients (30.7%) had GO at presentation. Twenty-one (18%) patients developed new GO, and six had worsening of preexisting GO. The development of hypothyroidism (P < 0.01) and an elevation of TSH (P < 0.05) were associated with increased risk of development or exacerbation of GO. The chance of development or exacerbation of GO is higher in those with no ophthalmopathy than in those with preexisting GO at presentation (P = 0.002). The incidence of development or exacerbation of GO was similar in the two treatment groups (RAI, 22.8%; adjunctive antithyroid drugs, 23.7%; P = NS). MMI was able to suppress the surge of TSH receptor antibody (TRAB) after RAI, but a surge in TRAB was not of prognostic significance for the development of GO after RAI. Patients who developed or had exacerbation of GO actually had lower TRAB at presentation (P = 0.02). The authors conclude that hypothyroidism with elevated TSH is an important adverse factor for the development or exacerbation of GO, and MMI was unable to prevent the development or exacerbation of GO after RAI. 35 refs., 4 tabs.

  7. Modification of a motel-type room to accommodate patients receiving radioiodine therapy: reduction of environmental exposure.

    PubMed

    Pickering, Charles A; Dykes, James N; Domingo, Michelle T; Patricko, Joseph; Yamauchi, Dave M; Williams, Lawrence E

    2012-08-01

    Patients receiving ¹³¹I-based therapies are generally restricted in leaving the medical institution. In the U.S., the U.S. Nuclear Regulatory Commission (U.S. NRC) has developed the rule that a ≤ 7 mR h⁻¹ reading at 1 m from the patient (or 33 mCi) is sufficient to allow unrestricted release. Because of home situations and other constraints, it is preferable that a patient-specific release level be determined by the radiation safety staff. Locally, the City of Hope has instituted a general release criterion of ≤ 2 mR h⁻¹ at 1 m. While contributing to a reduction in public exposure, this as low as reasonably achievable (ALARA) approach is difficult to justify on a cost basis due to the expense of maintaining the radioactive individual in a hospital room. Instead, it was determined that a motel-type room already on the campus be modified to allow the patient to remain on-site until at or below a locally permitted release level. By adding lead to the bathroom area and sealing the tile surfaces, the room may be converted for less than $5,000. Daily cost for the patient is $65. In comparing the use of this facility for thyroid cancer patients from 2006 to 2010, it was found that the public exposure at 1 m was reduced by approximately 70% as compared to release at the 7 mR h level. In addition, controlling the release reduces the likelihood of a radiation incident in the public environment such as on public transportation or in a hotel. PMID:22739966

  8. Radioiodinated branched carbohydrates

    DOEpatents

    Goodman, Mark M.; Knapp, Jr., Furn F.

    1989-01-01

    A radioiodinated branched carbohydrate for tissue imaging. Iodine-123 is stabilized in the compound by attaching it to a vinyl functional group that is on the carbohydrate. The compound exhibits good uptake and retention and is promising in the development of radiopharmaceuticals for brain, heart and tumor imaging.

  9. Radioiodine: the classic theranostic agent.

    PubMed

    Silberstein, Edward B

    2012-05-01

    Radioiodine has the distinction of being the first theranostic agent in our armamentarium. Millennia were required to discover that the agent in orally administered seaweed and its extracts, which had been shown to cure neck swelling due to thyromegaly, was iodine, first demonstrated to be a new element in 1813. Treatment of goiter with iodine began at once, but its prophylactic value to prevent a common form of goiter took another century. After Enrico Fermi produced the first radioiodine, (128)I, in 1934, active experimentation in the United States and France delineated the crucial role of iodine in thyroid metabolism and disease. (130)I and (131)I were first employed to treat thyrotoxicosis by 1941, and thyroid cancer in 1943. After World War II, (131)I became widely available at a reasonable price for diagnostic testing and therapy. The rectilinear scanner of Cassen and Curtis (Science 1949;110:94-95), and a dedicated gamma camera invented by Anger (Nature 1952;170:200-201), finally permitted the diagnostic imaging of thyroid disease, with (131)I again the radioisotope of choice, although there were short-lived attempts to employ (125)I and (132)I for this purpose. (123)I was first produced in 1949 but did not become widely available until about 1982, 10 years after a production technique eliminated high-energy (124)I contamination. I continues to be the radioiodine of choice for the diagnosis of benign thyroid disease, whereas (123)I and (131)I are employed in the staging and detection of functioning thyroid cancer. (124)I, a positron emitter, can produce excellent anatomically correlated images employing positron emission tomography/computed tomography equipment and has the potential to enhance heretofore imperfect dosimetric studies in determining the appropriate administered activity to ablate/treat thyroid cancer. Issues of acceptable measuring error in thyroid cancer dosimetry and the role in (131)I therapy of tumor heterogeneity, tumor hypoxia, and

  10. High-dose-rate brachytherapy and hypofractionated external beam radiotherapy combined with long-term hormonal therapy for high-risk and very high-risk prostate cancer: outcomes after 5-year follow-up

    PubMed Central

    Ishiyama, Hiromichi; Satoh, Takefumi; Kitano, Masashi; Tabata, Ken-ichi; Komori, Shouko; Ikeda, Masaomi; Soda, Itaru; Kurosaka, Shinji; Sekiguchi, Akane; Kimura, Masaki; Kawakami, Shogo; Iwamura, Masatsugu; Hayakawa, Kazushige

    2014-01-01

    The purpose of this study was to report the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) for National Comprehensive Cancer Network (NCCN) criteria-defined high-risk (HR) and very high-risk (VHR) prostate cancer. Data from 178 HR (n = 96, 54%) and VHR (n = 82, 46%) prostate cancer patients who underwent 192Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed. The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After five fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administered. All patients initially underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT was continued for 36 months after EBRT. The median follow-up was 61 months (range, 25–94 months) from the start of radiotherapy. The 5-year biochemical non-evidence of disease, freedom from clinical failure and overall survival rates were 90.6% (HR, 97.8%; VHR, 81.9%), 95.2% (HR, 97.7%; VHR, 92.1%), and 96.9% (HR, 100%; VHR, 93.3%), respectively. The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3% of patients and Grade 3 in 9.6%. The highest late gastrointestinal toxicities were Grade 2 in 2.8% of patients and Grade 3 in 0%. Although the 5-year outcome of this tri-modality approach seems favorable, further follow-up is necessary to validate clinical and survival advantages of this intensive approach compared with the standard EBRT approach. PMID:24222312

  11. Impact of high-dose chemotherapy and autologous transplantation as first-line therapy on the survival of high-risk diffuse large B cell lymphoma patients: a single-center study in Japan.

    PubMed

    Inano, Shojiro; Iwasaki, Makoto; Iwamoto, Yoshihiro; Sueki, Yuki; Fukunaga, Akiko; Yanagita, Soshi; Arima, Nobuyoshi

    2014-02-01

    High-dose chemotherapy (HDT), together with autologous stem cell transplantation (ASCT), plays an important role in the treatment of diffuse large B cell lymphoma (DLBCL), especially as second-line therapy. However, its significance in up-front settings remains to be elucidated. In our institute, patients with DLBCL in both the high-intermediate and high international prognostic index (IPI) groups initially underwent CHOP/R-CHOP treatment followed by HDT/ASCT at upfront settings between 2002 and 2011. We retrospectively analyzed 25 patients who were all treated with upfront HDT/ASCT. We excluded one patient who failed to undergo transplantation because of primary refractory disease from the analysis. The median follow-up was 77 months (range 17-110 months). Five-year overall survival (OS) and progression-free survival (PFS) were 91.7 and 79.2 %, respectively, which were higher than the equivalents in previous studies. The OS and PFS in the high-risk group were lower than those in the high-intermediate group. Treatment-related mortalities or fatal complication were not observed. Our results confirm that HDT/ASCT for high-risk aggressive lymphoma is a feasible and promising therapy, but patients with high IPI continued to have poor prognoses; improvements in treatment strategy are clearly needed. Since HDT/ASCT is an aggressive treatment option associated with long-term complications, we need to identify patient groups that will gain the maximum benefit from HDT/ASCT in the upfront setting. PMID:24338743

  12. CHOP versus CHOP plus ESHAP and high-dose therapy with autologous peripheral blood progenitor cell transplantation for high-intermediate-risk and high-risk aggressive non-Hodgkin's lymphoma.

    PubMed

    Intragumtornchai, T; Prayoonwiwat, W; Numbenjapon, T; Assawametha, N; O'Charoen, R; Swasdikul, D

    2000-12-01

    The purpose of the study was to compare conventional cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP) chemotherapy with CHOP (3 courses) plus etoposide/methylprednisolone/high-dose cytarabine/cisplatin (ESHAP), high-dose therapy (HDT), and autologous peripheral blood progenitor cell transplantation (PBPCT) as front-line treatment for poor-prognosis aggressive non-Hodgkin's lymphoma (NHL). Between May 1, 1995, and April 30, 1998, 58 patients, aged 15-55 years, newly diagnosed with poor-prognosis aggressive NHL (category F-H by the Working Formulation) were enrolled. According to the age-adjusted international prognostic index, 65% of the patients were high-risk cases and 35% made up the high-intermediate group. After 3 courses of CHOP, 25 of 48 patients were randomized to continue with CHOP, and 23 were randomized to receive 2-4 cycles of ESHAP followed by HDT and PBPCT. There was no significant difference in the rate of complete remission between the two groups (36%, 95% confidence interval [CI]: 18%-57% in CHOP vs. 43%, 95% CI: 23%-65% in ESHAP/HDT) (P = 0.77). With a median follow-up duration of 39 months, the 4-year failure-free survival (FFS) was superior in the ESHAP/HDT group (38%, 95% CI: 18%-58% vs. 15%, 95% CI: 4%-32%) (P = 0.04). The disease-free survival was marginally different in favor of the ESHAP/HDT arm (90%, 95% CI: 47%-98% vs. 37%, 95% CI: 7%-69%) (P = 0.06). The 4-year overall survival between the two treatment arms was comparable (51%, 95% CI: 28%-70% for ESHAP/HDT vs. 30%, 95% CI: 13%-48% for CHOP) (P = 0.25). Treatment-related mortalities were not significantly different between both groups (17%, 95% CI: 5%-39% for ESHAP/HDT vs. 8%, 95% CI: 1%-26% for CHOP) (P = 0.41). However, only 61% of the patients assigned to the ESHAP/HDT arm underwent HDT and PBPCT. As compared with CHOP, the corporate regimen of CHOP/ESHAP/HDT seems to improve the FFS in patients with newly diagnosed, poor-prognosis aggressive NHL. PMID:11707834

  13. Patterns and Predictors of Amelioration of Genitourinary Toxicity after High-Dose Intensity-Modulated Radiation Therapy for Localized Prostate Cancer: Implications for Defining Post-Radiotherapy Urinary Toxicity

    PubMed Central

    Ghadjar, Pirus; Jackson, Andrew; Spratt, Daniel E.; Oh, Jung Hun; Rosenschöld, Per Munck af; Kollmeier, Marisa; Yorke, Ellen; Hunt, Margie; Deasy, Joseph O.; Zelefsky, Michael J.

