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Sample records for sequential high-dose chemotherapy

  1. High-dose treatment with autologous stem cell transplantation versus sequential chemotherapy: the GELA experience.

    Science.gov (United States)

    Bosly, A; Haioun, C; Gisselbrecht, C; Reyes, F; Coiffier, B

    2001-07-01

    Autologous stem-cell transplantation (ASCT) has permitted to deliver high-dose therapy (HDT). In aggressive lymphomas, the GELA group conducted prospective and retrospective studies comparing HDT + ASCT to conventional sequential chemotherapy. In relapsing patients and in partial remission, retrospective studies showed a survival advantage for HDT + ASCT over sequential chemotherapy. In complete response, advantage for HDT + ASCT was demonstrated in a prospective trial only for patients with high intermediate or high risk in the IPI score. The attainment of a maximal reduction of the tumoral mass before going HDT is very important either in first line or in relapsing patients.

  2. Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas.

    Science.gov (United States)

    Cortelazzo, Sergio; Tarella, Corrado; Gianni, Alessandro Massimo; Ladetto, Marco; Barbui, Anna Maria; Rossi, Andrea; Gritti, Giuseppe; Corradini, Paolo; Di Nicola, Massimo; Patti, Caterina; Mulé, Antonino; Zanni, Manuela; Zoli, Valerio; Billio, Atto; Piccin, Andrea; Negri, Giovanni; Castellino, Claudia; Di Raimondo, Francesco; Ferreri, Andrés J M; Benedetti, Fabio; La Nasa, Giorgio; Gini, Guido; Trentin, Livio; Frezzato, Maurizio; Flenghi, Leonardo; Falorio, Simona; Chilosi, Marco; Bruna, Riccardo; Tabanelli, Valentina; Pileri, Stefano; Masciulli, Arianna; Delaini, Federica; Boschini, Cristina; Rambaldi, Alessandro

    2016-11-20

    Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis. Results Clinical response (complete response, 78% v 76%; partial response, 5% v 9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2% v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% ( P = .83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = .12), or overall survival (74% v 77%, respectively; P = .64). Significantly higher hematologic toxicity ( P < .001) and more infectious complications ( P < .001) were observed in the R-HDS arm. Conclusion In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.

  3. Pharmacogenetics and Pharmacokinetics in high-dose alkylating chemotherapy

    NARCIS (Netherlands)

    Ekhart, G.C. (Corine)

    2008-01-01

    High-dose chemotherapy in combination with peripheral blood progenitor cell transplantation has been developed as a possible curative treatment modality in several solid tumours. A frequently used high-dose regimen in the Netherlands is the CTC regimen, which is a 4-day course of cyclophosphamide,

  4. "Time sequential high dose of Cytarabine in acute myelocytic leukemia "

    Directory of Open Access Journals (Sweden)

    Ghavamzadeh A

    2003-05-01

    Full Text Available Given preliminary evidence of timed, sequential chemotherapy of high dose cytosine arabinoside the current study was initiated to assess the side effects and efficacy of this regimen in patients with newly acute myelocytic leukemia (AML. Nineteen adults who referred to Hematology-Oncology and Bone Marrow Transplantation (BMT research center of Tehran University of Medical Sciences were enrolled in a trial from Aug 1999 to Nov 2000. All patients had a Karnofski classification above 60%. At this time induction therapy consisted of daunorubicin or idarubicin given at a dose of 60 mg/m² and 12 mg/m² IV respectively on days 1-3, and cytarabine (Ara-C 100 mg/m² intravenously by continuous infusion on days 1-7, followed by Ara-C 1000 mg/m² given on day 8-10 every 12 hours by IV infusion. Consolidation therapy started after 35th day. Of 19 fully evaluable patients, 10 patients achieved a complete remission, whereas 36.6% patients succumbed to death due to regeneration failure. The clinical data show that the overall survival rate from diagnosis 55.5% (95% CI, 30.8-78.5 at 6 months for the entire cohort of the patients. Disease free survival is also 50% (95% CI, 26-74. Mean duration of death due to treatment was 20 days (range 17-29 after beginning the regimen. Presenting WBC counts, French-American-British (FAB classification, sex and age were not useful prognostic variables. Fever, diarrhea, nausea and vomiting and GI hemorrhage were seen in 19, 6, 4, 7 patients respectively. It seems the 3+7+3 regimen is a promising approach for the AML patients regarding to high complete remission rate, but more supportive care should be considered. Furthermore any, benefit in long-term outcome can’t be determined regardless to the choice of post remission therapy (e.g., GCSF, appropriate antibiotics and etc.

  5. Relevance of high-dose chemotherapy in solid tumours

    NARCIS (Netherlands)

    Nieboer, P; de Vries, EGE; Mulder, NH; van der Graaf, WTA

    Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with

  6. Unusual complication and successful high-dose chemotherapy ...

    African Journals Online (AJOL)

    ... treated with high-dose chemotherapy in our institution, complicated by unusual bilateral renal vein tumour thrombi and tumour lysis syndrome. We believe this unique case highlights the need for early recognition of current and potential complications on staging computed tomography imaging, as well as successful use of ...

  7. Radiotherapy and high-dose chemotherapy in advanced Ewing's tumors

    International Nuclear Information System (INIS)

    Pape, H.; Glag, M.; Gripp, S.; Wittkamp, M.; Schmitt, G.; Laws, H.J.; Kaik, B. van; Goebel, U.; Burdach, S.; Juergens, H.

    1999-01-01

    Background: Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early ( [de

  8. Conventional-Dose versus High-Dose Chemotherapy for Relapsed Germ Cell Tumors

    Directory of Open Access Journals (Sweden)

    Deaglan J. McHugh

    2018-01-01

    Full Text Available The majority of metastatic germ cell tumors (GCTs are cured with cisplatin-based chemotherapy, but 20–30% of patients will relapse after first-line chemotherapy and require additional salvage strategies. The two major salvage approaches in this scenario are high-dose chemotherapy (HDCT with autologous stem cell transplant (ASCT or conventional-dose chemotherapy (CDCT. Both CDCT and HDCT have curative potential in the management of relapsed/refractory GCT. However, due to a lack of conclusive randomized trials, it remains unknown whether sequential HDCT or CDCT represents the optimal initial salvage approach, with practice varying between tertiary institutions. This represents the most pressing question remaining for defining GCT treatment standards and optimizing outcomes. The authors review prognostic factors in the initial salvage setting as well as the major studies assessing the efficacy of CDCT, HDCT, or both, describing the strengths and weaknesses that formed the rationale behind the ongoing international phase III “TIGER” trial.

  9. Acute renal failure in high dose carboplatin chemotherapy

    NARCIS (Netherlands)

    Frenkel, J.; Kool, G.; de Kraker, J.

    1995-01-01

    Carboplatin has been reported to cause acute renal failure when administered in high doses to adult patients. We report a 4 1/2-year-old girl who was treated with high-dose carboplatin for metastatic parameningeal embryonal rhabdomyosarcoma. Acute renal failure developed followed by a slow partial

  10. The clinical pharmacology of alkylating agents in high-dose chemotherapy

    NARCIS (Netherlands)

    Huitema, A. D.; Smits, K. D.; Mathôt, R. A.; Schellens, J. H.; Rodenhuis, S.; Beijnen, J. H.

    2000-01-01

    Alkylating agents are widely used in high-dose chemotherapy regimens in combination with hematological support. Knowledge about the pharmacokinetics and pharmacodynamics of these agents administered in high doses is critical for the safe and efficient use of these regimens. The aim of this review is

  11. Severe encephalopathy after high-dose chemotherapy with autologous stem cell support for brain tumours

    NARCIS (Netherlands)

    van den Berkmortel, F.; Gidding, C.; de Kanter, M.; Punt, C. J. A.

    2006-01-01

    Recurrent medulloblastoma carries a poor prognosis. Long-term survival has been obtained with high-dose chemotherapy with autologous stem cell transplantation and secondary irradiation. A 21-year-old woman with recurrent medulloblastoma after previous chemotherapy and radiotherapy is presented. The

  12. Hemolytic uremic syndrome after high dose chemotherapy with autologous stem cell support

    NARCIS (Netherlands)

    van der Lelie, H.; Baars, J. W.; Rodenhuis, S.; Van Dijk, M. A.; de Glas-Vos, C. W.; Thomas, B. L.; van Oers, R. H.; von dem Borne, A. E.

    1995-01-01

    BACKGROUND: Chemotherapy intensification may lead to new forms of toxicity such as hemolytic uremic syndrome. METHODS: Three patients are described who developed this complication 4 to 6 months after high dose chemotherapy followed by autologous stem cell support. The literature on this subject is

  13. Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer

    NARCIS (Netherlands)

    Rodenhuis, S.; Bontenbal, M.; Hoesel, Q.G.C.M. van; Smit, W.M.; Nooij, M.A.; Voest, E.E.; Wall, E. van der; Hupperets, P.; Tinteren, H. van; Peterse, J.L.; Vijver, M.J. van de; Vries, E.G.E. de

    2006-01-01

    Background: High-dose chemotherapy in the adjuvant treatment of breast cancer has been abandoned by many. Patients and methods: 885 patients with stage III primary breast cancer and four or more axillary lymph node metastases were randomised to receive either five courses of FEC (fluorouracil,

  14. Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer

    NARCIS (Netherlands)

    Rodenhuis, S; Bontenbal, M; van Hoesel, QGCM; Smit, WM; Nooij, MA; Voest, EE; van der Wall, E; Hupperets, P; van Tinteren, H; Peterse, JL; van de Vijver, MJ; de Vries, EGE

    Background: High-dose chemotherapy in the adjuvant treatment of breast cancer has been abandoned by many. Patients and methods: 885 patients with stage III primary breast cancer and four or more axillary lymph node metastases were randomised to receive either five courses of FEC (fluorouracil,

  15. Clinical approaches involving thrombopoietin to shorten the period of thrombocytopenia after high-dose chemotherapy

    NARCIS (Netherlands)

    Tijssen, Marloes R.; van der Schoot, C. Ellen; Voermans, Carlijn; Zwaginga, Jaap Jan

    2006-01-01

    High-dose chemotherapy followed by a peripheral blood stem cell transplant is successfully used for a wide variety of malignancies. A major drawback, however, is the delay in platelet recovery. Several clinical strategies using thrombopoietin (Tpo) have been developed in an attempt to speed up

  16. High-dose chemotherapy : studies on supportive care, quality of life and late effects of treatment

    NARCIS (Netherlands)

    Nieboer, Peter

    2008-01-01

    Drug resistance is a major problem in the treatment of malignancies. Based on steep dose-response relationship for certain chemotherapeutic drugs in vitro on tumor cell survival, high-dose chemotherapy was considered of interest for the treatment of malignancies. Introduction of autologous

  17. Relationship between irreversible alopecia and exposure to cyclophosphamide, thiotepa and carboplatin (CTC) in high-dose chemotherapy

    NARCIS (Netherlands)

    de Jonge, M. E.; Mathôt, R. A. A.; Dalesio, O.; Huitema, A. D. R.; Rodenhuis, S.; Beijnen, J. H.