    2016-01-01

    Background Treatment-related toxicity and quality of life (QoL) considerations are important when counseling patients with localized prostate cancer. Objective To determine the incidence and longitudinal pattern of late genitourinary (GU) toxicity and QoL after high-dose intensity-modulated radiotherapy (IMRT). Design, setting, and participants A total of 268 patients with localized prostate cancer were treated between 06/2004 and 12/2008 at a tertiary referral center. Median follow-up was 5 (range, 3–7.7) years. Intervention Patients underwent IMRT to a total dose of 86.4 Gy, 50% of patients underwent neoadjuvant and concurrent androgen-deprivation therapy. Outcome measurements and statistical analysis Patients were evaluated with the prospectively obtained International Prostate Symptom Score (IPSS) questionnaire. GU toxicity was also scored using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0; toxicity events were defined as increase over baseline. Differences in increases in IPSS sums and QoL index between baseline IPSS sum and QoL index groups were analyzed using the Kruskal-Wallis and Mann-Whitney tests. Univariate and multivariate Cox regression models were applied. Results and limitations The overall median IPSS sum increase during follow-up was 3, and was less pronounced among patients with severe compared with mild baseline symptoms (median increase 0 vs. 4; p < 0.0001). Overall, QoL index was unchanged after IMRT but appeared to improve in patients with dissatisfied baseline QoL compared with satisfied baseline QoL (p < 0.0001). Fifty-five (20%) and 2 (1%) patients developed grade 2 and 3 late GU toxicity; however, 28/57 (49%) of these resolved during follow-up. Even though the IPSS data was prospectively obtained, most patients were not treated within a prospective protocol. Conclusions Late GU toxicity after high-dose IMRT was mild and severe late GU toxicity was rare. Changes in IPSS sum and QoL index were dependent on the baseline

  14. (Radioiodinated free fatty acids)

    SciTech Connect

    Knapp, Jr., F. F.

    1987-12-11

    The traveler participated in the Second International Workshop on Radioiodinated Free Fatty Acids in Amsterdam, The Netherlands where he presented an invited paper describing the pioneering work at the Oak Ridge National Laboratory (ORNL) involving the design, development and testing of new radioiodinated methyl-branched fatty acids for evaluation of heart disease. He also chaired a technical session on the testing of new agents in various in vitro and in vivo systems. He also visited the Institute for Clinical and Experimental Nuclear Medicine in Bonn, West Germany, to review, discuss, plan and coordinate collaborative investigations with that institution. In addition, he visited the Cyclotron Research Center in Liege, Belgium, to discuss continuing collaborative studies with the Osmium-191/Iridium-191m radionuclide generator system, and to complete manuscripts and plan future studies.

  15. [High-dose intravenous immunoglobulin treatment].

    PubMed

    Taneichi, Hiromichi; Miyawaki, Toshio

    2011-03-01

    Intravenous immunoglobulin treatment was introduced as replacement therapy for patients with congenital agammaglobulinemia. For the last three decades, high-dose intravenous immunoglobulin (HD-IVIg) has been used for autoimmune diseases and systemic inflammatory diseases, such as idiopathic thrombocytopenic purpura, Kawasaki disease, myasthenia gravis and Guillain-Barré/syndrome. Although the immunomodulatory mechanisms of HD-IVIg remains unclear. Its use in many other diseases have been expected. Acute encephalitis/encephalopathy is a complex neurological syndrome associated with significant morbidity and mortality. The pathogenicity of brain dysfunction is still unknown. This review provides an overview and discussion of mechanisms that may be responsible for HD-IVIg effects in acute encephalitis/encephalopathy. PMID:21400848

  16. Randomized trial of high-dose interferon-alpha-2b combined with ribavirin in patients with chronic hepatitis C: Correlation between amino acid substitutions in the core/NS5A region and virological response to interferon therapy.

    PubMed

    Mori, Nami; Imamura, Michio; Kawakami, Yoshiiku; Saneto, Hiromi; Kawaoka, Tomokazu; Takaki, Shintaro; Aikata, Hiroshi; Takahashi, Shoichi; Chayama, Kazuaki

    2009-04-01

    The aim of this study was to compare the efficacy of high-dose interferon (IFN)-alpha-2b with standard dose of IFN-alpha-2b in combination with ribavirin (RBV) for patients with chronic hepatitis C virus (HCV) infection, and to investigate the predictive factors associated with virological response. Two hundred Japanese patients with high HCV viral load (>100 KIU/ml) were randomized to 6 or 10 mega units (MU) of 24-week IFN-alpha-2b with RBV. Predictive factors were investigated; including pretreatment amino acid (aa) sequences of the core region and the IFN-sensitive determining region (ISDR). The sustained virological response rate was not different in the two groups (24% vs. 30%) but the incidence of depression was significantly higher in the 10 MU group than 6 MU group (7% vs. 0%, P = 0.02). Younger age (<60) and HCV genotype (2a/b) were significant predictors of sustained virological response. In patients infected with genotype 1b, substitutions of core aa 70 and/or 91 were predictive for non-virological response (P < 0.001), and substitutions in the ISDR was observed frequently in virological responders. Early viral kinetics study showed that serum HCV core antigen decreased more slowly in both patients with aa 70 and/or 91 substitutions in the core and with absence of substitutions in the ISDR. In conclusion, the use of a higher dose of IFN-alpha-2b in combination with RBV did not improve virological response but resulted in higher incidence of depression. Amino acid substitutions in the core and ISDR are predictive of virological response to the therapy in patients with genotype 1b and high viral load. PMID:19235866

  17. Computed Tomography–Guided Interstitial High-Dose-Rate Brachytherapy in Combination With Regional Positive Lymph Node Intensity-Modulated Radiation Therapy in Locally Advanced Peripheral Non–Small Cell Lung Cancer: A Phase 1 Clinical Trial

    SciTech Connect

    Xiang, Li; Zhang, Jian-wen; Lin, Sheng; Luo, Hui-Qun; Wen, Qing-Lian; He, Li-Jia; Shang, Chang-Ling; Ren, Pei-Rong; Yang, Hong-Ru; Pang, Hao-Wen; Yang, Bo; He, Huai-Lin; Chen, Yue; Wu, Jing-Bo

    2015-08-01

    Purpose: To assess the technical safety, adverse events, and efficacy of computed tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy in combination with regional positive lymph node intensity modulated radiation therapy in patients with locally advanced peripheral non–small cell lung cancer (NSCLC). Methods and Materials: Twenty-six patients with histologically confirmed NSCLC were enrolled in a prospective, officially approved phase 1 trial. Primary tumors were treated with HDR brachytherapy. A single 30-Gy dose was delivered to the 90% isodose line of the gross lung tumor volume. A total dose of at least 70 Gy was administered to the 95% isodose line of the planning target volume of malignant lymph nodes using 6-MV X-rays. The patients received concurrent or sequential chemotherapy. We assessed treatment efficacy, adverse events, and radiation toxicity. Results: The median follow-up time was 28 months (range, 7-44 months). There were 3 cases of mild pneumothorax but no cases of hemothorax, dyspnea, or pyothorax after the procedure. Grade 3 or 4 acute hematologic toxicity was observed in 5 patients. During follow-up, mild fibrosis around the puncture point was observed on the CT scans of 2 patients, but both patients were asymptomatic. The overall response rates (complete and partial) for the primary mass and positive lymph nodes were 100% and 92.3%, respectively. The 1-year and 2-year overall survival (OS) rates were 90.9% and 67%, respectively, with a median OS of 22.5 months. Conclusion: Our findings suggest that HDR brachytherapy is safe and feasible for peripheral locally advanced NSCLC, justifying a phase 2 clinical trial.

  18. Radioiodine and thyroid disease: the beginning.

    PubMed

    Becker, D V; Sawin, C T

    1996-07-01

    In 1936, Karl Compton, then president of the Massachusetts Institute of Technology (MIT) and the thyroid group of the Massachusetts General Hospital (MGH), undertook a joint study that led to the production of small amounts of short-lived radioiodine (iodine 128, half-life, 25 min). The original intent was to use it for diagnosis and treatment of thyroid disease, but in order to explore the underlying physiology, their first work was performed in rabbits and published in 1938. It clearly showed that the radioiodine was selectively and avidly taken up by the thyroid gland. It was immediately apparent to the MGH-MIT group and another team working at the Berkeley, CA cyclotron that longer-lasting iodine isotopes were needed, and soon both developed procedures for cyclotron-produced 130 (half-life, 12.5 hr) and 131I (half-life, 8 d). In 1939, the Berkeley group, using 131I, was the first to show that the normal human thyroid gland accumulated radioiodine. By 1941, the MGH-MIT team, using mainly 130I, was able to successfully treat a few patients with hyperthyroidism, and so achieved their original goal. The Berkeley group did the same a few months later, using mainly 131I. Both presented results at the same meeting of the American Society for Clinical Investigation in Atlantic City, NJ in the spring of 1942. This was in the midst of World War II and it was not easy to get much 130I or 131I, so experience was limited. Although effective, radioiodine treatment of hyperthyroidism had not been widely adopted by the end of the war in 1945, partly because radioiodine remained in short supply and partly because another medical therapy for hyperthyroidism, antithyroid drugs, had been invented. However, by 1946, fission-derived radioiodine became readily available as a by-product of the Manhattan project in Oak Ridge, TN; hundreds of patients were treated within a few years, both for hyperthyroidism and for thyroid cancer. A new treatment, based on the physiological application

  19. The impurity of radioiodinated triolein

    PubMed Central

    Kennedy, J. A.; Kinloch, J. D.

    1964-01-01

    Commercially supplied radioiodinated triolein has been shown by thin-layer chromatography and silicic acid column chromatography to contain impurities, consisting mainly of diglycerides and monoglycerides, but also a small amount of free fatty acid. The effect of these impurities on the radioiodinated triolein absorption test requires further investigation. Images PMID:14149942

  20. [Treatment of multiple myeloma with high-dose chemotherapy and transplantation of autologous hematopoietic stem cells and subsequent maintenance therapy with interferon alfa-2b or interferon alfa 2b and dexamethasone. Report of the ongoing study of the "4W" Czech Myeloma Group].

    PubMed

    Adam, Z; Krejcí, M; Bacovský, J; Hejlová, N; Kuca, B; Svojgrová, M; Franková, H; Gumulec, J; Janca, J; Veprek, K; Januska, B; Lehanka, F; Rezek, Z; Praskac, P; Cahová, S; Vránová, M; Papajík, T; Králová, E; Novotná, J; Scudla, V; Koza, V; Drbal, J; Faber, E; Mareschová, I; Hájek, R

    1998-07-01

    We report our results with high-dose chemotherapy in previously untreated multiple myeloma patients (4 courses of VAD chemotherapy, collection of PBSC after priming with cyclophosphamide, 5 g/m2, high-dose chemotherapy with melphalan, 200 mg/m2). Second transplantation was indicated only for patients who did not achieve remission after the first high-dose therapy (paraprotein lower than 25% of the pretreatment value). For the second transplantation melphalan (200 mg/m2) with methylprednisolone (1.5 g for 5 days) were used as conditioning regimen. After high-dose therapy all patients were randomized into two arms of maintenance therapy: interferon alpha-2b or sequential maintenance therapy (interferon alpha-2b for 3 months followed after 4 week pause by 40 mg of dexamethasone days 1-4, 10-13 and 20-23. The administration of interferon alpha was resumed four weeks after the last dexamethasone for next three months. The maintenance therapy continued for 48 months or until the progression. Fifty-five patients were enrolled in the study from January 1996 to August 1997. Thirty-five patients have undergone the first transplantation and 57% of them reached complete remission. There were 10% of non-responders after the first high-dose regimen. The mean time to reach white blood cell count above 1 x 10(9)/L after the application of high dose melphalan and platelets more than 50 x 10(9)/L were 12.2 (range 6-16 days) and 12.4 (range 0-25 days), respectively. Grade 4 mucositis according to SWOG classification requiring total parenteral nutrition was presented in 40% of the patients. The mean number of 1 unit of platelets and 2 units of packed red blood cells transfusions were given within the posttransplant period. Early transplant related mortality was 3%. This paper describes the response and tolerance of each particular step of therapy. The follow-up has been too short to evaluate event-free and overall survivals. PMID:9748876

  1. Ocular toxicity following high dose chemotherapy and autologous transplant.

    PubMed

    Rubin, P; Hulette, C; Khawly, J A; Elkordy, M; Hussein, A; Vredenburgh, J J; Jaffe, G J; Peters, W P

    1996-07-01

    A 49-year-old woman received an autologous transplant for breast cancer. Six weeks later she noticed visual disturbance of the left eye which correlated with a visual field abnormality. There was a milder degree of visual disturbance in the right eye. Treatment with high-dose steroids partially stabilized the problem, which was felt to be an ischemic optic neuropathy. She ultimately died of respiratory failure. Pathology of the optic nerves revealed demyelination. Visual disturbances following high-dose chemotherapy are uncommon; the pathology to date has not been elucidated. Steroid therapy may be useful. PMID:8832031

  2. Cervical Gross Tumor Volume Dose Predicts Local Control Using Magnetic Resonance Imaging/Diffusion-Weighted Imaging—Guided High-Dose-Rate and Positron Emission Tomography/Computed Tomography—Guided Intensity Modulated Radiation Therapy

    SciTech Connect

    Dyk, Pawel; Jiang, Naomi; Sun, Baozhou; DeWees, Todd A.; Fowler, Kathryn J.; Narra, Vamsi; Garcia-Ramirez, Jose L.; Schwarz, Julie K.; Grigsby, Perry W.

    2014-11-15

    Purpose: Magnetic resonance imaging/diffusion weighted-imaging (MRI/DWI)-guided high-dose-rate (HDR) brachytherapy and {sup 18}F-fluorodeoxyglucose (FDG) — positron emission tomography/computed tomography (PET/CT)-guided intensity modulated radiation therapy (IMRT) for the definitive treatment of cervical cancer is a novel treatment technique. The purpose of this study was to report our analysis of dose-volume parameters predicting gross tumor volume (GTV) control. Methods and Materials: We analyzed the records of 134 patients with International Federation of Gynecology and Obstetrics stages IB1-IVB cervical cancer treated with combined MRI-guided HDR and IMRT from July 2009 to July 2011. IMRT was targeted to the metabolic tumor volume and lymph nodes by use of FDG-PET/CT simulation. The GTV for each HDR fraction was delineated by use of T2-weighted or apparent diffusion coefficient maps from diffusion-weighted sequences. The D100, D90, and Dmean delivered to the GTV from HDR and IMRT were summed to EQD2. Results: One hundred twenty-five patients received all irradiation treatment as planned, and 9 did not complete treatment. All 134 patients are included in this analysis. Treatment failure in the cervix occurred in 24 patients (18.0%). Patients with cervix failures had a lower D100, D90, and Dmean than those who did not experience failure in the cervix. The respective doses to the GTV were 41, 58, and 136 Gy for failures compared with 67, 99, and 236 Gy for those who did not experience failure (P<.001). Probit analysis estimated the minimum D100, D90, and Dmean doses required for ≥90% local control to be 69, 98, and 260 Gy (P<.001). Conclusions: Total dose delivered to the GTV from combined MRI-guided HDR and PET/CT-guided IMRT is highly correlated with local tumor control. The findings can be directly applied in the clinic for dose adaptation to maximize local control.

  3. High-dose thiamine as initial treatment for Parkinson's disease

    PubMed Central

    Costantini, Antonio; Pala, Maria Immacolata; Compagnoni, Laura; Colangeli, Marco

    2013-01-01

    Parkinson's disease (PD) is a systemic disease with motor and non-motor deficits. We recruited three patients with newly diagnosed PD. They were not under anti-Parkinson's therapy. Plasmatic thiamine was within healthy reference range. We performed the Unified Parkinson's Disease Rating Scale (UPDRS) and started a parenteral therapy with high doses of thiamine. The therapy led to a considerable improvement in the motor part of the UPDRS ranging from 31.3% to 77.3%. From this clinical observation, it is reasonable to infer that a focal, severe thiamine deficiency due to a dysfunction of thiamine metabolism could cause a selective neuronal damage in the centres that are typically hit in this disease. Injection of high doses of thiamine was effective in reversing the symptoms, suggesting that the abnormalities in thiamine-dependent processes could be overcome by diffusion-mediated transport at supranormal thiamine concentrations. PMID:23986125

  4. METASTATIC RADIOIODINE AVID STRUMA OVARII ASSOCIATED WITH PSEUDO-MEIGS' SYNDROME.

    PubMed

    Riaz, Saima; Bashir, Humayun; Hassan, Aamna; Syed, Aamir Ali; Hussain, Mudassar; Imtiaz, Saba

    2015-01-01

    We report a case of 21 years old lady who presented with ascites, left adnexal mass and elevated CA-125. With suspicion of ovarian malignancy, she underwent left salpingo-oophorectomy with omental biopsy. Histopathology revealed: 'follicular variant of papillary thyroid carcinoma arising in struma ovarii' with metastatic papillary thyroid carcinoma in omental and peritoneal nodules. Patient underwent total thyroidectomy followed by radioactive iodine therapy for metastatic omental and peritoneal disease. Post-therapy whole body scan, revealed extensive I-131 avid disease metastatic disease involving the chest, abdomen, pelvis and the musculoskeletal system. Patient was treated with multiple doses of high dose radioactive iodine. She became symptom free on supra-physiologic doses of oral thyroxin however her high thyroglobulin levels and residual radioiodine avid metastatic disease required further treatment. In literature a few cases of struma ovarii have been reported with elevated CA-125 and associated pseudo-Meigs' syndrome. The treatment for this rare disease is still not standardized and poses a therapeutic challenge. Our case emphasizes the need for a multidisciplinary approach for managing struma ovarii. PMID:26721055

  5. Novel radioiodinated neuroreceptor ligands

    SciTech Connect

    Musachio, J.L.

    1993-01-01

    Since many bioactive compounds do not readily undergo direct labeling with radioisotopes of iodine, the novel prosthetic groups, p-toluenesulfonate esters of (E)- and (Z)-3-(tri-n-butylstannyl)prop-2-en-1-ol, were designed to complement existing methods for radioiodine incorporation. The preparation and synthetic utility of these bifunctional reagents are described. These vinylstannylated alkylating agents were coupled with nucleophilic functionalities (amide nitrogen, secondary amine, tertiary alcohol) in acceptable to excellent yields. Regio- and stereospecific radioiododestannylation with retention of configuration occurred under mild, no-carrier-added conditions to give the corresponding radiolabeled N- or O-iodoallyl analogs in good radiochemical yields with high specific radioactivities. The methodology is versatile and well-suited to selective labeling of small molecules with radioisotopes of iodine. Of particular importance are the N-iodoallyl analogs of spiperone and the O-iodoallyl analog of diprenorphine for in vitro and in vivo studies of dopamine D[sub 2] and opioid receptors. For in vivo studies of central serotonin 5-HT[sub 2] receptors via single photon emission computed tomography (SPECT), novel radioiodinated N1-alkyl-2-iodo-LSD derivatives were synthesized. These target radioligands were prepared in moderate radiochemical yields. D-(+)-N1-ethyl-2-iodo-LSD, EIL, was identified as the most promising candidate of this series. [[sup 125]I]-EIL binds to central 5-HT[sub 2] receptors with high affinity and selectivity in vitro and labels 5-HT[sub 2] receptors in vivo with high specificity. For preparation of EIL labeled with [sup 123]I, an optimized procedure was developed that gave [[sup 123]I]-EIL in acceptable yields. This radioligand allowed visualization of serotonin 5-HT[sub 2] sites in living baboon brain via SPECT. [[sup 123]I]-EIL may serve as an agent for tomographic studies of human cerebral 5-HT[sub 2] receptors in normal and disease states.

  6. Prospective Evaluation of Subretinal Vessel Location in Polypoidal Choroidal Vasculopathy (PCV) and Response of Hemorrhagic and Exudative PCV to High-Dose Antiangiogenic Therapy (An American Ophthalmological Society Thesis)

    PubMed Central

    Kokame, Gregg T.

    2014-01-01

    Purpose: The purpose of this study was to determine the following: (1) Is polypoidal choroidal vasculopathy (PCV) a subretinal neovascular process, rather than a choroidal vascular anomaly? and (2) Is a higher dose of ranibizumab (2.0 mg/0.05 mL) more effective in treating PCV than the current dose (0.5 mg/0.05 mL) approved for treatment of age-related macular degeneration? Methods: Retrospective evaluation of PCV in 104 eyes of 86 patients was accomplished with use of indocyanine green angiography plus optical coherence tomography to localize the branching vascular network and the polyps. Nineteen eyes of 19 patients with active leaking and exudation underwent a prospective open-label trial of monthly high-dose intravitreal ranibizumab (2.0 mg/0.05 mL). The primary outcome was prevention of major vision loss (≤15 ETDRS letters). Secondary outcomes included adverse events, improved vision, and changes in subretinal hemorrhage, subretinal fluid, macular edema, and polypoidal complexes at 6 months. Results: The PCV vessels were localized beneath the retinal pigment epithelium (RPE) and above Bruch’s membrane in 103 (99%) of 104 eyes. In the high-dose ranibizumab trial at 6 months, none of the patients lost ≥15 letters in visual acuity, and 5 (26%) of 19 gained ≥15 letters. Decreases were noted in subretinal fluid in 14 (82%) of 17 eyes, subretinal hemorrhage in 12 (100%) of 12, RPE detachment in 14 (88%) of 16, macular edema in 11 (92%) of 12, and polyps in 15 (79%) of 19 eyes. Conclusions: PCV vessels are a subtype of subretinal neovascularization located above Bruch’s membrane and below RPE. High-dose ranibizumab (2.0 mg/0.05 mL) decreased exudation and hemorrhage and resulted in significant polyp regression, although branching vascular networks persisted. PMID:25646029

  7. An Unusual False-Positive Uptake of Radioiodine in Pericardial Effusion on Posttherapy Scan.

    PubMed

    Malhotra, Gaurav; Moghe, Surendra H; Ranade, Rohit; Asopa, R Ramesh V

    2016-07-01

    Posttherapy scan in a 21-year-old woman with papillary carcinoma of thyroid with lymph node metastasis, who received 5.55 GBq of radioiodine (I), revealed halo-like diffuse tracer uptake in the pericardial region. Echocardiography showed no abnormality except pericardial effusion, which subsided after reinstitution of levothyroxine therapy. Although rare, false-positive radioiodine uptake can occur in pericardial effusion secondary to thyroxine withdrawal-related hypothyroidism and needs close monitoring of the patient. PMID:27055143

  8. Post-radioiodine De Novo Onset Graves' Ophthalmopathy: Case Reports and a Review of the Literature.

    PubMed

    Batra, Ruchika; Krishnasamy, Senthil Kumar; Buch, Harit; Sandramouli, Soupramanien