    2002-01-01

    Reversible alopecia is a commonly observed, important and distressing complication of chemotherapy. Permanent alopecia, however, is rare after standard-dose therapy, but has occasionally been observed after high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin (CTC). We evaluated

  18. Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance?

    Science.gov (United States)

    Day, Troy; Read, Andrew F.

    2016-01-01

    High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the best approach for controlling resistance therefore depends on the relative strengths of these processes. These opposing processes typically lead to a unimodal relationship between drug pressure and resistance emergence. As a result, the optimal drug dose lies at either end of the therapeutic window of clinically acceptable concentrations. We illustrate our findings with a simple model that shows how a seemingly minor change in parameter values can alter the outcome from one where high-dose chemotherapy is optimal to one where using the smallest clinically effective dose is best. A review of the available empirical evidence provides broad support for these general conclusions. Our analysis opens up treatment options not currently considered as resistance management strategies, and it also simplifies the experiments required to determine the drug doses which best retard resistance emergence in patients. PMID:26820986

  19. Inhibitory effect of sequential combined chemotherapy and radiotherapy on growth of implanted tumor in mice

    International Nuclear Information System (INIS)

    Okada, Kouji

    1983-01-01

    Sequential chemotherapy using FT-207, adriamycin and mitomycin C followed by radiotherapy was attempted to achieve effective inhibition against implanted tumor in C57BL/6 black mice bearing YM-12 tumors. Sequential combined chemotherapy was more effective than single drug chemotherapy or combined chemotherapy of other drugs. Addition of radiotherapy to the sequential combined chemotherapy was successful for enhancing therapeutic effect. (author)

  20. Effect of colony-stimulating factor and conventional- or high-dose chemotherapy on FDG uptake in bone marrow

    International Nuclear Information System (INIS)

    Kazama, Toshiki; Swanston, Nancy; Podoloff, Donald A.; Macapinlac, Homer A.

    2005-01-01

    Granulocyte or granulocyte-macrophage colony stimulating factor (CSF), usually used in conjunction with chemotherapy, may interfere with the 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) reading. The purpose of this study is to evaluate the effects of CSF, conventional-or high-dose chemotherapy on bone marrow FDG uptake. Two hundred and forty-one FDG PET scans obtained in 163 patients with lymphoma and no pathologically and radiologically proven bone marrow involvement were analyzed. The standardized uptake value (SUV) of each patient's spine was measured. Among patients with no recent history of CSF use, the average SUV in 36 patients with no history of chemotherapy was 1.60±0.34, that in 49 patients with a history of conventional-dose chemotherapy was 1.37±0.32, and that in 12 patients with a history of high-dose chemotherapy was 1.26±0.25 (P=0.008 and 0.002, respectively by Mann-Whitney U test). In 80 patients treated with conventional-dose chemotherapy and CSF, the average SUV after discontinuation of CSF was as follows: 0-7 days, 2.37±1.19; 8-14 days: 2.04±0.67; 15-21 days: 1.87±0.52; 22-30 days: 1.59±0.18; 31-90 days: 1.54±0.36. In 45 patients treated with high-dose chemotherapy and CSF, no significant increase in bone marrow uptake was seen in most of them. Bone marrow FDG uptake may be increased by CSF treatment and may be decreased by chemotherapy. In patients treated with conventional-dose chemotherapy and CSF, increased marrow uptake will return to the pretreatment value approximately 1 month after discontinuation of CSF. (orig.)

  1. HIGH-DOSE CHEMOTHERAPY WITH STEM-CELL REINFUSION AND GROWTH-FACTOR SUPPORT FOR SOLID TUMORS

    NARCIS (Netherlands)

    DEVRIES, EGE; DEGRAAF, H; VANDERGRAAF, WTA; MULDER, NH; Boonstra, A.

    1995-01-01

    With the help of stem cell reinfusion and hematopoietic growth factors, it is possible to get up to a ten-fold dose increase for certain chemotherapeutic drugs, A number of reasons may have made high-dose chemotherapy less dangerous and the fore more acceptable in a more upfront treatment setting,

  2. Marked improvement by high-dose chemotherapy and autologous stem cell transplantation in a case of light chain deposition disease.

    Science.gov (United States)

    Matsuzaki, Keiichi; Ohsawa, Isao; Nishitani, Tomohito; Takeda, Yukihiko; Inoshita, Hiroyuki; Ishii, Masaya; Takagi, Miyuki; Horikoshi, Satoshi; Tomino, Yasuhiko

    2011-01-01

    A 55-year-old woman presented with heavy proteinuria (6.2 g/day) in April 2007. Because monoclonal IgG-k was detected in serum and urine samples, bone marrow aspiration and renal biopsy were performed. She was diagnosed with plasma cell dyscrasia because a bone marrow aspiration specimen showed plasma cells at 6.1%. Renal tissues revealed the formation of nodular glomerulosclerosis which was negative for Congo-red staining. Renal immunohistochemistry showed positive staining for kappa light chains in the nodular lesions, proximal tubules and part of Bowman's capsules. Her renal involvement was diagnosed as light chain deposition disease. Proteinuria disappeared and renal function stabilized after high-dose chemotherapy and autologous stem cell transplantation. It appears that an early initiation of active therapy such as high-dose chemotherapy and autologous stem cell transplantation may be beneficial for patients with light chain deposition disease.

  3. Radiotherapy after high-dose chemotherapy and peripheral blood stem cell support in high-risk breast cancer

    International Nuclear Information System (INIS)

    Hoeller, Ulrike; Heide, Juergen; Kroeger, Nicolaus; Krueger, William; Jaenicke, Fritz; Alberti, Winfried

    2002-01-01

    Purpose: To assess the toxicity and efficacy of radiotherapy with respect to locoregional control after adjuvant high-dose chemotherapy for patients with breast cancer. At first, radiotherapy was withheld because of toxicity concerns, but it was introduced in 1995 because of reported high locoregional relapse rates. Methods and Materials: Between 1992 and 1998, 40 patients with Stage II-III high-risk breast cancer received adjuvant high-dose chemotherapy consisting of thiotepa, mitoxantrone, and cyclophosphamide and peripheral blood stem cell support after four cycles of induction chemotherapy. The chest wall or breast, as well as the supraclavicular nodes, were irradiated with electrons and photons to a median dose of 50.4 Gy in 20 patients. Six additional patients received only supraclavicular irradiation to a median dose of 50.4 Gy. Acute toxicity was scored clinically. Pulmonary function tests were performed in 14 irradiated patients before high-dose chemotherapy and 1.1-4.4 years (median 1.6) after irradiation. The median follow-up time of living patients was 33 vs. 67 months in irradiated (n=26) and nonirradiated (n=14) patients, respectively. Results: G2 and G3 hematologic toxicity occurred in 1 patient each. No clinical pneumonitis or clinical impairment of lung function was observed. After 1-2 years, the lung function tests showed only minor changes in 4 patients. The 3-year locoregional control rate was 92% in the irradiated patients vs. 58% in the nonirradiated patients (p=0.049, actuarial analysis). Conclusion: In this series, adjuvant radiotherapy after adjuvant chemotherapy for breast cancer appeared well tolerated, with improved local regional control and without significant side effects. Longer follow-up and more patient accrual, as well as Phase III trials, are necessary for confirmation

  4. High-dose Extended-Field Irradiation and High-Dose-Rate Brachytherapy With Concurrent Chemotherapy for Cervical Cancer With Positive Para-Aortic Lymph Nodes

    International Nuclear Information System (INIS)

    Kim, Young Seok; Kim, Jong Hoon; Ahn, Seung Do; Lee, Sang-wook; Shin, Seong Soo; Nam, Joo-Hyun; Kim, Young-Tak; Kim, Yong-Man; Kim, Jong-Hyeok; Choi, Eun Kyung

    2009-01-01

    Purpose: To determine the efficacy and toxicity of extended-field radiotherapy (RT) with concurrent platinum-based chemotherapy in patients with uterine cervical carcinoma and positive para-aortic nodes. Methods and Materials: We retrospectively reviewed the results for 33 women with Stage IB-IVB cervical cancer. Each patient had received 59.4 Gy, including a three-dimensional conformal boost to the para-aortic lymph nodes and 41.4-50.4 Gy of external beam radiotherapy to the pelvis. Each patient also underwent six or seven applications of high-dose-rate brachytherapy (median, 5 Gy to point A at each session). Results: The median follow-up period of surviving patients was 39 months. The most common acute toxicity was hematologic, observed in 23 women. Severe acute and late gastrointestinal toxicity was observed in 3 and 4 patients, respectively. More than three-quarters of patients showed a complete response, encompassing the primary mass, metastatic pelvic, and para-aortic lymph nodes. Of the 33 women, 15 had no evidence of disease, 6 had persistent disease, 4 developed in-field failures, and 6 developed distant failures. The 5-year overall and disease-free survival rate was 47% and 42%, respectively. Conclusion: Concurrent chemoradiotherapy with extended-field radiotherapy is feasible in women with uterine cervical carcinoma and positive para-aortic lymph nodes, with acceptable late morbidity and a high survival rate, although it was accompanied by substantial acute toxicity.

  5. High-dose 8% capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy: single-center experience.

    Science.gov (United States)

    Filipczak-Bryniarska, Iwona; Krzyzewski, Roger M; Kucharz, Jakub; Michalowska-Kaczmarczyk, Anna; Kleja, Justyna; Woron, Jarosław; Strzepek, Katarzyna; Kazior, Lucyna; Wordliczek, Jerzy; Grodzicki, Tomasz; Krzemieniecki, Krzysztof

    2017-08-17

    High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded. Pain was evaluated with Numeric Rating Scale prior to treatment with high-dose capsaicin and after 1.8 day and after 8 and 12 weeks after introducing treatment. Patients were divided into two groups accordingly to the amount of neurotoxic agent that caused neuropathy (high sensitivity and low sensitivity group). Most frequent symptoms of chemotherapy-induced neuropathy were: pain (88.89%), paresthesis (100%), sock and gloves sensation (100%) and hypoesthesis (100%). Initial pain level was 7.45 ± 1.14. Mean cumulative dose of oxaliplatin after which patients developed symptoms was 648.07 mg/m 2 . Mean pain level after 12 weeks of treatment was 0.20 ± 0.41. When examined according to high and low sensitivity to neurotoxic agent patients with low sensitivity had higher pain reduction, especially after 8 days after introducing treatment (69.55 ± 12.09 vs. 49.40 ± 20.34%; p = 0.02) and after 12 weeks (96.96 ± 5.56 vs. 83.93 ± 18.59%; p = 0.04). High-dose capsaicin patch is an effective treatment for pain associated with chemotherapy-induced neuropathy in patients treated with oxaliplatin. Patients with lower sensitivity to neurotoxic agents have better response to treatment and pain reduction.

  6. Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

    International Nuclear Information System (INIS)

    Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

    1987-01-01

    Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82 Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity

  7. Evaluation of an every-other-day palonosetron schedule to control emesis in multiple-day high-dose chemotherapy.

    Science.gov (United States)

    Mirabile, Aurora; Celio, Luigi; Magni, Michele; Bonizzoni, Erminio; Gianni, Alessandro Massimo; Di Nicola, Massimo

    2014-12-01

    Efficacy of intermittent palonosetron dosing in patients undergoing multiple-day, high-dose chemotherapy (HDC) was investigated. Fifty-eight patients received palonosetron (0.25 mg intravenous [iv.]) every other day plus daily dexamethasone (8 mg iv. twice daily) dosing. The primary end point was complete control (CC; no emesis, no rescue anti-emetics, and no more than mild nausea) in the overall acute-period (until 24 h after chemotherapy completion). Acute-period CC occurred in 81% and 50% of patients receiving palonosetron and ondansetron (historical control cohort), respectively. Palonosetron (odds ratio [OR]: 4.37; p = 0.001) and a longer duration of HDC regimen (OR: 3.47; p = 0.011) independently predicted a better anti-emetic outcome. Palonosetron every other day plus daily dexamethasone is an effective anti-emetic coverage in patients undergoing HDC.

  8. High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors.

    Science.gov (United States)

    Spugnini, Enrico P; Buglioni, Sabrina; Carocci, Francesca; Francesco, Menicagli; Vincenzi, Bruno; Fanciulli, Maurizio; Fais, Stefano

    2014-08-21

    The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. A very efficient mechanism of tumor resistance to drugs is the proton pumps-mediated acidification of tumor microenvironment. Metronomic chemotherapy has shown efficacy in adjuvant fashion as well as in the treatment of pets with advanced disease. Moreover, we have shown in veterinary clinical settings that pre-treatment with proton-pumps inhibitors (PPI) increases tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer have been recruited to be treated by a combination of metronomic chemotherapy and high dose PPIs and their responses have been matched to those of a historical control of ten patients treated with metronomic chemotherapy alone. Single arm, non randomized phase II open study, with historical control group, evaluating safety and efficacy of the combination of metronomic chemotherapy and alkalization. Twenty-four companion animals (22 dogs and 2 cats) were treated adding to their metronomic chemotherapy protocol the pump inhibitor lansoprazole at high dose, and a water alkalizer. Their responses have been evaluated by clinical and instrumental evaluation and matched to those of the control group. The protocol was overall well tolerated, with only two dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response, in the alkalized cohort, 18 out of 24 had partial or complete responses (75%), two patients had a stable disease and the remaining patients experienced no response or progressive disease. On the other hand, only one patient in the control group experienced a complete response (10%) and three other experienced short lived responses. Median time to terminal event was 34 weeks for the experimental group versus 2 weeks in the controls (p= 0.042). Patient alkalization has shown to be well tolerated and to increase tumor response

  9. Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: Converging results from multimodal magnetic resonance imaging

    NARCIS (Netherlands)

    de Ruiter, Michiel B.; Reneman, Liesbeth; Boogerd, Willem; Veltman, Dick J.; Caan, Matthan; Douaud, Gwenaëlle; Lavini, Cristina; Linn, Sabine C.; Boven, Epie; van Dam, Frits S. A. M.; Schagen, Sanne B.

    2012-01-01

    The neural substrate underlying cognitive impairments after chemotherapy is largely unknown. Here, we investigated very late (>9 years) effects of adjuvant high-dose chemotherapy on brain white and gray matter in primary breast cancer survivors (n = 17) with multimodal magnetic resonance imaging

  10. Effect of Concurrent High-Dose Cisplatin Chemotherapy and Conformal Radiotherapy on Cervical Esophageal Cancer Survival

    International Nuclear Information System (INIS)

    Huang Shaohui; Lockwood, Gina; Brierley, James; Cummings, Bernard; Kim, John; Wong, Rebecca; Bayley, Andrew; Ringash, Jolie

    2008-01-01

    Purpose: To determine whether a change in treatment policy to conformal, elective nodal radiotherapy and concurrent high-dose cisplatin improved survival for cervical esophageal cancer patients. Methods and Materials: All cervical esophageal cancer patients treated between 1997 and 2005 were restaged (1983 American Joint Committee on Cancer criteria). Patients treated before 2001 (previous cohort [PC]) were compared with those treated from 2001 onward (recent cohort [RC]). The PC institutional chemoradiotherapy protocol was 54 Gy in 20 fractions within 4 weeks, with 5-fluorouracil (1,000 mg/m 2 ) on Days 1-4 and either mitomycin C (10 mg/m 2 ) or cisplatin (75 mg/m 2 ) on Day 1. The RC institutional chemoradiotherapy protocol was conformal radiotherapy, 70 Gy in 35 fractions within 7 weeks, to the primary tumor and elective nodes, with high-dose cisplatin (100 mg/m 2 ) on Days 1, 22, and 43. Results: The median follow-up was 3.1 years (PC, 8.1 and RC, 2.3). Of 71 patients (25 women and 46 men), 21 of 29 in the PC and 29 of 42 in the RC were treated curatively (curative subgroup, n = 50). Between the two groups, no differences in overall survival or locoregional relapse-free survival were seen. The overall survival rate at 2 and 5 years was 35% (range, 24-47%) and 21% (range, 12-32%) in the whole group and 46% (range 32-60%) and 28% (range, 15-42%) in the curative group, respectively. In the curative group, no statistically significant prognostic factors were found. Trends toward better locoregional relapse-free survival were seen in women (2-year rate, 73% vs. for men, 36%; p = 0.08) and in patients aged >64 years (2-year rate, 68% vs. age ≤64 years, 34%; p = 0.10). Conclusion: No survival improvement could be demonstrated after changing the treatment policy to high-dose cisplatin-based, conventionally fractionated conformal chemoradiotherapy. Female gender and older age might predict for better outcomes

  11. Treatment of small cell carcinoma of lung with combined high dose mediastinal irradiation, whole brain prophylaxis and chemotherapy

    International Nuclear Information System (INIS)

    Shank, B.; Natale, R.B.; Hilaris, B.S.; Wittes, R.E.

    1981-01-01

    Survival of patients with small cell carcinoma of lung, treated on a new combined radiotherapy-chemotherapy protocol, compares favorably with other regimens in the literature and our own previous combined approaches. Radiation, given after induction chemotherapy, consisted of whole brain prophylaxis in all 44 evaluable patients. Patients with limited disease were also treated to the primary and mediastinum to a high dose (5000 rad equivalent) using multiple fields. The new chemotherapy regimen consisted of induction with cyclophosphamide, doxorubicin, and vincristine alternated with cis-platinum and VP-16 (an epipodophyllotoxin) for two cycles, followed by consolidation with low dose cyclophosphamide and vincristine concurrent with irradiation. Patients with limited disease who achieved less than complete response, and all patients with extensive disease were not continued on maintenance chemotherapy. Out of 24 evaluable patients with limited disease, there was 73% survival at 1 year by life-table analysis, measured from treatment initiation. After induction, 16/24 of these limited disease patients were CR (complete responders): 20/24 were CR at completion of their irradiation. Out of 20 evaluable patients with extensive disease, there was 59% survival at 1 year by life-table analysis. Only 4/44 (9%) brain parenchymal relapses occurred, one at 3 months and one at 6 months after local failure and two in patients who did not become CRs, implicating a possible re-seeding mechanism. Five patients had central nervous system relapses outside of brain parenchyma (spinal epidural and leptomeningeal); in three patients this was the initial site of failure. Significant complications included leukopenia (50%) and thrombocytopenia (24%) primarily during induction, and chronic pulmonary fibrosis (25%), possibly contributing to two deaths

  12. Bismuth adjuvant ameliorates adverse effects of high-dose chemotherapy in patients with multiple myeloma and malignant lymphoma undergoing autologous stem cell transplantation

    DEFF Research Database (Denmark)

    Hansen, Per Boye; Penkowa, Milena

    2017-01-01

    show for the first time that bismuth significantly reduces grade 2 stomatitis, febrile neutropenia and infections caused by melphalan in multiple myeloma, where adverse effects also were significantly linked to gender. In lymphoma patients, bismuth significantly reduces diarrhoea relative to placebo......PURPOSE: High-dose chemotherapy prior to autologous stem cell transplantation (ASCT) leads to adverse effects including mucositis, neutropenia and bacteremia. To reduce the toxicity, we treated myeloma and lymphoma patients with peroral bismuth as an adjuvant to chemotherapy to convey...

  13. High-dose chemotherapy followed by autologous stem cell transplantation for metastatic rhabdomyosarcoma--a systematic review.

    Directory of Open Access Journals (Sweden)

    Frank Peinemann

    Full Text Available INTRODUCTION: Patients with metastatic rhabdomyosarcoma (RMS have a poor prognosis. The aim of this systematic review is to investigate whether high-dose chemotherapy (HDCT followed by autologous hematopoietic stem cell transplantation (HSCT in patients with metastatic RMS has additional benefit or harm compared to standard chemotherapy. METHODS: Systematic literature searches were performed in MEDLINE, EMBASE, and The Cochrane Library. All databases were searched from inception to February 2010. PubMed was searched in June 2010 for a last update. In addition to randomized and non-randomized controlled trials, case series and case reports were included to complement results from scant data. The primary outcome was overall survival. A meta-analysis was performed using the hazard ratio as primary effect measure, which was estimated from Cox proportional hazard models or from summary statistics of Kaplan Meier product-limit estimations. RESULTS: A total of 40 studies with 287 transplant patients with metastatic RMS (age range 0 to 32 years were included in the assessment. We identified 3 non-randomized controlled trials. The 3-year overall survival ranged from 22% to 53% in the transplant groups vs. 18% to 55% in the control groups. Meta-analysis on overall survival in controlled trials showed no difference between treatments. Result of meta-analysis of pooled individual survival data of case series and case reports, and results from uncontrolled studies with aggregate data were in the range of those from controlled data. The risk of bias was high in all studies due to methodological flaws. CONCLUSIONS: HDCT followed by autologous HSCT in patients with RMS remains an experimental treatment. At present, it does not appear justifiable to use this treatment except in appropriately designed controlled trials.

  14. Fatigue and Relating Factors in High-Risk Breast Cancer Patients Treated With Adjuvant Standard or High-Dose Chemotherapy: A Longitudinal Study

    NARCIS (Netherlands)

    Nieboer, P.; Buijs, C.; Rodenhuis, S.; Seynaeve, C.; Beex, L.V.A.M.; Wall, E. van der; Richel, D.J.; Nooij, M.A.; Voest, E.E.; Hupperets, P.; Mulder, N.H.; Graaf, W.T.A. van der; TenVergert, E.M.; Tinteren, H. van; Vries, E.G.E. de

    2005-01-01

    PURPOSE Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to posttreatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients.