    2015-05-01

    New-onset Graves' ophthalmopathy (GO) following radioiodine treatment (RAI) and worsening of existing GO are well-described in the endocrinology literature. These phenomena are recognized by ophthalmologists, yet poorly documented in the ophthalmology literature. Two male patients, aged 43 and 62 years, respectively, with Graves' disease without GO, received RAI. Four months later, one patient developed acute GO with unilateral reduction in visual acuity, conjunctival chemosis, lagophthalmos, bilateral severely restricted ocular motility, and lid retraction. High-dose intravenous steroids, followed by oral steroids, led to a dramatic clinical improvement. The second patient received a second dose of RAI for persistent hyperthyroidism and subsequently developed acute GO-comprising restricted ocular motility, peri-orbital swelling, and conjunctival chemosis. Symptoms gradually resolved on continued carbimazole treatment. Neither patient received pre-RAI prophylactic glucocorticoids, as currently they are only recommended for patients with pre-existing GO or multiple risk factors. We discuss the limitations of using this risk-based approach in preventing new-onset GO following RAI therapy. PMID:24409943

  9. Objective and Longitudinal Assessment of Dermatitis After Postoperative Accelerated Partial Breast Irradiation Using High-Dose-Rate Interstitial Brachytherapy in Patients With Breast Cancer Treated With Breast Conserving Therapy: Reduction of Moisture Deterioration by APBI

    SciTech Connect

    Tanaka, Eiichi; Yamazaki, Hideya; Yoshida, Ken; Takenaka, Tadashi; Masuda, Norikazu; Kotsuma, Tadayuki; Yoshioka, Yasuo; Inoue, Takehiro

    2011-11-15

    Purpose: To objectively evaluate the radiation dermatitis caused by accelerated partial breast irradiation (APBI) using high-dose-rate interstitial brachytherapy. Patients and Methods: The skin color and moisture changes were examined using a newly installed spectrophotometer and corneometer in 22 patients who had undergone APBI using open cavity implant high-dose-rate interstitial brachytherapy (36 Gy in six fractions) and compared with the corresponding values for 44 patients in an external beam radiotherapy (EBRT) control group (50-60 Gy in 25-30 fractions within 5-6 weeks) after breast conserving surgery. Results: All values changed significantly as a result of APBI. The extent of elevation in a Asterisk-Operator (reddish) and reduction in L Asterisk-Operator (black) values caused by APBI were similar to those for EBRT, with slightly delayed recovery for 6-12 months after treatment owing to the surgical procedure. In contrast, only APBI caused a change in the b Asterisk-Operator values, and EBRT did not, demonstrating that the reduction in b Asterisk-Operator values (yellowish) depends largely on the surgical procedure. The changes in moisture were less severe after APBI than after EBRT, and the recovery was more rapid. The toxicity assessment using the Common Toxicity Criteria, version 3, showed that all dermatitis caused by APBI was Grade 2 or less. Conclusion: An objective analysis can quantify the effects of APBI procedures on color and moisture cosmesis. The radiation dermatitis caused by APBI using the present schedule showed an equivalent effect on skin color and a less severe effect on moisture than the effects caused by standard EBRT.

  10. Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B Study 9222

    PubMed Central

    Moore, Joseph O.; George, Stephen L.; Dodge, Richard K.; Amrein, Philip C.; Powell, Bayard L.; Kolitz, Jonathan E.; Baer, Maria R.; Davey, Frederick R.; Bloomfield, Clara D.; Larson, Richard A.; Schiffer, Charles A.

    2005-01-01

    The Cancer and Leukemia Group B (CALGB) study 9222 tested the hypothesis that treatment intensification of acute myeloid leukemia (AML) in first remission with multiple chemotherapy agents is superior to high-dose cytarabine (HiDAC) alone. We enrolled 474 patients younger than 60 years old with untreated de novo AML. Daunorubicin and cytarabine resulted in complete remission (CR) in 342 patients (72%), and 309 of these patients were randomized to receive one of 2 different intensification regimens. The first regimen consisted of 3 courses of HiDAC. The second regimen consisted of one course of HiDAC, a second course with etoposide and cyclophosphamide, and a third course with diaziquone and mitoxantrone. After a median follow-up time of 8.3 years, the median survival for all randomized patients was 2.8 years (95% CI, 1.9-6.8 years). There was no difference in disease-free survival (DFS) between the 2 regimens (P = .66). The median DFS was 1.1 years (95% CI, 0.9-1.7 years) for patients receiving HiDAC and 1.0 year (95% CI, 0.9-1.3 years) for those receiving multiagent chemotherapy. Cytogenetics was the only pretreatment characteristic prognostic for DFS, but there was no evidence of a differential treatment effect within cytogenetic risk groups. Toxicity was greater with multiagent chemotherapy. These 2 postremission regimens produced similar outcomes. PMID:15572587

  11. [Radioiodine versus surgery in the treatment of Graves' hyperthyroidism].

    PubMed

    Jukić, Tomislav; Stanicić, Josip; Petric, Vlado; Kusić, Zvonko

    2010-01-01

    The most common etiologic cause of thyrotoxicosis in children and adults is autoimmune Graves' (Basedow's) disease. Antithyroid medications, surgery and radioactive iodine have been used in the treatment of Graves' hyperthyroidism for more than six decades. The use of antithyroid drugs is the most common therapeutic approach. However, long-term remission with antithyroid drugs can be expected in 20-50% of adults and 20-30% of children. The methods for definitive treatment of Graves' hyperthyroidism are iodine-131 (radioiodine) and surgery. Both treatment modalities have benefits and risks and the decision is made according to the age, patient preference and the presence of other co-morbidities, individual characteristics of patients and the availability of certain treatment modality. Radioiodine is simple, safe, effective and economic procedure for definitive treatment of Graves' hyperthyroidism. It is administered ambulatory and can be given to the patient in thyrotoxicosis. Due to many benefits, radioiodine is preferred in most of the adult patients with Graves' hyperthyroidism while only small proportion of patients is sent to surgery. Radioiodine is especially the treatment of choice in elderly patients and patients with heart disease. In these patients radioiodine is indicated immediately after reaching euthyroidism with antithyroid drugs. Surgery is mainly indicated in younger patients, in the case of patient preference or in special indications. Clear indications for surgical treatment of Graves' hyperthyroidism are: suspected or confirmed malignancy, coexisting pathology that demands surgical treatment, pregnancy and breastfeeding, large goiter (> 80 grams) or goiter with symptoms and signs of compression, severe toxic side effects of antithyroid medications, requirement for immediate control of disease, age younger than 5 years and active ophtalmopathy. The risk of surgical treatment is negatively correlated with the surgeon's experience and nowadays

  12. The use of SPECT-CT improves accuracy of post-radioiodine therapy imaging and changes the management strategy in a case of advanced follicular thyroid carcinoma.

    PubMed

    Wong, T H; Amir Hassan, S Z

    2015-12-01

    This is a case of follicular thyroid carcinoma with extensive lung, bone and brain metastases. Multi-modality treatments including total thyroidectomy, modified radical neck dissection, cranial radiotherapy and Iodine-131 (RAI) therapy were instituted. Post RAI therapy planar whole body scan showed RAI avid metastases in the skull, cervical spine, bilateral lungs and abdomen. With the use of SPECTCT imaging, rare adrenal metastasis and additional rib metastasis were identified. Besides, management strategy was altered due to detection of non-RAI avid brain and lung metastatic lesions. PMID:26988209

  13. High-Dose Intravenous Corticosteroids for Ocular Inflammatory Diseases

    PubMed Central

    Charkoudian, Leon D.; Ying, Gui-shuang; Pujari, Siddharth S.; Gangaputra, Sapna; Thorne, Jennifer E.; Foster, C. Stephen; Jabs, Douglas A.; Levy-Clarke, Grace A.; Nussenblatt, Robert B.; Rosenbaum, James T.; Suhler, Eric B.; Kempen, John H.

    2011-01-01

    Purpose To evaluate the effectiveness and risk of complications of high-dose intravenous pulsed corticosteroids for non-infectious ocular inflammatory diseases. Methods Retrospective cohort study. One hundred four eyes of seventy patients who received high-dose intravenous corticosteroids for treatment of active ocular inflammation were identified from five centers. The main outcome measures were control of inflammation and occurrence of ocular or systemic complications within one month after treatment. Results Within ≤1 month of starting treatment, 57% of eyes achieved complete control of inflammation (95% confidence interval (CI): 33-83%), improving to 82% when near-complete control was included (95% CI: 61-96%). Most eyes (85%; 95% CI: 70-95%) gained clinically significant improvement in anterior chamber inflammation. One patient developed a colon perforation during treatment. No other major complications were recorded. Conclusions Treatment of ocular inflammation with high-dose intravenous corticosteroids resulted in substantial clinical improvement for most cases within one month. Complications of therapy were infrequent. PMID:22409561

  14. Autophagy activity is associated with membranous sodium iodide symporter expression and clinical response to radioiodine therapy in non-medullary thyroid cancer.

    PubMed

    Plantinga, Theo S; Tesselaar, Marika H; Morreau, Hans; Corssmit, Eleonora P M; Willemsen, Brigith K; Kusters, Benno; van Engen-van Grunsven, A C H; Smit, Johannes W A; Netea-Maier, Romana T

    2016-07-01

    Although non-medullary thyroid cancer (NMTC) generally has a good prognosis, 30-40% of patients with distant metastases develop resistance to radioactive iodine (RAI) therapy due to tumor dedifferentiation. For these patients, treatment options are limited and prognosis is poor. In the present study, expression and activity of autophagy was assessed in large sets of normal, benign and malignant tissues and was correlated with pathology, SLC5A5/hNIS (solute carrier family 5 member 5) protein expression, and with clinical response to RAI ablation therapy in NMTC patients. Fluorescent immunostaining for the autophagy marker LC3 was performed on 100 benign and 80 malignant thyroid tissues. Semiquantitative scoring was generated for both diffuse LC3-I intensity and number of LC3-II-positive puncta and was correlated with SLC5A5 protein expression and clinical parameters. Degree of diffuse LC3-I intensity and number of LC3-II-positive puncta scoring were not discriminative for benign vs. malignant thyroid lesions. Interestingly, however, in NMTC patients significant associations were observed between diffuse LC3-I intensity and LC3-II-positive puncta scoring on the one hand and clinical response to RAI therapy on the other hand (odds ratio [OR] = 3.13, 95% confidence interval [CI] =1.91-5.12, P = 0.01; OR = 5.68, 95%CI = 3.02-10.05, P = 0.002, respectively). Mechanistically, the number of LC3-II-positive puncta correlated with membranous SLC5A5 expression (OR = 7.71, 95%CI = 4.15-11.75, P<0.001), number of RAI treatments required to reach remission (P = 0.014), cumulative RAI dose (P = 0.026) and with overall remission and recurrence rates (P = 0.031). In conclusion, autophagy activity strongly correlates with clinical response of NMTC patients to RAI therapy, potentially by its capacity to maintain tumor cell differentiation and to preserve functional iodide uptake. PMID:27105307

  15. Total rod ERG suppression with high dose compassionate Fenretinide usage.

    PubMed

    Marmor, Michael F; Jain, Atul; Moshfeghi, Darius

    2008-11-01

    Fenretinide is a synthetic retinoid that interferes with the attachment of retinol to retinol binding protein. It may inhibit accumulation of A2E and lipofuscin, and is proposed as therapy for Stargardt disease. It is currently used for cancer therapy, and mild depression of rod function and dark adaptation is a side effect at standard dosage. We studied two youngsters (aged between 12 and 13) receiving high doses as compassionate treatment for neuroblastoma: 800 mg daily for 1 out of every 3 weeks, for roughly 2 years. Goldmann-Weekers dark adaptometry, ISCEV standard ERG and mfERG were performed, and blood was analyzed for vitamin A. Neither child complained of night blindness or showed retinal fundus abnormalities. On initial exam, dark adaptation thresholds were elevated by 3 log units, and there were no detectable rod ERG responses. However, cone responses and mfERG were normal. Retesting one subject 3 months after stopping the drug revealed normal rod thresholds (slightly delayed) and low normal rod ERG responses. Serum vitamin A levels were normal from both subjects, but there is no record of whether the samples were drawn during cycles on or off drug. Our study demonstrates that high dose Fenretinide can suppress rod function quite completely, although serum vitamin A and rod function apparently return to normal or near normal levels rapidly once the drug is stopped. It is intriguing that cone function and access to vitamin A seems largely independent of Fenretinide effects on retinol availability. PMID:18523815

  16. Abnormal radioiodine uptake on post-therapy whole body scan and sodium/iodine symporter expression in a dermoid cyst of the ovary: report of a case and review of the literature.