  15. Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or high-dose chemotherapy: a longitudinal study.

    NARCIS (Netherlands)

    Nieboer, P.; Buijs, C.; Rodenhuis, S.; Seynaeve, C.; Beex, L.V.A.M.; Wall, E. van der; Richel, D.J.; Nooij, M.A.; Voest, E.E.; Hupperets, P.S.G.J.; Mulder, N.H.; Graaf, W.T.A. van der; Vergert, E.M. ten; Tinteren, H.L.G. van; Vries, E.G.F. de

    2005-01-01

    PURPOSE: Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients.

  16. Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or high-dose chemotherapy: a longitudinal study

    NARCIS (Netherlands)

    Nieboer, Peter; Buijs, Ciska; Rodenhuis, Sjoerd; Seynaeve, Caroline; Beex, Louk V. A. M.; van der Wall, Elsken; Richel, Dick J.; Nooij, Marianne A.; Voest, Emile E.; Hupperets, Pierre; Mulder, Nanno H.; van der Graaf, Winette T. A.; TenVergert, Els M.; van Tinteren, Harm; de Vries, Elisabeth G. E.

    2005-01-01

    PURPOSE: Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients.

  17. Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or high-dose chemotherapy : A longitudinal study

    NARCIS (Netherlands)

    Nieboer, P; Buijs, C; Rodenhuis, S; Seynaeve, C; Beex, LVAM; van der Wall, E; Richel, DJ; Nooij, MA; Voest, EE; Hupperets, P; Mulder, NH; van der Graaf, WTA; TenVergert, EM; van Tinteren, H; de Vries, EGE

    2005-01-01

    Purpose Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients.

  18. Early stage cost-effectiveness analysis of a BRCA1-like test to detect triple negative breast cancers responsive to high dose alkylating chemotherapy

    NARCIS (Netherlands)

    Miquel-Cases, Anna; Steuten, Lotte Maria Gertruda; Retel, Valesca P.; van Harten, Willem H.

    2015-01-01

    Purpose Triple negative breast cancers (TNBC) with a BRCA1-like profile may benefit from high dose alkylating chemotherapy (HDAC). This study examines whether BRCA1-like testing to target effective HDAC in TNBC patients can be more cost-effective than treating all patients with standard

  19. Ovarian function in survivors of childhood medulloblastoma: Impact of reduced dose craniospinal irradiation and high-dose chemotherapy with autologous stem cell rescue.

    Science.gov (United States)

    Balachandar, Sadana; Dunkel, Ira J; Khakoo, Yasmin; Wolden, Suzanne; Allen, Jeffrey; Sklar, Charles A

    2015-02-01

    Data on ovarian function (OvF) in medulloblastoma (MB) survivors is limited, with most studies describing outcomes in survivors treated with craniospinal irradiation (CSI) doses >24 Gy ± standard chemotherapy. The objective of the current study is to report on OvF: (i) across a range of CSI doses; and (ii) following high-dose chemotherapy with autologous stem cell rescue (ASCR). Retrospective review of female MB survivors who were diagnosed in childhood and followed at Memorial Sloan Kettering Cancer Center. Patients were divided into three groups: (i) CSI ≤24 Gy +/- standard chemotherapy; (ii) CSI ≥35 Gy +/- standard chemotherapy; and (iii) high-dose chemotherapy with ASCR +/- CSI. Primary ovarian dysfunction (POD) occurred in 2/17 subjects in group 1, 3/9 subjects in group 2 and 5/5 subjects in group 3 (P < 0.01). Normalization of function was noted in four subjects with POD. Persistent POD requiring hormone replacement (POF) was observed in 1/17 subjects in group 1, 2/9 in group 2, and 3/5 in group 3 (P = 0.02). Neither age at treatment nor type of standard chemotherapy correlated with risk of POD or POF. Both POD and POF appear to occur in a small proportion of patients who are treated with contemporary doses of CSI +/- standard chemotherapy. However, ovarian dysfunction requiring hormone replacement therapy is common following high-dose chemotherapy associated with ASCR. These findings will assist clinicians in counseling patients regarding fertility preservation and risk of impaired ovarian function/future fertility. Pediatr Blood Cancer 2015;62:317-321. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

  20. Risk Factors of anemia in head and neck cancer patients undergoing chemotherapy with high-dose cisplatin

    Directory of Open Access Journals (Sweden)

    Johan Kurnianda

    2008-12-01

    Full Text Available Cisplatin is well-known for its effectiveness against cancer, as well as its toxicity to human tissues. Of several documented side effects, anemia was reported to have significant association with decreased quality of life. This study was conducted to investigate development of cisplatin-induced anemia, and to identify independent factors contributing to anemia. Clinical data from head and neck cancer patients treated with high-dose cisplatin between December 2002 and December 2005 were obtained in this study. Incidence and risk factors of anemia were assessed in a model including age, sex, baseline hemoglobin level, baseline creatinine clearance, and occurrence of distant metastases. Multivariate logistic regression was used to define independent predictors of anemia. Among 86 eligible patients, 26 (30.2% developed anemia, defined as Hb level lower than 11 g/dL. Age > 55 years old (RR = 2.2, 95% CI, 1.2-4.0, female sex (RR = 2.0, 95% CI, 1.2-3.8, baseline Hb ≤ 13 g/dL (RR = 4.2, 95% CI, 1.9-9.4 and baseline CrCl < 50 mL/min (RR = 2.9, 95% CI, 1.7-5.1 were significantly correlated with incidence of anemia (P < 0.05. In multivariate analysis, baseline Hb and baseline CrCl were identified as independent risk factors for anemia. However, considerable confounding was observed in baseline CrCl after stratified by age (aRR = 2.2, 95% CI, 1.1-4.7. Thus, baseline Hb level was the strongest predictor of anemia. The findings suggested that baseline Hb and CrCl were useful to recognize cisplatin-treated patients at risk for anemia who might benefits from preventive measures. (Med J Indones 2008; 17: 248-54Keywords: anemia, cisplatin, chemotherapy, hemoglobin, creatinine clearance

  1. The retreatment of carboplatin via high-dose intraperitoneal chemotherapy in patients with a history of a hypersensitivity reaction

    NARCIS (Netherlands)

    Kerkhof, M.H.; Ruiz Zapata, A.M.; Bril, H.; Bleeker, M.C.G.; Belien, J.A.M.; Stoop, R.; Helder, M.N.

    2014-01-01

    A hypersensitivity reaction attributed to platinum-based chemotherapy is a relatively common occurrence. Hyperthermic intraperitoneal chemotherapy potentially facilitates the safe retreatment of platinum therapy following this complication. We describe 3 ovarian cancer patients who were successfully

  2. Preliminary results of concurrent chemotherapy and radiation therapy using high-dose-rate brachytherapy for cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyung Ja; Lee, Ji Hye; Lee, Re Na; Suh, Hyun Suk [Ewha Womans University College of Medicine, Seoul (Korea, Republic of)

    2006-09-15

    To determine the efficacy and safety of concurrent chemotherapy and radiation therapy with high-dose-rate brachytherapy for cervical cancer. From January 2001 to December 2002, 30 patients with cervical cancer were treated with concurrent chemotherapy (cisplatin and 5-FU) and definitive radiation therapy. The median age was 58 (range 34 {approx} 74) year old. The pathology of the biopsy sections was squamous cell carcinoma in 29 patients and one was adenocarcinoma. The distribution to FIGO staging system was as follow: stage IB, 7 (23%); IIA, 3 (10%); IIB, 12 (40%); IIIA, 3 (10%); IIIB, 5 (17%). All patients received pelvic external beam irradiation (EBRT) to a total dose of 45 {approx} 50.4 Gy (median: 50.4 Gy) over 5 {approx} 5.5 weeks. Ir-192 HDR intracavity brachytherapy (ICBT) was given after a total dose of 41.1 Gy. HDR-ICBT was performed twice a week, with a fraction point. A dose of 4 Gy and median dose to point A was 28 Gy (range: 16 {approx} 32 Gy) in 7 fractions. The median cumulative biologic effective dose (BED) at point A (EBRT + ICBT) was 88 Gy{sub 10} (range:77 {approx} 94 Gy{sub 10}). The median cumulative BED at ICRU 38 reference point (EBRT + ICBT) was 131 Gy{sub 3} (range: 122 {approx} 140 Gy{sub 3}) at point A, 109 Gy{sub 3} (range:88{approx} 125 Gy{sub 3}) at the rectum and 111 Gy{sub 3} (range: 91 {approx} 123 Gy{sub 3}) at the urinary bladder. Cisplatin (60 mg/m{sup 2}) and 5-FU (1,000 mg/m{sup 2}) was administered intravenously at 2 weeks interval from the first day of radiation for median 5 (range:2 {approx} 6) cycles. The assessment was performed at 1 month after completion of radiation therapy by clinical examination and CT scan. The median follow-up time was 36 months (range:8{approx} 50 months). The complete response rate after concurrent chemo radiation therapy was 93.3%. The 3-yr actuarial pelvic control rate was 87% and 3-yr actuarial overall survival and disease-free survival rate was 93% and 87%, respectively. The local failure

  3. Preliminary results of concurrent chemotherapy and radiation therapy using high-dose-rate brachytherapy for cervical cancer

    International Nuclear Information System (INIS)

    Lee, Kyung Ja; Lee, Ji Hye; Lee, Re Na; Suh, Hyun Suk

    2006-01-01

    To determine the efficacy and safety of concurrent chemotherapy and radiation therapy with high-dose-rate brachytherapy for cervical cancer. From January 2001 to December 2002, 30 patients with cervical cancer were treated with concurrent chemotherapy (cisplatin and 5-FU) and definitive radiation therapy. The median age was 58 (range 34 ∼ 74) year old. The pathology of the biopsy sections was squamous cell carcinoma in 29 patients and one was adenocarcinoma. The distribution to FIGO staging system was as follow: stage IB, 7 (23%); IIA, 3 (10%); IIB, 12 (40%); IIIA, 3 (10%); IIIB, 5 (17%). All patients received pelvic external beam irradiation (EBRT) to a total dose of 45 ∼ 50.4 Gy (median: 50.4 Gy) over 5 ∼ 5.5 weeks. Ir-192 HDR intracavity brachytherapy (ICBT) was given after a total dose of 41.1 Gy. HDR-ICBT was performed twice a week, with a fraction point. A dose of 4 Gy and median dose to point A was 28 Gy (range: 16 ∼ 32 Gy) in 7 fractions. The median cumulative biologic effective dose (BED) at point A (EBRT + ICBT) was 88 Gy 10 (range:77 ∼ 94 Gy 10 ). The median cumulative BED at ICRU 38 reference point (EBRT + ICBT) was 131 Gy 3 (range: 122 ∼ 140 Gy 3 ) at point A, 109 Gy 3 (range:88∼ 125 Gy 3 ) at the rectum and 111 Gy 3 (range: 91 ∼ 123 Gy 3 ) at the urinary bladder. Cisplatin (60 mg/m 2 ) and 5-FU (1,000 mg/m 2 ) was administered intravenously at 2 weeks interval from the first day of radiation for median 5 (range:2 ∼ 6) cycles. The assessment was performed at 1 month after completion of radiation therapy by clinical examination and CT scan. The median follow-up time was 36 months (range:8∼ 50 months). The complete response rate after concurrent chemo radiation therapy was 93.3%. The 3-yr actuarial pelvic control rate was 87% and 3-yr actuarial overall survival and disease-free survival rate was 93% and 87%, respectively. The local failure rate was 13% and distant metastatic rate was 3.3%. The crude rate of minor hematologic

  4. High-dose chemotherapy with stem cell rescue in the primary treatment of metastatic and pelvic osteosarcoma: final results of the ISG/SSG II study.

    Science.gov (United States)

    Boye, Kjetil; Del Prever, Adalberto Brach; Eriksson, Mikael; Saeter, Gunnar; Tienghi, Amelia; Lindholm, Paula; Fagioli, Franca; Skjeldal, Sigmund; Ferrari, Stefano; Hall, Kirsten Sundby

    2014-05-01

    Patients with metastatic osteosarcoma at diagnosis or axial primary tumors have a poor prognosis. The aim of the study was to evaluate the feasibility and efficacy of intensified treatment with high-dose chemotherapy (HDCT) and stem cell rescue in this group. From May 1996 to August 2004, 71 patients were included in a Scandinavian-Italian single arm phase II study. Preoperative chemotherapy included methotrexate, doxorubicin, cisplatin and ifosfamide, and postoperative treatment consisted of two cycles of doxorubicin, one cycle of cyclophosphamide and etoposide and two courses of high-dose etoposide and carboplatin with stem cell rescue. Twenty-nine patients (43%) received two courses and 10 patients (15%) received one course of HDCT. HDCT was associated with significant toxicity, but no treatment-related deaths were recorded. Fourteen patients (20%) had disease progression before completion of the study protocol, and only 29/71 patients (41%) received the full planned treatment. Median event-free survival (EFS) was 18 months, and estimated 5-year EFS was 27%. Median overall survival (OS) was 34 months, and estimated 5-year OS was 31%. When patients who did not receive HDCT due to disease progression were excluded, there was no difference in EFS (P = 0.72) or OS (P = 0.49) between patients who did or did not receive HDCT. The administration of high-dose chemotherapy with stem cell rescue was feasible, but associated with significant toxicity. Patient outcome seemed comparable to previous studies using conventional chemotherapy. We conclude that HDCT with carboplatin and etoposide should not be further explored as a treatment strategy in high-risk osteosarcoma. © 2013 Wiley Periodicals, Inc.

  5. Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte-macrophage colony-stimulating factor for hematologic support after high-dose intensification for breast cancer.

    Science.gov (United States)

    Elias, A D; Ayash, L; Anderson, K C; Hunt, M; Wheeler, C; Schwartz, G; Tepler, I; Mazanet, R; Lynch, C; Pap, S

    1992-06-01

    High-dose therapy with autologous marrow support results in durable complete remissions in selected patients with relapsed lymphoma and leukemia who cannot be cured with conventional dose therapy. However, substantial morbidity and mortality result from the 3- to 6-week period of marrow aplasia until the reinfused marrow recovers adequate hematopoietic function. Hematopoietic growth factors, particularly used after chemotherapy, can increase the number of peripheral blood progenitor cells (PBPCs) present in systemic circulation. The reinfusion of PBPCs with marrow has recently been reported to reduce the time to recovery of adequate marrow function. This study was designed to determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPCs alone (without marrow) would result in rapid and reliable hematopoietic reconstitution. Sixteen patients with metastatic breast cancer were treated with four cycles of doxorubicin, 5-fluorouracil, and methotrexate (AFM induction). Patients responding after the first two cycles were administered GM-CSF after the third and fourth cycles to recruit PBPCs for collection by two leukapheresis per cycle. These PBPCs were reinfused as the sole source of hematopoietic support after high doses of cyclophosphamide, thiotepa, and carboplatin. No marrow or hematopoietic cytokines were used after progenitor cell reinfusion. Granulocytes greater than or equal to 500/microL was observed on a median of day 14 (range, 8 to 57). Transfusion independence of platelets greater than or equal to 20,000/microL occurred on a median day of 12 (range, 8 to 134). However, three patients required the use of a reserve marrow for slow platelet engraftment. In retrospect, these patients were characterized by poor baseline bone marrow cellularity and poor platelet recovery after AFM induction therapy. When compared with 29 historical control patients who had received the same high-dose intensification chemotherapy using autologous

  6. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

    Directory of Open Access Journals (Sweden)

    L John Hoffer

    Full Text Available Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type

  7. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

    Science.gov (United States)

    Hoffer, L John; Robitaille, Line; Zakarian, Robert; Melnychuk, David; Kavan, Petr; Agulnik, Jason; Cohen, Victor; Small, David; Miller, Wilson H

    2015-01-01

    Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail. We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement. Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy

  8. Health related quality of life in locally advanced NSCLC treated with high dose radiotherapy and concurrent chemotherapy or cetuximab – Pooled results from two prospective clinical trials

    International Nuclear Information System (INIS)

    Hallqvist, Andreas; Bergman, Bengt; Nyman, Jan

    2012-01-01

    Background: In non-small cell lung cancer (NSCLC) stage III, data on patient reported health-related quality of life (HRQL) are scarce, especially regarding concurrent chemoradiotherapy. Aims: To evaluate HRQL in patients treated with high dose radiotherapy combined with concurrent chemotherapy or the antibody cetuximab. Methods: The study population comprised all patients enroled in either of two phase II trials in locally advanced NSCLC performed in Sweden 2002–2007. The RAKET trial investigated three different ways of increasing local control (accelerated hyperfractionated treatment or concurrent daily or weekly chemotherapy). The Satellite trial evaluated the addition of cetuximab to thoracic irradiation. HRQL was measured at four time points: At baseline, before radiotherapy, 4–6 weeks after radiotherapy and at 3 months follow-up, using the EORTC QLQ-C30 and LC14 set of questionnaires. Results: 154/220 patients (65%) who completed HRQL assessments at all time points were included in the longitudinal study. There was a significant decline over time regarding most functioning measures. Dyspnoea and fatigue gradually deteriorated without recovery after completed treatment. Chemotherapy related symptoms showed a transient deterioration, whereas radiotherapy related esophagitis had not fully recovered at 3 months. Patients with stage IIIA disease tended to recover better regarding global QL, fatigue and dyspnoea compared to patients with stage IIIB. Patients with WHO performance status (PS) 0 reported improved global QL and less fatigue over time compared with PS 1. Concurrent chemotherapy was associated with more pronounced fatigue and dysphagia, and worse global QL compared with concurrent cetuximab. Baseline physical functioning was an independent predictor of overall survival. Conclusion: Patients undergoing high dose thoracic radiotherapy combined with chemotherapy or cetuximab reported a gradual deterioration in functioning, dyspnoea and fatigue, while

  9. Multidisciplinary approach for the esophageal carcinoma with intent to conserve the esophagus centering on high-dose radiotherapy and concurrent chemotherapy

    International Nuclear Information System (INIS)

    Murakami, Masao; Kuroda, Yasumasa; Okamoto, Yoshiaki

    1997-01-01

    Forty-seven patients with operable squamous cell carcinoma of the thoracic esophagus were treated by initial concurrent chemoradiotherapy (CDDP-5 FU-44 Gy) followed by definitive high-dose of radiotherapy (CRT group: 35 patients) or surgery (CRT-S group: 12 patients). Clinical CR rate showed 86% in CRT group; and pathological CR rate 18% in CRT-S group. The overall median survival was 45 months, survival at 1, 3, 5 years being 96%, 52%, 48%, respectively. No treatment-related mortality was observed. The rate of the 'esophagus conservation' was 66%. Our results demonstrated that the multidisciplinary approach with intent to conserve the esophagus centering on high-dose radiotherapy and concurrent chemotherapy provides a significant improvement of both survival and quality of life in patients with operable esophageal carcinoma. (author)

  10. High-dose chemotherapy and auto-SCT for relapsed and refractory Hodgkin's lymphoma patients refractory to first-line salvage chemotherapy but responsive to second-line salvage chemotherapy.

    Science.gov (United States)

    Rauf, Muhammad Shahzad; Maghfoor, Irfan; Elhassan, Tusneem Ahmed M; Akhtar, Saad

    2015-01-01

    Relapsed or primary refractory Hodgkin's lymphoma (HL) patients refractory to first-line salvage chemotherapy (first salvage) and unable to undergo high-dose chemotherapy (HDC) and autologous stem cell transplant (auto-SCT) have very poor outcome. Some patients are offered second-line salvage chemotherapy (second salvage), if they are responsive and may receive HDC auto-SCT. We identified 31 patients (18 males, 13 females) from 1996-2012 who received second salvage prior to auto-SCT. Median age at auto-SCT is 22 years. Patients were grouped as (1) relapsed-refractory (Rel:Ref): patients with prior complete response (CR) and on relapse found refractory to first salvage and received second salvage and (2) refractory-refractory (Ref:Ref): patients refractory to both primary treatment and first salvage and received second salvage. Median follow-up is 63 months (18-170). Disease status after second salvage prior to HDC was CR 16 %, partial response (PR) 71 % and stable disease 13 %. After HDC auto-SCT, CR:PR: progressive disease was observed in 18 (58 %): four (12 %): nine (29 %) patients, respectively. Five-year overall survival (OS) for whole group is 57 % (Rel:Ref vs. Ref:Ref, 73 % vs. 48 %, p = 0.48). Progression-free survival (PFS) for whole group is 52 % (Rel:Ref vs. Ref:Ref, 73 % vs. 40 % respectively, p = 0.11). Second-line salvage is a valid approach with no long-term side effects for those HL patients who do not respond to first-line salvage chemotherapy and they can be candidate of HDC and stem cell transplant with a high ORR, the PFS and OS in relapse-refractory and refractory-refractory group of patients.

  11. Five-year follow-up of survival and relapse in patients who received cryotherapy during high-dose chemotherapy for stem cell transplantation shows no safety concerns.

    Science.gov (United States)

    Svanberg, A; Ohrn, K; Birgegård, G

    2012-11-01

    We have previously published a randomised controlled study of the efficacy of cryotherapy in preventing acute oral mucositis after high-dose chemotherapy for stem cell transplantation. The present study is a 5-year follow-up safety study of survival in these patients. In the previously published study oral cryotherapy (cooling of the oral cavity) during high-dose chemotherapy significantly reduced mucositis grade and opiate use in the treated group. All patients were followed up for at least 5 years with regard to relapse and death rates. Baseline data, transplant complications and mucositis data were compared. Significantly more patients (25/39) who received oral cryotherapy were alive after 5 years compared to 15/39 in the control group (P= 0.025). Relapse rates were similar. The only baseline difference was a lower proportion of patients in complete remission at transplantation in the control group (6 vs. 13, P= 0.047). This 5-year follow-up study gave no support for safety concerns with cryotherapy. © 2012 Blackwell Publishing Ltd.