    PubMed

    Campennì, Alfredo; Giovinazzo, Salvatore; Tuccari, Giovanni; Fogliani, Simone; Ruggeri, Rosaria M; Baldari, Sergio

    2015-08-01

    In patients affected by differentiated thyroid cancer, the whole-body scan (WBS) with 131-radioiodine, especially when performed after a therapeutic activity of 131I, represents a sensitive procedure for detecting thyroid remnant and/or metastatic disease. Nevertheless, a wide spectrum of potentially pitfalls has been reported. Herein we describe a 63-year-old woman affected by follicular thyroid cancer, who was accidentally found to have an abdominal mass at post-dose WBS (pWBS). pWBS showed abnormal radioiodine uptake in the upper mediastinum, consistent with lymph-node metastases, and a slight radioiodine uptake in an abdominal focal area. Computed tomography revealed an inhomogeneous mass in the pelvis, previously unrecognized. The lesion, surgically removed, was found to be a typical dermoid cyst of the ovary, without any evidence of thyroid tissue. By immunohistochemistry, a moderate expression of the sodium-iodine symporter (NIS) was demonstrated in the epithelial cells, suggesting a NIS-dependent uptake of radioiodine by the cyst. PMID:26331324

  17. Radioiodine Remnant Ablation: A Critical Review

    PubMed Central

    Bal, Chandra Sekhar; Padhy, Ajit Kumar

    2015-01-01

    Radioiodine remnant ablation (RRA) is considered a safe and effective method for eliminating residual thyroid tissue, as well as microscopic disease if at all present in thyroid bed following thyroidectomy. The rationale of RRA is that in the absence of thyroid tissue, serum thyroglobulin (Tg) measurement can be used as an excellent tumor marker. Other considerations are like the presence of significant remnant thyroid tissue makes detection and treatment of nodal or distant metastases difficult. Rarely, microscopic disease in the thyroid bed if not ablated, in the future, could be a source of anaplastic transformation. On the other hand, microscopic tumor emboli in distant sites could be the cause of distant metastasis too. The ablation of remnant tissue would in all probability eliminate these theoretical risks. It may be noted that all these are unproven contentious issues except postablation serum Tg estimation that could be a good tumor marker for detecting early biochemical recurrence in long-term follow-up strategy. Radioactive iodine is administered as a form of “adjuvant therapy” for remnant ablation. There have been several reports with regard to the administered dose for remnant ablation. The first report of a prospective randomized clinical trial was published from India by a prospective randomized study conducted at the All India Institute of Medical Sciences, New Delhi in the year 1996. The study reported that increasing the empirical 131I initial dose to more than 50 mCi results in plateauing of the dose-response curve and thus, conventional high-dose remnant ablation needs critical evaluation. Recently, two important studies were published: One from French group and the other from UK on a similar line. Interestingly, all three studies conducted in three different geographical regions of the world showed exactly similar conclusion. The new era of low-dose remnant ablation has taken a firm scientific footing across the continents. PMID:26420983

  18. Long-Term Results of Fixed High-Dose I-131 Treatment for Toxic Nodular Goiter: Higher Euthyroidism Rates in Geriatric Patients

    PubMed Central

    Aktaş, Gül Ege; Turoğlu, Halil Turgut; Erdil, Tanju Yusuf; İnanır, Sabahat; Dede, Fuat

    2015-01-01

    Objective: Geriatric patient population has special importance due to particular challenges. In addition to the increase in incidence of toxic nodular goiter (TNG) with age, it has a high incidence in the regions of low-medium iodine intake such as in our country. The aim of this study was to evaluate the overall outcome of high fixed dose radioiodine (RAI) therapy, and investigate the particular differences in the geriatric patient population. Methods: One hundred and three TNG patients treated with high dose I-131 (370-740 MBq) were retrospectively reviewed. The baseline characteristics; age, gender, scintigraphic patterns and thyroid function tests before and after treatment, as well as follow-up, duration of antithyroid drug (ATD) medication and achievement of euthyroid or hypothyroid state were evaluated. The patient population was divided into two groups as those=>65 years and those who were younger, in order to assess the effect of age. Results: Treatment success was 90% with single dose RAI therapy. Hyperthyroidism was treated in 7±7, 2 months after RAI administration. At the end of the first year, overall hypothyroidism rate was 30% and euthyroid state was achieved in 70% of patients. Age was found to be the only statistically significant variable effecting outcome. A higher ratio of euthyroidism was achieved in the geriatric patient population. Conclusion: High fixed dose I-131 treatment should be preferred in geriatric TNG patients in order to treat persistent hyperthyroidism rapidly. The result of this study suggests that high fixed dose RAI therapy is a successful modality in treating TNG, and high rates of euthyroidism can be achieved in geriatric patients.

  19. Lower-dose (6 mg Daily) versus High-dose (30 mg Daily) Oral Estradiol Therapy of Hormone-receptor-positive, Aromatase-inhibitor-resistant Advanced Breast Cancer: A Randomized Phase 2 Study

    PubMed Central

    Ellis, Matthew J.; Gao, Feng; Dehdashti, Farrokh; Jeffe, Donna B.; Marcom, P. Kelly; Carey, Lisa A.; Dickler, Maura N.; Silverman, Paula; Fleming, Gini F.; Kommareddy, Aruna; Jamalabadi-Majidi, Shohreh; Crowder, Robert; Siegel, Barry A

    2012-01-01

    Context Estrogen deprivation therapy with aromatase inhibitors (AI) has been hypothesized to paradoxically sensitize hormone-receptor-positive breast cancer tumor cells to low-dose estradiol therapy. Objective To determine if estradiol 6-mg daily is a viable endocrine therapy for postmenopausal women with advanced AI-resistant hormone-receptor-positive breast cancer. Design, Setting and Patients A randomized Phase 2 trial of 6-mg versus 30-mg oral estradiol daily opened in April 2004 and was closed to enrollment in February 2008 (NCT00324259). Eligible patients had metastatic breast cancer treated with an AI with at least 24 weeks progression-free survival, or relapse after two or more years of adjuvant AI. Patients at high risk of estradiol-related adverse events were excluded. Main Outcome Measures The primary endpoint was clinical benefit rate – CBR (response plus stable disease at 24 weeks). Secondary outcomes included toxicity, progression-free survival (PFS), time to treatment failure (TTF), quality of life (QOL) and the predictive properties of the FDG-PET metabolic flare reaction. Results 66 patients were enrolled. The grade 3+ adverse event rate on the 30-mg arm (11/32; 95% CI: 23%–47%) was higher than that in 6-mg arm (4/34; 95% CI: 5%–22%) (P=.03). CBRs were 28% (9/32; 95% CI: 18% – 41%) on the 30-mg arm and 29% (10/34; 95% CI: 19% – 42%) on the 6-mg arm. An estradiol44 stimulated increase in FDG uptake of ≥12% (prospectively defined) was predictive of response (positive predictive value of 80%; 95% CI: 61%–92%). Seven patients with estradiol-sensitive disease were retreated with AI upon estradiol progression, with two PR and one SD, suggesting resensitization to estrogen deprivation. Conclusions In women with advanced breast cancer and acquired resistance to AI, an estradiol dose of 6-mg daily provided a similar CBR as 30-mg daily, with fewer serious adverse events. The efficacy of treatment with the lower dose should be further examined

  20. Pre-therapeutic 124I PET(/CT) dosimetry confirms low average absorbed doses per administered 131I activity to the salivary glands in radioiodine therapy of differentiated thyroid cancer

    PubMed Central

    Hobbs, Robert F.; Stahl, Alexander; Knust, Jochen; Sgouros, George; Bockisch, Andreas

    2010-01-01

    Purpose Salivary gland impairment following high activity radioiodine therapy of differentiated thyroid cancer (DTC) is a severe side effect. Dosimetric calculations using planar gamma camera scintigraphy (GCS) with 131I and ultrasonography (US) provided evidence that the average organ dose per administered 131I activity (ODpA) is too low to account for observed radiation damages to the salivary glands. The objective of this work was to re-estimate the ODpA using 124I PET(/CT) as a more reliable approach than 131I GCS/US. Methods Ten DTC patients underwent a series of six (or seven) PET scans and one PET/CT scan after administration of ~23 MBq 124I-iodide. Volumes of interest (VOIs) drawn on the CT and serial PET images were used to determine the glandular volumes and the imaged 124I activities. To enable identical VOIs to be drawn on serial PET images, each PET was co-registered with the CT image. To correct for partial volume effect and for the artificial bias in the activity concentration due to cascading gamma coincidences occurring in 124I decay, the imaged activity was effectively corrected using isovolume recovery coefficients (RCs) based on recovery phantom measurements. A head-neck phantom, which contained 124I-filled spheres, was manufactured to validate the isovolume recovery correction method with a realistic patient-based phantom geometry and for a range of activity concentration regimes. The mean±standard deviation (range) ODpA projected for 131I was calculated using the absorbed dose fraction method. Results The ODpAs (in Gy/GBq) for the submandibular and parotid glands were 0.32±0.13 (0.18–0.55) and 0.31±0.10 (0.13–0.46), respectively. No significant differences (p>0.2) in the mean ODpA between 124I PET(/CT) and 131I GCS/US dosimetry was found. The validation experiment showed that the percentage deviations between RC-corrected and true activity concentrations were <10%. Conclusion 124I PET(/CT) dosimetry also corroborates the low ODpAs to

  1. Molecularly Targeted Therapy of Human Hepatocellular Carcinoma Xenografts with Radio-iodinated Anti-VEGFR2 Murine-Human Chimeric Fab

    PubMed Central

    Huang, Jianfei; Tang, Qi; Wang, Changjun; Yu, Huixin; Feng, Zhenqing; Zhu, Jin

    2015-01-01

    Vascular endothelial growth factor receptor 2 (VEGFR2) is traditionally regarded as an important therapeutic target in a wide variety of malignancies, such as hepatocellular carcinoma (HCC). We previously generated a murine-human anti-VEGFR2 chimeric Fab (cFab), named FA8H1, which has the potential to treat VEGFR2-overexpressing solid tumors. Here, we investigated whether FA8H1 can be used as a carrier in molecularly targeted therapy in HCC xenograft models. FA8H1 was labeled with 131I, and two HCC xenograft models were generated using BEL-7402 (high VEGFR2-expressing) and SMMC-7721 (low VEGFR2-expressing) cells, which were selected from five HCC cell lines. The biodistribution of 131I-FA8H1 was determined in both models by Single-Photon Emission Computed Tomography and therapeutic effects were monitored in nude mice bearing BEL-7402 xenografts. Finally, we determined the involvement of necrosis and apoptotic pathways in treated mice using immunohistochemistry. 131I-FA8H1 levels were dramatically reduced in blood and other viscera. The therapeutic effect of 131I-labeled FA8H1 in the BEL-7402 model was significantly better than that by 131I and FA8H1 alone. We observed extensive necrosis in the treated tumors, and both FasL and caspase 3 were up-regulated. Thus, 131I-anti-VEGFR2 cFab has the potential to be used for molecularly targeted treatment of HCC overexpressing VEGFR2. PMID:26021484

  2. High dose rate intraluminal irradiation in recurrent endobronchial carcinoma

    SciTech Connect

    Seagren, S.L.; Harrell, J.H.; Horn, R.A.