  12. Reinfusion of autologous lymphocytes with granulocyte-macrophage colony-stimulating factor induces rapid recovery of CD4+ and CD8+ T cells after high-dose chemotherapy for metastatic breast cancer

    NARCIS (Netherlands)

    de Gast, G. C.; Vyth-Dreese, F. A.; Nooijen, W.; van den Bogaard, C. J. C.; Sein, J.; Holtkamp, M. M. J.; Linthorst, G. A. M.; Baars, J. W.; Schornagel, J. H.; Rodenhuis, S.

    2002-01-01

    PURPOSE: Repeated high-dose chemotherapy (HDCT) followed by peripheral-blood progenitor cell (PBPC) transplantation can induce a complete remission in patients with metastatic breast cancer sensitive to standard chemotherapy (CT), but the majority of patients relapse within 1 to 2 years. The immune

  13. An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients

    NARCIS (Netherlands)

    Vollebergh, M. A.; Lips, E. H.; Nederlof, P. M.; Wessels, L. F. A.; Schmidt, M. K.; van Beers, E. H.; Cornelissen, S.; Holtkamp, M.; Froklage, F. E.; de Vries, E. G. E.; Schrama, J. G.; Wesseling, J.; van de Vijver, M. J.; van Tinteren, H.; de Bruin, M.; Hauptmann, M.; Rodenhuis, S.; Linn, S. C.

    Patients and methods: We evaluated this classifier in stage III breast cancer patients, who had been randomly assigned between adjuvant high-dose platinum-based (HD-PB) chemotherapy, a DSB-inducing regimen, and conventional anthracycline-based chemotherapy. Additionally, we assessed BRCA1 loss

  14. Effect of cryoablation sequential chemotherapy on patients with advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Shu-Hui Yao

    2016-03-01

    Full Text Available Objective: To evaluate the effect of cryoablation sequential chemotherapy on patients with advanced non-small cell lung cancer. Methods: A total of 39 cases with advanced non-small cell lung cancer who received cryoablation sequential chemotherapy and 39 cases with advanced non-small cell lung cancer who received chemotherapy alone were selected and enrolled in sequential group and control group, disease progression and survival of two groups were followed up, and contents of tumor markers and angiogenesis molecules in serum as well as contents of T-lymphocyte subsets in peripheral blood were detected. Results: Progressionfree survival and median overall survival (mOS of sequential group were longer than those of control group, and cumulative cases of tumor progression at various points in time were significantly less than those of control group (P<0.05; 1 month after treatment, serum tumor markers CEA, CYFRA21-1 and NSE contents, serum angiogenesis molecules PCDGF, VEGF and HDGF contents as well as CD3+CD4-CD8+CD28-T cell content in peripheral blood of sequential group were significantly lower than those of control group (P<0.05, and contents of CD3+CD4+CD8-T cell and CD3+CD4-CD8+CD28+T cell in peripheral blood were higher than those of control group (P<0.05. Conclusions: Cryoablation sequential chemotherapy can improve the prognosis of patients with advanced non-small cell lung cancer, delay disease progression, prolong survival time, inhibit angiogenesis and improve immune function.

  15. Dose finding study of granisetron in patients receiving high-dose cisplatin chemotherapy. The Granisetron Study Group.

    Science.gov (United States)

    Riviere, A.

    1994-01-01

    The efficacy and safety of three different doses of granisetron (2 micrograms kg-1, group A; 10 micrograms kg-1, group B; 40 micrograms kg-1, group C) were compared in a randomised, double-blind study of 157 patients due to receive high-dose cisplatin therapy (mean dose > 97 mg m-2). In each group, up to two 3 mg rescue doses of granisetron were allowed if more than mild nausea or vomiting occurred. In group A 30.8%, in group B 61.5% and in group C 67.9% of patients were complete responders (i.e. no vomiting or nothing worse than mild nausea) during the first 24 h. These differences are significant between groups A and B, and A and C. There were no statistically significant differences in any efficacy variable between the 10 micrograms kg-1 and 40 micrograms kg-1 groups, although in each case the trend favoured the higher dose. Additional rescue doses resulted in resolved or improved symptoms in 95.3% for the first rescue dose and 93.3% for the second. Over the 7 days of the study, 82.7%, 82.7% and 86.8% of patients in groups A, B and C respectively were treated with granisetron alone. Headache was the most common side-effect, reported by 9.6% of patients; the majority of headaches were mild. There was no difference between the treatment groups regarding the adverse event rate. We concluded that prophylactic doses of 10 or 40 micrograms kg-1 lead to a safe and satisfactory degree of control of nausea and vomiting induced by high-dose cisplatin. PMID:8180032

  16. Sequential response patterns to chemotherapy and radiotherapy in head and neck cancer

    International Nuclear Information System (INIS)

    Hong, W.K.; O'Donoghue, G.M.; Sheetz, S.

    1985-01-01

    Surgery and/or radiotherapy have been the standard therapies for locally advanced squamous cell carcinoma of the head and neck region. Despite major improvement in these therapeutic techniques, the control rate in cases of advanced cancer remains poor. More recently, induction chemotherapy as initial treatment has been used in previously untreated squamous cell carcinoma of the head and neck. For the last 6 years at the Boston Veterans Administration (V.A.) Medical Center, initial induction chemotherapy followed by surgery and/or radiotherapy has been employed in the treatment of advanced head and neck cancer. The use of chemotherapy and radiotherapy has allowed the authors to monitor and correlate sequential response patterns produced by each modality of treatment. The authors have observed that responders to chemotherapy can be predicted to have further response to subsequent radiotherapy

  17. Long-term brain structural magnetic resonance imaging and cognitive functioning in children treated for acute lymphoblastic leukemia with high-dose methotrexate chemotherapy alone or combined with CNS radiotherapy at reduced total dose to 12 Gy

    Energy Technology Data Exchange (ETDEWEB)

    Zajac-Spychala, Olga; Pilarczyk, Jakub; Derwich, Katarzyna; Wachowiak, Jacek [Poznan University of Medical Sciences, Department of Pediatric Oncology, Hematology and Transplantology, Poznan (Poland); Pawlak, Mikolaj A. [Poznan University of Medical Sciences, Department of Neurology and Cerebrovascular Disorders, Poznan (Poland); Karmelita-Katulska, Katarzyna [Poznan University of Medical Sciences, Department of Neuroradiology, Poznan (Poland)

    2017-02-15

    The aim of this study was to assess the long-term side effects of central nervous system prophylaxis (high-dose chemotherapy alone vs chemotherapy and CNS radiotherapy) according to the ALL IC-BFM 2002. Thirty-tree children aged 6.7-19.9 years have been studied. The control group consisted of 12 children newly diagnosed with acute lymphoblastic leukemia. We assessed subcortical gray matter volume using automatic MRI segmentation and cognitive performance to identify differences between two therapeutic schemes and patients prior to treatment. Patients treated with chemotherapy and CNS radiotherapy had smaller hippocampi than two other subgroups and lower IQ score than patients treated with chemotherapy alone. Both treated groups, whether with chemotherapy only or in combination with CNS radiotherapy, had significantly lower volumes of caudate nucleus and performed significantly worse on measures of verbal fluency in comparison with patients prior to treatment. There were no differences in the mean volumes of total white matter, total gray matter, thalamus, putamen, and amygdala between the studied groups. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment was observed, especially in children who received chemotherapy in combination with reduced dose CNS radiotherapy. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment were observed, especially in children who received chemotherapy in combination with CNS radiotherapy. (orig.)

  18. Long-term brain structural magnetic resonance imaging and cognitive functioning in children treated for acute lymphoblastic leukemia with high-dose methotrexate chemotherapy alone or combined with CNS radiotherapy at reduced total dose to 12 Gy

    International Nuclear Information System (INIS)

    Zajac-Spychala, Olga; Pilarczyk, Jakub; Derwich, Katarzyna; Wachowiak, Jacek; Pawlak, Mikolaj A.; Karmelita-Katulska, Katarzyna

    2017-01-01

    The aim of this study was to assess the long-term side effects of central nervous system prophylaxis (high-dose chemotherapy alone vs chemotherapy and CNS radiotherapy) according to the ALL IC-BFM 2002. Thirty-tree children aged 6.7-19.9 years have been studied. The control group consisted of 12 children newly diagnosed with acute lymphoblastic leukemia. We assessed subcortical gray matter volume using automatic MRI segmentation and cognitive performance to identify differences between two therapeutic schemes and patients prior to treatment. Patients treated with chemotherapy and CNS radiotherapy had smaller hippocampi than two other subgroups and lower IQ score than patients treated with chemotherapy alone. Both treated groups, whether with chemotherapy only or in combination with CNS radiotherapy, had significantly lower volumes of caudate nucleus and performed significantly worse on measures of verbal fluency in comparison with patients prior to treatment. There were no differences in the mean volumes of total white matter, total gray matter, thalamus, putamen, and amygdala between the studied groups. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment was observed, especially in children who received chemotherapy in combination with reduced dose CNS radiotherapy. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment were observed, especially in children who received chemotherapy in combination with CNS radiotherapy. (orig.)

  19. Tandem high-dose chemotherapy and auto-SCT for malignant brain tumors in children under 3 years of age.

    Science.gov (United States)

    Sung, K W; Lim, D H; Lee, S H; Yoo, K H; Koo, H H; Kim, J H; Suh, Y-L; Joung, Y S; Shin, H J

    2013-07-01

    In an effort to improve survival and reduce late adverse effects of radiation therapy (RT), 25 children SCT following six cycles of induction chemotherapy. RT was either not given or deferred until 3 years of age if the patient was in CR after tandem HDCT/auto-SCT. Tumors relapsed or progressed in nine patients (five during induction treatment), and two of these patients survived after receiving salvage treatment, including RT. Two patients died due to toxicities during tandem HDCT/auto-SCT. A total of 16 patients survived to a median follow-up period of 52 months (range 18-96) from the time of diagnosis. Four of these patients did not receive RT, two received local RT (L-RT), three received craniospinal RT (CSRT), and seven received both L-RT and CSRT. The 5-year OS and EFS rates were 67.8±9.4% and 55.5±10.0%, respectively. Neuroendocrine and neurocognitive functions evaluated 3 years after tandem HDCT/auto-SCT were acceptable. Our results indicate that tandem HDCT/auto-SCT may improve survival in young children with malignant brain tumors with an acceptable level of risk of long-term toxicity.

  20. Acute Complications After High-Dose Chemotherapy and Stem-Cell Rescue in Pediatric Patients With High-Risk Neuroblastoma Treated in Countries With Different Resources

    Directory of Open Access Journals (Sweden)

    Mahmoud M. Elzembely

    2018-03-01

    Full Text Available Purpose: High-dose chemotherapy with autologous stem-cell rescue (SCR is a key component of high-risk neuroblastoma (HRNB therapy. Carboplatin, etoposide, and melphalan (CEM or busulfan and melphalan (Bu/Mel are the most evaluated, effective high-dose chemotherapy for HRNB on the basis of results from major cooperative group studies. Toxicity profiles vary between these regimens, and practice variation exists regarding the preferred high-dose therapy (HDT. We sought to evaluate the safety of HDT and autologous SCR for HRNB in a resource-limited country (Egypt compared with the resource-rich United States. Patients and Methods: We performed a retrospective comparative review of single CEM-based HDT/SCR outcomes through day 100 for HRNB at the Fred Hutchinson Cancer Research Center (FH in the United States (2005 to 2015 versus Bu/Mel-based HDT at El-Sheikh Zayed Specialized Hospital (SZ in Egypt (2009 to 2015. Results: Forty-four patients at FH and 77 patients at SZ were reviewed. Pretransplant hepatic comorbidities were significantly higher at SZ (29 of 77 v nine of 44; P = .05, with 19 of 77 patients at SZ having hepatitis infection. Engraftment was delayed after SZ-Bu/Mel therapy compared with FH-CEM therapy for neutrophils (median 12 days v 10 days, respectively; P < .001 and platelets (median 20 days v 18 days, respectively; P < .001. Sinusoidal obstruction syndrome occurred later, after SZ-Bu/Mel therapy (median 19 days v 7 days; P = .033, and four of eight cases were fatal (six of eight patients had underlying hepatitis infection, whereas three of three cases after FH-CEM therapy were moderately severe. Resource utilization associated with the number of days with fever, antibiotic use, and the number of transfusions administered was significantly higher after FH-CEM therapy than after SZ-Bu/Mel therapy. Conclusion: Use of autologous stem-cell transplantation is feasible in the context of a resource-limited country.

  1. Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft

    International Nuclear Information System (INIS)

    Fermand, J.P.; Levy, Y.; Gerota, J.; Benbunan, M.; Cosset, J.M.; Castaigne, S.; Seligmann, M.; Brouet, J.C.

    1989-01-01

    Eight patients with stage III aggressive multiple myeloma, refractory to current chemotherapy in six cases, were treated by high-dose chemotherapy (nitrosourea, etoposide, and melphalan) (HDC) and total body irradiation (TBI), followed by autografting with blood stem cells. These cells were previously collected by leukapheresis performed during hematologic recovery following cytotoxic drug-induced bone marrow aplasia. Seven patients were alive 9 to 17 months after HDC-TBI and graft. One died at day 40 from cerebral bleeding. All living patients achieved a 90% or greater reduction in tumor mass. In two cases, a complete remission (CR) has persisted at a follow-up of 15 and 16 months. Three patients have been well and off therapy with stable minimal residual disease (RD) since 10, 11, and 17 months, respectively. A patient in apparent CR and another with RD have relapsed 9 to 12 months posttreatment. Autologous blood-derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. These results, although still preliminary, indicate that HDC and TBI, followed by blood stem cells autograft, which has both practical and theoretical interest over allogeneic or autologous bone marrow transplantation, deserve consideration in selected patients with multiple myeloma

  2. High-dose chemotherapy for patients with high-risk breast cancer: a clinical and economic assessment using a quality-adjusted survival analysis.

    Science.gov (United States)

    Marino, Patricia; Roché, Henri; Moatti, Jean-Paul

    2008-04-01

    The benefit of high-dose chemotherapy (HDC) has not been clearly demonstrated. It may offer disease-free survival improvement at the expense of major toxicity and increasing cost. We evaluated the trade-offs between toxicity, relapse, and costs using a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis. The analysis was conducted in the context of a randomized trial (PEGASE 01) evaluating the benefit of HDC for 314 patients with high-risk breast cancer. A Q-TWiST analysis was first performed to compare HDC with standard chemotherapy. We then used the results of this Q-TWiST analysis to inform a cost per quality-adjusted life-year (QALY) comparison between treatments. Q-TWiST durations were in favor of HDC, whatever the weighting coefficients used for the analysis. This benefit was significant when the weighting coefficient related to the time spent after relapse was low (0.78), HDC offered no benefit. For intermediate values, the results depended on the weighting coefficient attributed to the toxicity period. The incremental cost per QALY ranged from 12,691euro/QALY to 26,439euro/QALY, according to the coefficients used to weight toxicity and relapse. The benefits of HDC outweigh the burdens of treatment for a wide range of utility coefficients. Economic impact is not a barrier to HDC diffusion in this situation. Nevertheless, no significant benefit was demonstrated for a certain range of utility values.

  3. Adjuvant chemotherapy with sequential or concurrent anthracycline and docetaxel: Breast International Group 02-98 randomized trial

    DEFF Research Database (Denmark)

    Francis, P.; Crown, J.; Di, Leo A.

    2008-01-01

    BACKGROUND: Docetaxel is more effective than doxorubicin for patients with advanced breast cancer. The Breast International Group 02-98 randomized trial tested the effect of incorporating docetaxel into anthracycline-based adjuvant chemotherapy and compared sequential vs concurrent administration....... However, important differences may be related to doxorubicin and docetaxel scheduling, with sequential but not concurrent administration, appearing to produce better DFS than anthracycline-based chemotherapy Udgivelsesdato: 2008/1/16...

  4. Effective treatment of Stage I uterine papillary serous carcinoma with high dose-rate vaginal apex radiation (192Ir) and chemotherapy

    International Nuclear Information System (INIS)

    Turner, Bruce C.; Knisely, Jonathan P. S.; Kacinski, Barry M.; Haffty, Bruce G.; Gumbs, Andrew A.; Roberts, Kenneth B.; Frank, Alex H.; Peschel, Richard E.; Rutherford, Thomas J.; Edraki, Babak; Kohorn, Ernest I.; Chambers, Setsuko K.; Schwartz, Peter E.; Wilson, Lynn D.

    1998-01-01

    Purpose: Uterine papillary serous carcinoma (UPSC) is a morphologically distinct variant of endometrial carcinoma that is associated with a poor prognosis, high recurrence rate, frequent clinical understaging, and poor response to salvage treatment. We retrospectively analyzed local control, actuarial overall survival (OS), actuarial disease-free survival (DFS), salvage rate, and complications for patients with Federation International of Gynecology and Obstetrics (FIGO) (1988) Stage I UPSC. Methods and Materials: This retrospective analysis describes 38 patients with FIGO Stage I UPSC who were treated with the combinations of radiation therapy, chemotherapy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy (TAH/BSO), with or without a surgical staging procedure. Twenty of 38 patients were treated with a combination of low dose-rate (LDR) uterine/vaginal brachytherapy using 226 Ra or 137 Cs and conventional whole-abdomen radiation therapy (WART) or whole-pelvic radiation therapy (WPRT). Of 20 patients (10%) in this treatment group, 2 received cisplatin chemotherapy. Eighteen patients were treated with high dose-rate (HDR) vaginal apex brachytherapy using 192 Ir with an afterloading device and cisplatin, doxorubicin, and cyclophosphamide (CAP) chemotherapy (5 of 18 patients). Only 6 of 20 UPSC patients treated with combination LDR uterine/vaginal brachytherapy and conventional external beam radiotherapy underwent complete surgical staging, consisting of TAH/BSO, pelvic/para-aortic lymph node sampling, omentectomy, and peritoneal fluid analysis, compared to 15 of 18 patients treated with HDR vaginal apex brachytherapy. Results: The 5-year actuarial OS for patients with complete surgical staging and adjuvant radiation/chemotherapy treatment was 100% vs. 61% for patients without complete staging (p = 0.002). The 5-year actuarial OS for all Stage I UPSC patients treated with postoperative HDR vaginal apex brachytherapy and systemic chemotherapy was 94

  5. Sequential radiotherapy and chemotherapy using CDDP and 5-FU for advanced head and neck cancer

    International Nuclear Information System (INIS)

    Takamura, Akio; Arimoto, Takuro; Mizoe, Jun-etsu; Tomita, Masayoshi; Kitahara, Toshihiro; Irie, Goro; Matsuoka, Yoshisuke.

    1991-01-01

    From April 1989 to January 1990, nine patients with locally advanced stage IV squamous cell carcinoma of the head and neck underwent combined chemotherapy and radiotherapy (RT). Chemotherapy consisted of two cycles of CDDP (100 mg/m 2 , day 1) + 5-FU (1 g/m 2 , days 1-5, continuous infusion) every five weeks. RT was interdigitated with chemotherapy after the second course of chemotherapy. Each course was initiated two or three days after interrupting chemotherapy. RT was delivered at 65 or 70 Gy for 8 weeks. Of the 7 patients completing the treatment, 29% responded totally, and 43% responded partially. Seven patients died: two due to acute treatment-related toxicity; four due to locoregional progression; and one due to an unrelated cause. Two patients are still alive (10 and 12 months); one is free of tumor, the other has a metastatic bone tumor. Though sequential use of CT might be considered effective for some patients, acute toxicity was moderate to severe and patients with poor performance (≤70%), elderly (≥70 yr) and renal dysfunction (creatinine clearance<80 ml/min) patients must be considered as high risk for treatment by our combined regimen. (author)

  6. Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors.

    Directory of Open Access Journals (Sweden)

    Young Bae Choi

    Full Text Available We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs. During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant, bacteremia, urinary tract infection (UTI, respiratory virus infection, and varicella zoster virus (VZV reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant, bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection. Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children.

  7. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma. Final results of phase III US Intergroup Trial S9321

    International Nuclear Information System (INIS)

    Kim, Sung-Won; Tobinai, Kensei

    2007-01-01

    The outline of the title trial is described in comparison with outcomes of other randomized controlled trials. The S9321 trial in US started in 1993 by Southwest Oncology Group, Eastern Cooperative Oncology Group and Cancer and Leukemia Group B, including 11 institutions for performance status 0-2 untreated patients of symptomatic multiple myeloma (MM). Patients were randomized to either group receiving the standard dose therapy (SDT) or high-dose therapy with autologous heamatopoietic stem cell transplantation group (HDT). The former essentially underwent the chemotherapy with vincristine, carmustine, melphalan (MEL) and predonisolone after the remission treatment and the latter, whole body irradiation of total 12 Gy (8 fractions/4 days) as well. An appropriate part of the latter group also received the transplantation of allogenic heamatopoietic stem cells previously treated with MEL and 12-Gy radiation. Patients younger than 70 y of age, 899 cases, were registered in the trial, 86 of whom were eliminated before the remission treatment and 248, at that treatment end. No statistical significance was seen between SDT and HDT in efficacy. It is concluded that, despite the present outcome, HDT should be taken into consideration because novel medicals are being under development and MM is a symptomatic disease originated from different molecular bases. (T.I.)