    1985-12-01

    Palliative therapy for previously irradiated patients with symptomatic recurrent endobronchial malignancy is a difficult problem. We have had the opportunity to treat 20 such patients with high dose rate (50-100 rad/min) endobronchial brachytherapy. Eligible patients had received previous high dose thoracic irradiation (TDF greater than or equal to 90), a performance status of greater than or equal to 50, and symptoms caused by a bronchoscopically defined and implantable lesion. The radiation is produced by a small cobalt-60 source (0.7 Ci) remotely afterloaded by cable control. The source is fed into a 4 mm diameter catheter which is placed with bronchoscopic guidance; it may oscillate if necessary to cover the lesion. A dose of 1,000 rad at 1 cm from the source is delivered. We have performed 22 procedures in 20 patients, four following YAG laser debulking. Most had cough, some with hemoptysis. Eight had dyspnea secondary to obstruction and three had obstructive pneumonitis. In 12, symptoms recurred with a mean time to recurrence of 4.3 months (range 1-9 months). Eighteen patients were followed-up and reexamined via bronchoscope 1-2.5 months following the procedure; two were lost to follow-up. All had at least 50 percent clearance of tumor, and six had complete clearance; most regressions were documented on film or videotape. In six, the palliation was durable. The procedure has been well tolerated with no toxicity. We conclude that palliative endobronchial high dose rate brachytherapy is a useful palliative modality in patients with recurrent endobronchial symptomatic carcinoma.

  3. Prognostic impact of progression to induction chemotherapy and prior paclitaxel therapy in patients with germ cell tumors receiving salvage high-dose chemotherapy in the last 10 years: a study of the European Society for Blood and Marrow Transplantation Solid Tumors Working Party.

    PubMed

    Necchi, A; Miceli, R; Bregni, M; Bokemeyer, C; Berger, L A; Oechsle, K; Schumacher, K; Kanfer, E; Bourhis, J H; Massard, C; Laszlo, D; Montoro, J; Flechon, A; Arpaci, F; Secondino, S; Wuchter, P; Dreger, P; Crysandt, M; Worel, N; Kruger, W; Ringhoffer, M; Unal, A; Nagler, A; Campos, A; Wahlin, A; Michieli, M; Sucak, G; Donnini, I; Schots, R; Ifrah, N; Badoglio, M; Martino, M; Raggi, D; Giannatempo, P; Rosti, G; Pedrazzoli, P; Lanza, F

    2016-03-01

    Little is known about the prognostic impact of prior paclitaxel therapy and response to induction chemotherapy defined as the regimen preceding high-dose chemotherapy (HDCT) for the salvage therapy of advanced germ cell tumors. Twenty European Society for Blood and Marrow Transplantation centers contributed data on patients treated between 2002 and 2012. Paclitaxel used in either prior lines of therapy or in induction-mobilization regimens was considered. Multivariable Cox analyses of prespecified factors were undertaken on PFS and overall survival (OS). As of October 2013, data for 324 patients had been contributed to this study. One hundred and ninety-two patients (59.3%) had received paclitaxel. Sixty-one patients (19%) had a progression to induction chemotherapy, 234 (72%) a response (29 (9%) missing or granulocyte colony-stimulating factor without chemotherapy). Both progression to induction chemotherapy and prior paclitaxel were significantly associated with shorter OS univariably (P<0.001 and P=0.032). On multivariable analysis from the model with fully available data (N=216) progression to induction was significantly prognostic for PFS and OS (P=0.003), but prior paclitaxel was not (P=0.674 and P=0.739). These results were confirmed after multiple imputation of missing data. Progression to induction chemotherapy could be demonstrated as an independent prognostic factor, in contrast to prior paclitaxel. PMID:26642334

  4. X-ray induced Sm{sup 3+} to Sm{sup 2+} conversion in fluorophosphate and fluoroaluminate glasses for the monitoring of high-doses in microbeam radiation therapy

    SciTech Connect

    Vahedi, Shahrzad; Okada, Go; Morrell, Brian; Muzar, Edward; Koughia, Cyril; Kasap, Safa; Edgar, Andy; Varoy, Chris; Belev, George; Wysokinski, Tomasz; Chapman, Dean

    2012-10-01

    Fluorophosphate and fluoroaluminate glasses doped with trivalent samarium were evaluated as sensors of x-ray radiation for microbeam radiation therapy at the Canadian Light Source using the conversion of trivalent Sm{sup 3+} to the divalent form Sm{sup 2+}. Both types of glasses show similar conversion rates and may be used as a linear sensor up to {approx}150 Gy and as a nonlinear sensor up to {approx}2400 Gy, where saturation is reached. Experiments with a multi-slit collimator show high spatial resolution of the conversion pattern; the pattern was acquired by a confocal fluorescence microscopy technique. The effects of previous x-ray exposure may be erased by annealing at temperatures exceeding the glass transition temperature T{sub g} while annealing at T{sub A} < T{sub g} enhances the Sm conversion. This enhancement is explained by a thermally stimulated relaxation of host glass ionic matrix surrounding x-ray induced Sm{sup 2+} ions. In addition, some of the Sm{sup 3+}-doped glasses were codoped with Eu{sup 2+}-ions but the results show that there is no marked improvement in the conversion efficiency by the introduction of Eu{sup 2+}.

  5. Rituximab plus gemcitabine and oxaliplatin in patients with refractory/relapsed diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association trial.

    PubMed

    Mounier, Nicolas; El Gnaoui, Taoufik; Tilly, Hervé; Canioni, Danièle; Sebban, Catherine; Casasnovas, René-Olivier; Delarue, Richard; Sonet, Anne; Beaussart, Pauline; Petrella, Tony; Castaigne, Sylvie; Bologna, Serge; Salles, Gilles; Rahmouni, Alain; Gaulard, Philippe; Haioun, Corinne

    2013-11-01

    A previous pilot study with rituximab, gemcitabine and oxaliplatin showed promising activity in patients with refractory/relapsed B-cell lymphoma. We, therefore, conducted a phase II study to determine whether these results could be reproduced in a multi-institutional setting. This phase II study included 49 patients with refractory (n=6) or relapsing (n=43) diffuse large B-cell lymphoma. The median age of the patients was 69 years. Prior treatment included rituximab in 31 (63%) and autologous transplantation in 17 (35%) patients. International Prognostic Index at enrollment was >2 in 34 patients (71%). The primary endpoint was overall response rate after four cycles of treatment. Patients were planned to receive eight cycles if they reached at least partial remission after four cycles. After four cycles 21 patients (44%) were in complete remission and 8 (17%) in partial remission, resulting in an overall response rate of 61%. Factors significantly affecting overall response rate were early (<1 year) progression/relapse (18% versus 54%; P=0.001) and prior exposure to rituximab (23% versus 65%; P=0.004). Five-year progression-free and overall survival rates were 12.8% and 13.9%, respectively. Rituximab, gemcitabine and oxaliplatin were well tolerated with grade 3-4 infectious episodes in 22% of the cycles. These results are the first confirmation from a multicenter study that rituximab, gemcitabine and oxaliplatin provide a consistent response rate in patients with refractory/relapsed diffuse large B-cell lymphoma. This therapy can now be considered as a platform for new combinations with targeted treatments. This trial was registered at clinicaltrial.gov under #NCT00169195. PMID:23753028

  6. Rituximab plus gemcitabine and oxaliplatin in patients with refractory/relapsed diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association trial

    PubMed Central

    Mounier, Nicolas; El Gnaoui, Taoufik; Tilly, Hervé; Canioni, Danièle; Sebban, Catherine; Casasnovas, René-Olivier; Delarue, Richard; Sonet, Anne; Beaussart, Pauline; Petrella, Tony; Castaigne, Sylvie; Bologna, Serge; Salles, Gilles; Rahmouni, Alain; Gaulard, Philippe; Haioun, Corinne

    2013-01-01

    A previous pilot study with rituximab, gemcitabine and oxaliplatin showed promising activity in patients with refractory/relapsed B-cell lymphoma. We, therefore, conducted a phase II study to determine whether these results could be reproduced in a multi-institutional setting. This phase II study included 49 patients with refractory (n=6) or relapsing (n=43) diffuse large B-cell lymphoma. The median age of the patients was 69 years. Prior treatment included rituximab in 31 (63%) and autologous transplantation in 17 (35%) patients. International Prognostic Index at enrollment was >2 in 34 patients (71%). The primary endpoint was overall response rate after four cycles of treatment. Patients were planned to receive eight cycles if they reached at least partial remission after four cycles. After four cycles 21 patients (44%) were in complete remission and 8 (17%) in partial remission, resulting in an overall response rate of 61%. Factors significantly affecting overall response rate were early (<1 year) progression/relapse (18% versus 54%; P=0.001) and prior exposure to rituximab (23% versus 65%; P=0.004). Five-year progression-free and overall survival rates were 12.8% and 13.9%, respectively. Rituximab, gemcitabine and oxaliplatin were well tolerated with grade 3–4 infectious episodes in 22% of the cycles. These results are the first confirmation from a multicenter study that rituximab, gemcitabine and oxaliplatin provide a consistent response rate in patients with refractory/relapsed diffuse large B-cell lymphoma. This therapy can now be considered as a platform for new combinations with targeted treatments. This trial was registered at clinicaltrial.gov under #NCT00169195. PMID:23753028

  7. [Clinical trials of ultra-high-dose methylcobalamin in ALS].

    PubMed

    Izumi, Yuishin; Kaji, Ryuji

    2007-10-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting both upper and lower motor neurons. Weakness may begin in the legs, hands, proximal arms, or pharynx. The course is relentless and progressive without remissions, relapses, or even stable plateaus. There is no effective drug therapy for ALS, although riluzole has been shown to prolong life in sufferers, without tracheostomy. A vitamin B12 analog, methylcobalamin, has a protective effect on cultured cortical neurons against glutamate-induced cytotoxicity. We have shown the ultra-high-dose methylcobalamin (25 mg/day i.m.) slows down the progressive reduction of the CMAP (compound muscle action potential) amplitudes in ALS in the short term (4 weeks). The latencies of SSR (sympathetic skin response) were shorter after treatment (50 mg/day i.v., 2 weeks). In the long-term effect of methylcobalamin (50 mg/day i.m., twice a week), the survival time (or the period to become respirator-bound) was significantly longer in the treated group than in the untreated. Larger-scale randomized double blind trial was started in Japan in order to evaluate the long-term efficacy and the safety of ultra-high-dose methylcobalamin for sporadic or familial cases of ALS. PMID:17969354

  8. High sensitive airborne radioiodine monitor.

    PubMed

    Ogata, Yoshimune; Yamasaki, Tadashi; Hanafusa, Ryuji

    2013-11-01

    Airborne radioiodine monitoring includes a problem in that commercial radioactive gas monitors have inadequate sensitivity. To solve this problem, we designed a highly sensitive monitoring system. The higher counting efficiency and lower background made it possible to perform the low-level monitoring. The characteristics of the system were investigated using gaseous (125)I. The minimum detectable activity concentration was 1 × 10(-4)Bq cm(-3) for 1 min counting, which is one tenth of the legal limit for the radiation controlled areas in Japan. PMID:23602709

  9. A Logical levothyroxine dose Individualization: Optimization Approach at discharge from Radioiodine therapy ward and during follow-up in patients of Differentiated Thyroid Carcinoma: Balancing the Risk based strategy and the practical issues and challenges: Experience and Views of a large volume referral centre in India

    PubMed Central

    Basu, Sandip; Abhyankar, Amit; Asopa, Ramesh; Chaukar, Devendra; DCruz, Anil K

    2013-01-01

    In this communication, the authors discuss the issue of individualization of thyrotropin suppressive therapy in differentiated thyroid carcinoma (DTC) patients and share their views with respect to optimizing the dose of levothyroxine (LT) prescription both during discharge from radioiodine therapy ward and during follow-up. The changing management paradigm at our Institute during post-thyroidectomy period and during the preparation for radioiodine scan is also briefly highlighted. Five factors can be identified as important determinants for the dose individualization approach: (1) Persistence or absence of metastatic disease, (2) the risk characteristics of the patient and the tumor (3) patient's clinical profile, symptomatology, and contraindications (4) the feasibility to ensure a proper thyroid stimulating hormone TSH suppression level (depends on patient's socio-economic and educational background, the connectivity with the local physician and his expertise) (5) time period elapsed since initial diagnosis. While discussing each individual case scenario, the authors, based upon their experience in one of the busiest thyroid cancer referral centers in the country, discuss certain unaddressed points in the current guideline recommendations, deviations made and some challenges toward employing them into practice, which could be situation and center specific. In addition to these, the value of clinical examination, patient profile and detailed enquiry about clinical symptomatology by the attending physician in each follow-up visit cannot be overemphasized. According to the authors, this aspect, quite important for dose determination in an individual, is relatively underrepresented in the present guidelines. It would also be worthwhile to follow a conservative approach (till clear data emerges) in patients who have characteristics of “high-risk” disease, but are clinically and biochemically disease free, if no medical contraindications exist and patient

  10. High-dose naloxone in tardive dyskinesia.

    PubMed

    Lindenmayer, J P; Gardner, E; Goldberg, E; Opler, L A; Kay, S R; van Praag, H M; Weiner, M; Zukin, S

    1988-10-01

    Tardive dyskinesia (TD) is thought to result from nigrostriatal dopaminergic supersensitivity secondary to prolonged neuroleptic exposure. Preclinical studies have demonstrated that the opiate antagonist naloxone can acutely reverse a haloperidol-induced hyperdopaminergic state. In a trial of high-dose naloxone, 20 patients with TD received i.v. naloxone (20 mg, 40 mg, and placebo) under double-blind conditions. At baseline and at regular postdrug intervals, patients were evaluated using a battery of motor, clinical, and neuropsychological measures to study effects on neurological, behavioral, and cognitive functions. There was a significant improvement in involuntary movements at 30 min postnaloxone, together with improvement in clinical ratings at that time point, as well as some cognitive changes. The implications of these findings for the putative functional relationship between dopaminergic and enkephalinergic systems in the nigrostriatal area are discussed. PMID:3070611

  11. High-dose thiamine improves the symptoms of fibromyalgia.

    PubMed

    Costantini, Antonio; Pala, Maria Immacolata; Tundo, Silvia; Matteucci, Pietro

    2013-01-01

    Living with fibromyalgia means living with chronic pain, fatigue, sleep disorders and other associated key symptoms. To date, pharmacotherapy generally produces modest benefits. Some observations indicate that the large majority of symptoms of fibromyalgia could be the clinical manifestation of a mild thiamine deficiency due to a dysfunction of the active transport of thiamine from the blood to the mitochondria or to enzymatic abnormalities. Between June and July 2011, we recruited three female patients affected by fibromyalgia. We proceeded with the study of the patients' history, a physical examination, an evaluation of chronic widespread pain using the Visual Numeric Scale and an evaluation of the fatigue using the Fatigue Severity Scale were also performed. The levels of thiamine and thiamine pyrophosphate in the blood were determined. After the therapy with high doses of thiamine, in the patients, there was an appreciable improvement of the symptoms. PMID:23696141

  12. High-dose thiamine improves the symptoms of Friedreich's ataxia

    PubMed Central

    Costantini, Antonio; Giorgi, Rafaela; D'Agostino, Sonia; Pala, Maria Immacolata

    2013-01-01

    Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder characterised by progressive gait and limb ataxia, dysarthria, areflexia, loss of position sense and a progressive motor weakness of central origin. Some observations indicate that all symptoms of FRDA ataxia could be the manifestation of a thiamine deficiency because of enzymatic abnormalities. Two patients with FRDA were under rehabilitative treatment from February 2012 to February 2013. The scale for assessment and rating of ataxia was performed. The patient began an intramuscular therapy with 100 mg of thiamine every 3–5  days. Injection of high-dose thiamine was effective in reversing the motor failure. From this clinical observation, it is reasonable to infer that a thiamine deficiency due to enzymatic abnormalities could cause a selective neuronal damage in the centres that are typically affected by this disease. PMID:23704441

  13. High dose thiamine improves fatigue in multiple sclerosis

    PubMed Central

    Costantini, Antonio; Nappo, Agostino; Pala, Maria Immacolata; Zappone, Antonietta

    2013-01-01

    The majority of the patients with multiple sclerosis (MS) experience fatigue. Some observations indicate that fatigue and related manifestations concomitant with MS could be associated with an intracellular mild thiamine deficiency. We recruited 15 patients with MS who also experience fatigue and assessed the severity of the fatigue using the Fatigue Severity Scale. Although blood thiamine and thiamine pyrophosphate levels were within normal limit in all the patients, high-dose thiamine therapy administered orally or parenterally led to an appreciable improvement of the fatigue. The absence of apparent decrease in blood thiamine despite the presence of symptoms referable to a mild thiamine deficiency suggests that these patients may have a dysfunction of the mechanisms of intracellular transport or structural enzymatic abnormalities. The administration of large quantities of thiamine was effective in reversing the fatigue in MS, suggesting that the abnormalities in thiamine-dependent processes could be overcome by diffusion-mediated transport at supranormal thiamine concentrations. PMID:23861280

  14. High-dose thiamine improves the symptoms of fibromyalgia

    PubMed Central

    Costantini, Antonio; Pala, Maria Immacolata; Tundo, Silvia; Matteucci, Pietro

    2013-01-01

    Living with fibromyalgia means living with chronic pain, fatigue, sleep disorders and other associated key symptoms. To date, pharmacotherapy generally produces modest benefits. Some observations indicate that the large majority of symptoms of fibromyalgia could be the clinical manifestation of a mild thiamine deficiency due to a dysfunction of the active transport of thiamine from the blood to the mitochondria or to enzymatic abnormalities. Between June and July 2011, we recruited three female patients affected by fibromyalgia. We proceeded with the study of the patients’ history, a physical examination, an evaluation of chronic widespread pain using the Visual Numeric Scale and an evaluation of the fatigue using the Fatigue Severity Scale were also performed. The levels of thiamine and thiamine pyrophosphate in the blood were determined. After the therapy with high doses of thiamine, in the patients, there was an appreciable improvement of the symptoms. PMID:23696141

  15. Modern trends and development in high-dose luminescent measurements

    NASA Astrophysics Data System (ADS)

    Kortov, V.

    2014-11-01

    Main application areas of high-dose dosimetry are described. The requirements to the materials for high-dose luminescent detectors are set. The examples of successful high-dose measurements using radiation-resistant phosphors are given. Viability of using materials with deep traps to detect intensive radiation flows is grounded. Characteristics of high-dose measurements using highly sensitive detectors TLD-500 (Al2O3:C) and LiF:Mg,Cu,P are discussed.

  16. Radioiodine in the Savannah River Site environment

    SciTech Connect

    Kantelo, M.V.; Bauer, L.R.; Marter, W.L.; Murphy, C.E. Jr.; Zeigler, C.C.

    1993-01-15

    Radioiodine, which is the collective term for all radioactive isotopes of the element iodine, is formed at the Savannah River Site (SRS) principally as a by-product of nuclear reactor operations. Part of the radioiodine is released to the environment during reactor and reprocessing operations at the site. The purpose of this report is to provide an introduction to radioiodine production and disposition, its status in the environment, and the radiation dose and health risks as a consequence of its release to the environment around the Savannah River Plant. A rigorous dose reconstruction study is to be completed by thee Center for Disease Control during the 1990s.

  17. Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer

    PubMed Central

    2016-01-01

    Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term “theranostics” was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging. PMID:27239470

  18. Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer.

    PubMed

    Ahn, Byeong-Cheol

    2016-01-01

    Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term "theranostics" was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging. PMID:27239470

  19. Administration of high-dose interleukin-2 in a 2-year-old with metastatic melanoma.

    PubMed

    Bernhardt, M Brooke; Hicks, M John; Pappo, Alberto S

    2009-12-15

    Malignant melanoma is rare in pediatrics, and therapies for patients with disseminated disease have not been well studied. This report describes our experience with the use of high-dose interleukin 2 (aldesleukin, IL-2) in a 2-year-old child with metastatic melanoma and describes our approach for the administration of this agent to young patients. PMID:19731326

  20. Ketobemidone may alter busulfan pharmacokinetics during high-dose therapy.

    PubMed

    Hassan, M; Svensson, J O; Nilsson, C; Hentschke, P; Al-Shurbaji, A; Aschan, J; Ljungman, P; Ringdén, O

    2000-08-01

    The authors report a possible interaction between ketobemidone and busulfan during myeloablative treatment of a patient with acute myeloid leukemia. At the time of admission, the patient was receiving ketobemidone 1,000 mg/d as analgesic for a rectal fissure. The patient started conditioning prior to bone marrow transplantation with busulfan (1 mg/kg x 4 for 4 days). High busulfan plasma concentrations were observed after the first dose and the next doses were reduced to 0.7 mg/kg. The kinetics of both drugs revealed that an increase in ketobemidone concentration was followed by an increase in busulfan levels. Substituting ketobemidone with morphine resulted in a decrease in busulfan concentration despite increasing the dose once more to 1 mg/kg. PMID:10942175

  1. No Salvage Using High-Dose Chemotherapy Plus/Minus Reirradiation for Relapsing Previously Irradiated Medulloblastoma

    SciTech Connect

    Massimino, Maura Gandola, Lorenza; Spreafico, Filippo; Biassoni, Veronica; Luksch, Roberto; Collini, Paola; Solero, Carlo N.; Simonetti, Fabio; Pignoli, Emanuele; Cefalo, Graziella; Poggi, Geraldina; Modena, Piergiorgio Ph.D.; Mariani, Luigi; Potepan, Paolo; Podda, Marta; Casanova, Michela; Pecori, Emilia; Acerno, Stefania; Ferrari, Andrea; Terenziani, Monica

    2009-04-01

    Purpose: Myeloablative regimens were frequently used for medulloblastoma relapsing after craniospinal irradiation (CSI): in 1997-2002, we used repeated surgery, standard-dose and myeloablative chemotherapy, and reirradiation. Methods and Materials: In 10 patients, reinduction included sequential high-dose etoposide, high-dose cyclophosphamide/vincristine, and high-dose carboplatin/vincristine, then two myeloablative courses with high-dose thiotepa ({+-} carboplatin); 6 other patients received two of four courses of cisplatin/etoposide. Hematopoietic precursor mobilization followed high-dose etoposide or high-dose cyclophosphamide or cisplatin/etoposide therapy. After the overall chemotherapy program, reirradiation was prescribed when possible. Results: Seventeen patients were treated: previous treatment included CSI of 19.5-36 Gy with posterior fossa/tumor boost and chemotherapy in 16 patients. Fifteen patients were in their first and 2 in their second and third relapses, respectively. First progression-free survival had lasted a median of 26 months. Relapse sites included leptomeninges in 9 patients, spine in 4 patients, posterior fossa in 3 patients, and brain in 1 patient. Three patients underwent complete resection of recurrence, and 10 underwent reirradiation. Twelve of 14 patients with assessable tumor had an objective response after reinduction; 2 experienced progression and were not given the myeloablative courses. Remission lasted a median of 16 months. Additional relapses appeared in 13 patients continuing the treatment. Fifteen patients died of progression and 1 died of pneumonia 13 months after relapse. The only survivor at 93 months had a single spinal metastasis that was excised and irradiated. Survival for the series as a whole was 11-93 months, with a median of 41 months. Conclusions: Despite responses being obtained and ample use of surgery and reirradiation, second-line therapy with myeloablative schedules was not curative, barring a few

  2. High dose intravenous ciprofloxacin in febrile neutropenic patients.

    PubMed

    Johnson, P R; Yin, J A; Tooth, J A

    1990-12-01

    We have evaluated the use of high-dose intravenous ciprofloxacin as monotherapy in the empirical therapy of febrile episodes in neutropenic patients during the course of a randomized trial comparing ciprofloxacin with a standard combination regimen. Sixty-four episodes of fever were studied in a high risk population of 42 patients mostly undergoing intensive chemotherapy for leukaemia. Ciprofloxacin achieved clinical responses as follows: completely successful in 39%, partially successful in 20%, and unsuccessful in 41%. Infections were microbiologically documented in 37 (58%), with Gram-positive bacteria (of which 37% were coagulase negative staphylococci and 34% were streptococci) accounting for 81% of all organisms cultured. Responses in documented infections were as follows; completely successful in 32%, partially successful in 27%, and unsuccessful in 41%. One infection-related death occurred 30 h after starting ciprofloxacin, and a further three patients died before the resolution of neutropenia. The early death was caused by fulminant infection with a ciprofloxacin-resistant Pseudomonas aeruginosa. No other ciprofloxacin resistance was seen amongst eight Gram-negative isolates. There was no evidence of emerging ciprofloxacin resistance during the course of the study. Ciprofloxacin was associated with a low incidence of adverse events with skin rash (five cases) and nausea (one case) being reported as possibly or probably related to ciprofloxacin. We conclude that high-dose intravenous ciprofloxacin may be safely employed as monotherapy in the empirical treatment of febrile episodes in neutropenic patients. It has the additional advantages of twice daily administration, the availability of intravenous and oral presentations, and absence of cross-allergy in beta-lactam antibiotic hypersensitive patients. PMID:2292537

  3. Radiation Therapy

    MedlinePlus

    Radiation therapy is a cancer treatment. It uses high doses of radiation to kill cancer cells and stop them ... places inside your body. The type of radiation therapy you receive depends on many factors, including The ...

  4. Radioactive Iodine (I-131) Therapy for Hyperthyroidism

    MedlinePlus

    ... Iodine (I-131) Therapy Radioiodine therapy is a nuclear medicine treatment for an overactive thyroid, a condition ... locally overactive in producing too much thyroid hormone. Nuclear medicine is a branch of medical imaging that ...

  5. Radioiodine thyroid ablation in graves' hyperthyroidism: merits and pitfalls.

    PubMed

    Nwatsock, J F; Taieb, D; Tessonnier, L; Mancini, J; Dong-A-Zok, F; Mundler, O

    2012-01-01

    Ablative approaches using radioiodine are increasingly proposed for the treatment of Graves' disease (GD) but their ophthalmologic and biological autoimmune responses remain controversial and data concerning clinical and biochemical outcomes are limited. The aim of this study was to evaluate thyroid function, TSH-receptor antibodies (TRAb) and Graves' ophthalmopathy (GO) occurrence after radioiodine thyroid ablation in GD. We reviewed 162 patients treated for GD by iodine-131 ((131)I) with doses ranging from 370 to 740 MBq, adjusted to thyroid uptake and sex, over a 6-year period in a tertiary referral center. Collected data were compared for outcomes, including effectiveness of radioiodine therapy (RIT) as primary endpoint, evolution of TRAb, and occurrence of GO as secondary endpoints. The success rate was 88.3% within the first 6 months after the treatment. The RIT failure was increased in the presence of goiter (adjusted odds ratio = 4.1, 95% confidence interval 1.4-12.0, P = 0.010). The TRAb values regressed with time (r = -0.147; P = 0.042) and patients with a favorable outcome had a lower TRAb value (6.5 ± 16.4 U/L) than those with treatment failure (23.7 ± 24.2 U/L, P < 0.001). At the final status, 48.1% of patients achieved normalization of serum TRAb. GO occurred for the first time in 5 patients (3.7%) who were successfully cured for hyperthyroidism but developed early and prolonged period of hypothyroidism in the context of antithyroid drugs (ATD) intolerance (P = 0.003) and high TRAb level (P = 0.012). On the basis the results of this study we conclude that ablative RIT is effective in eradicating Graves' hyperthyroidism but may be accompanied by GO occurrence, particularly in patients with early hypothyroidism and high pretreatment TRAb and/or ATD intolerance. In these patients, we recommend an early introduction of LT4 to reduce the duration and the degree of the radioiodine-induced hypothyroidism. PMID:22942775

  6. Benefits of automated surface decontamination of a radioiodine ward.

    PubMed

    Westcott, Eliza; Broadhurst, Alicia; Crossley, Steven; Lee, Lloyd; Phan, Xuyen; Scharli, Rainer; Xu, Yan

    2012-02-01

    A floor-washing robot has been acquired to assist physicists with decontamination of radioiodine therapy ward rooms after discharge of the patient at Sir Charles Gairdner Hospital. The effectiveness of the robot in decontaminating the ward has been evaluated. A controlled experiment was performed by deliberately contaminating a polyvinyl chloride flooring offcut with 131I followed by automated decontamination with the robot. The extent of fixed and removable contamination was assessed before and after decontamination by two methods: (1) direct Geiger-Mueller counting and (2) beta-counting wipe tests. Surface contamination was also assessed in situ on the ward by Geiger-Mueller counting and wipe testing. Contamination maps confirmed that contamination was removed rather than spread around by the robot. Wipe testing revealed that the robot was successful in clearing approximately 60-80% of removable contamination. The robotic floor-washing device was considered suitable to provide effective automated decontamination of the radioiodine ward. In addition, the robot affords other benefits: the time spent by the physicists decontaminating the room is greatly reduced offering financial and occupational safety and health benefits. The robot has also found utility in other decontamination applications in the healthcare environment. PMID:22249471

  7. DMSO Increases Radioiodination Yield of Radiopharmaceuticals

    PubMed Central

    Wang, Ketai; Adelstein, S. James; Kassis, Amin I.

    2007-01-01

    A high-yield radioiodination method for various types of molecules is described. The approach employs DMSO as precursor solvent, a reaction ratio of 2–5 precursor molecules per iodine atom, 5–10 μg oxidant, and a 10–25-μl reaction volume. The solution is vortexed at room temperature for 1–5 min and progress of the reaction is assessed by HPLC. Radioiodinated products are obtained in ≥95% yield and meet the requirements for radiotracer imaging, biodistribution studies, and molecular and cellular biology research. PMID:17931872

  8. Mammary radioiodine accumulation due to functional sodium iodide symporter expression in a benign fibroadenoma

    SciTech Connect

    Berger, F.; Unterholzner, S.; Diebold, J.; Knesewitsch, P.; Hahn, K.; Spitzweg, C. . E-mail: Christine.Spitzweg@med.uni-muenchen.de

    2006-11-03

    The sodium iodide symporter (NIS) has been characterized to mediate the active transport of iodide not only in the thyroid gland but also in various non-thyroidal tissues, including lactating mammary gland and the majority of breast cancers, thereby offering the possibility of diagnostic and therapeutic radioiodine application in breast cancer. In this report, we present a 57-year-old patient with multifocal papillary thyroid carcinoma, who showed focal radioiodine accumulation in a lesion in the right breast on a posttherapy {sup 131}I scan following radioiodine therapy. CT and MR-mammography showed a focal solid lesion in the right breast suggestive of a fibroadenoma, which was confirmed by histological examination. Immunostaining of paraffin-embedded tumor tissue sections using a human NIS antibody demonstrated NIS-specific immunoreactivity confined to epithelial cells of mammary ducts. In conclusion, in a thyroid cancer patient we identified a benign fibroadenoma of the breast expressing high levels of functionally active NIS protein as underlying cause of focal mammary radioiodine accumulation on a posttherapy {sup 131}I scan. These data show for the first time that functional NIS expression is not restricted to lactating mammary gland and malignant breast tissue, but can also be detected in benign breast lesions, such as fibroadenomata of the breast.

  9. Response of osteosarcoma to preoperative intravenous high-dose methotrexate chemotherapy: CT evaluation

    SciTech Connect

    Mail, J.T.; Cohen, M.D.; Mirkin, L.D.; Provisor, A.J.

    1985-01-01

    The histologic response of an osteosarcoma to preamputation high-dose methotrexate therapy can be used to determine the optimum maintenance chemotherapy regimen to be administered after amputation. This study evaluates computed tomography (CT) as a method of assessing the response of the tumor to the methotrexate therapy. Nine patients with nonmetastatic osteosarcoma of an extremity had a CT scan of the tumor at initial presentation. This was compared with a second CT scan after four courses of high-dose intravenous methotrexate. Each set of scans was evaluated for changes in bony destruction, soft-tissue mass, pattern of calcification, and extent of tumor involvement of the marrow cavity. These findings were correlated with the histologic response of the tumor as measured by the degree of tumor necrosis. The changes seen on CT correlated well with the degree of the histologic response in seven of the nine patients.

  10. Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions.

    PubMed Central

    Naderer, O; Nafziger, A N; Bertino, J S

    1997-01-01

    The effects of a 10-day course of moderate-dose (10 mg/kg/day) or high-dose (20 mg/kg/day) trimethoprim therapy on serum creatinine, measured creatinine clearance, urinary creatinine excretion, and serum folate were studied in 20 healthy volunteers. Serum creatinine concentrations increased significantly during trimethoprim therapy, began to decrease near day 10, and returned to baseline during the washout phase at both dosage levels. At the same time, measured creatinine clearance and urine creatinine changed in the opposite direction. No clinical or statistical differences were noted between changes in the moderate- versus the high-dose phases. Serum folate concentration decreases during high-dose trimethoprim therapy were statistically significant. Adverse drug reactions in the two groups were statistically different during the first study period, with the high-dose group having a 75% incidence rate and the moderate-dose group having an 11% incidence rate (P < 0.02). Serum creatinine, measured creatinine clearance, and urinary creatinine excretion demonstrated statistically, but not clinically, significant changes during trimethoprim therapy. In addition, high-dose trimethoprim caused significantly more adverse drug reactions than moderate-dose trimethoprim in normal volunteers. PMID:9371351