  8. Results of a randomized trial comparing high-dose chemotherapy plus Auto-SCT and R-FC in CLL at diagnosis.

    Science.gov (United States)

    Magni, M; Di Nicola, M; Patti, C; Scimè, R; Mulè, A; Rambaldi, A; Intermesoli, T; Viero, P; Tarella, C; Gueli, A; Bergui, L; Trentin, L; Barzan, A; Benedetti, F; Ambrosetti, A; Di Raimondo, F; Chiarenza, A; Parvis, G; Billio, A; Attolico, I; Olivieri, A; Montanari, M; Carlo-Stella, C; Matteucci, P; Devizzi, L; Guidetti, A; Viviani, S; Valagussa, P; Gianni, A M

    2014-04-01

    The importance of early therapy intensification in B-cell CLL (B-CLL) patients remains to be defined. Even though several studies have been published, no randomized trials comparing directly autologous stem cell transplant (ASCT) and the accepted conventional therapy (that is, rituximab, fludarabine and CY; R-FC) have been reported so far. To assess the benefit of a first-line aggressive therapy, we designed a multicenter, randomized, phase 3 trial comparing R-FC and high-dose chemotherapy supported by ASCT in patients under 65 years of age, with stage B(II) or C B-CLL. Primary end point was CR: 96 patients were enrolled (48 in each arm). On an intent-to-treat basis, the CR rates in the ASCT and R-FC arms were 62.5% and 58%, respectively. After 5 years of follow-up, PFS was 60.4% in the ASCT arm and 65.1% in the R-FC arm, time to progression 65.8 and 70.5%, and overall survival 88% vs 88.1%, respectively. Our trial demonstrates, for the first time in a randomized manner, that frontline ASCT does not translate into a survival advantage when compared with benchmark chemoimmunotherapy in B-CLL patients; the possibility of its clinical benefit in certain subgroups remains uncertain.

  9. Long-term effect of the self-management comprehensive coping strategy program on quality of life in patients with breast cancer treated with high-dose chemotherapy.

    Science.gov (United States)

    Gaston-Johansson, Fannie; Fall-Dickson, Jane M; Nanda, Joy P; Sarenmalm, Elisabeth Kenne; Browall, Maria; Goldstein, Nancy

    2013-03-01

    This study aims to examine the effectiveness of a self-management multimodal comprehensive coping strategy program (CCSP) on quality of life (QOL) among breast cancer patients 1 year after treatment. Patients (n = 110) with stage II, III, or IV breast cancer scheduled to receive high dose chemotherapy and autologous hematopoietic stem cell transplantation were randomized to either CCSP treatment or control group. The CCSP intervention was taught 2 week before hospital admission with reinforcement at specified times during treatment and 3 months after discharge. The CCSP components included educational information, cognitive restructuring, coping skills enhancement, and relaxation with guided imagery. Instruments administered at baseline included the following: Quality of Life Index-Cancer Version (QOLI-CV), State-Trait Anxiety Inventory, Beck Depression Inventory, and Coping Strategies Questionnaire. At 1-year follow-up, patients (n = 73) completed and returned the follow-up QOLI-CV. Patients were mainly ≥ 40 years of age, married, Caucasian, and diagnosed with advanced breast cancer. A model measuring effectiveness of CCSP on QOL (total and subscale) at 1-year follow-up showed that the CCSP group (n = 38) had significant improvement in overall QOL (p psychological/spiritual well-being (p psychological (51%) and sleep problems (60%). The CCSP improved QOL for patients at 1-year follow-up. Patients overwhelmingly reported that CCSP was beneficial. The CCSP as an effective coping intervention has potential as a self-management program for breast cancer survivors. Copyright © 2012 John Wiley & Sons, Ltd.

  10. Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

    Science.gov (United States)

    Krug, L M; Grant, S C; Miller, V A; Ng, K K; Kris, M G

    1999-10-01

    In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

  11. Anti-tumor activity of high-dose EGFR tyrosine kinase inhibitor and sequential docetaxel in wild type EGFR non-small cell lung cancer cell nude mouse xenografts

    Science.gov (United States)

    Tang, Ning; Zhang, Qianqian; Fang, Shu; Han, Xiao; Wang, Zhehai

    2017-01-01

    Treatment of non-small-cell lung cancer (NSCLC) with wild-type epidermal growth factor receptor (EGFR) is still a challenge. This study explored antitumor activity of high-dose icotinib (an EGFR tyrosine kinase inhibitor) plus sequential docetaxel against wild-type EGFR NSCLC cells-generated nude mouse xenografts. Nude mice were subcutaneously injected with wild-type EGFR NSCLC A549 cells and divided into different groups for 3-week treatment. Tumor xenograft volumes were monitored and recorded, and at the end of experiments, tumor xenografts were removed for Western blot and immunohistochemical analyses. Compared to control groups (negative control, regular-dose icotinib [IcoR], high-dose icotinib [IcoH], and docetaxel [DTX]) and regular icotinib dose (60 mg/kg) with docetaxel, treatment of mice with a high-dose (1200 mg/kg) of icotinib plus sequential docetaxel for 3 weeks (IcoH-DTX) had an additive effect on suppression of tumor xenograft size and volume (P Icotinib-containing treatments markedly reduced phosphorylation of EGFR, mitogen activated protein kinase (MAPK), and protein kinase B (Akt), but only the high-dose icotinib-containing treatments showed an additive effect on CD34 inhibition (P icotinib plus docetaxel had a similar effect on mouse weight loss (a common way to measure adverse reactions in mice), compared to the other treatment combinations. The study indicate that the high dose of icotinib plus sequential docetaxel (IcoH-DTX) have an additive effect on suppressing the growth of wild-type EGFR NSCLC cell nude mouse xenografts, possibly through microvessel density reduction. Future clinical trials are needed to confirm the findings of this study. PMID:27852073

  12. Anti-tumor activity of high-dose EGFR tyrosine kinase inhibitor and sequential docetaxel in wild type EGFR non-small cell lung cancer cell nude mouse xenografts

    OpenAIRE

    Tang, Ning; Zhang, Qianqian; Fang, Shu; Han, Xiao; Wang, Zhehai

    2016-01-01

    Treatment of non-small-cell lung cancer (NSCLC) with wild-type epidermal growth factor receptor (EGFR) is still a challenge. This study explored antitumor activity of high-dose icotinib (an EGFR tyrosine kinase inhibitor) plus sequential docetaxel against wild-type EGFR NSCLC cells-generated nude mouse xenografts. Nude mice were subcutaneously injected with wild-type EGFR NSCLC A549 cells and divided into different groups for 3-week treatment. Tumor xenograft volumes were monitored and record...

  13. Final report of Intergroup Trial 0122 (ECOG PE-289, RTOG 90-12): Phase II trial of neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for squamous cell carcinoma of the esophagus

    International Nuclear Information System (INIS)

    Minsky, Bruce D.; Neuberg, Donna; Kelsen, David P.; Pisansky, Thomas M.; Ginsberg, Robert J.; Pajak, Thomas; Salter, Merle; Benson, Al

    1999-01-01

    Purpose: To determine the outcome of neoadjuvant chemotherapy followed by concurrent chemotherapy plus high-dose radiation therapy in patients with local/regional squamous cell carcinoma of the esophagus. Methods and Materials: Forty-five patients with clinical Stage T1-4N0-1M0 squamous cell carcinoma were entered on a prospective single-arm study, of which 38 were eligible. Patients received 3 monthly cycles of 5-FU (1000 mg/m 2 /24 h x 5 days) and cisplatin (100 mg/m 2 day 1; neoadjuvant segment) followed by 2 additional monthly cycles of 5-FU (1000 mg/m 2 /24 h x 5 days) and cisplatin (75 mg/m 2 day 1) plus concurrent 6480 cGy (combined modality segment). The median follow-up in surviving patients was 59 months. Results: For the 38 eligible patients, the primary tumor response rate was 47% complete, 8% partial, and 3% stable disease. The first site of clinical failure was 39% local/regional and 24% distant. For the total patient group, there were 6 deaths during treatment, of which 9% (4/45) were treatment related. The median survival was 20 months. Actuarial survival at 3 years was 30%, and at 5 years, 20%. Conclusion: This intensive neoadjuvant approach does not appear to offer a benefit compared with conventional doses and techniques of combined modality therapy. However, high dose radiation (6480 cGy) appears to be tolerable, and is being tested further in Intergroup Trial INT 0123

  14. Can loco-regional irradiation be a routine supplement to high dose chemotherapy with autologous bone marrow transplant in women with poor prognosis breast cancer

    International Nuclear Information System (INIS)

    Wobeck, Linda K.; Holland, H. Kent; Landry, Jerome C.; Lynn, Michael J.; Hughes, Lorie L.

    1997-01-01

    Purpose: High dose chemotherapy followed by bone marrow transplantation (BMT) is currently being performed in many women with localized, poor prognosis breast cancer. The purpose of this study was to examine patterns of care in radiation treatment as well as acute side effects in women who received breast or chest wall and regional nodal irradiation (XRT) post BMT. Methods: The records of 126 consecutive women with localized, poor prognosis breast cancer who received an autologous BMT at Emory University between (3(90)) and (7(96)) were retrospectively reviewed. Results: All 126 women underwent high dose chemotherapy with cyclophosphamide, carboplatinum and thiotepa followed by BMT. Loco - regional XRT after BMT was routinely recommended for patients with 10 or more positive axillary lymph nodes or inflammatory carcinoma. Overall, 90 patients received local +/- regional XRT; 11 patients prior to BMT and 79 patients post BMT. Three of these patients had a local relapse prior to beginning XRT post BMT. Thirty six patients did not receive XRT for the following reasons: major post BMT morbidity or insufficient hematological recovery (15 patients), less than 10 positive axillary lymph nodes (12 patients), or refusal/not referred (9 patients). Therefore, of the 103 patients (excludes those with less than 10 positive nodes) intended to receive post BMT irradiation, 14.5 % (15 patients- 2 with inflammatory carcinoma) were unable to receive it secondary to post BMT morbidity and 9% (9 patients) refused or were not referred. Of these 79 patients irradiated post BMT, 16 had stage IIA, 20 stage IIB, 27 stage IIIA and 16 inflammatory carcinoma (IIIB). The median time from transplant to irradiation was 82 days (range 44 - 641). Average dose to breast or chest wall was 49.5 Gy (range 42-55.8 Gy). Boost dose (mean 12 Gy, range 10-22 Gy) was given in 62% of patients. The median tumor bed/mastectomy scar dose was 60 Gy (range 42-72 Gy). Supraclavicular, posterior axillary and

  15. Pattern of employment and associated factors in long-term lymphoma survivors 10 years after high-dose chemotherapy with autologous stem cell transplantation.

    Science.gov (United States)

    Kiserud, C E; Fagerli, U-M; Smeland, K B; Fluge, Ø; Bersvendsen, H; Kvaløy, S; Holte, H; Dahl, A A

    2016-05-01

    Background This study examined employment patterns and associated factors in lymphoma survivors treated with high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT) from diagnosis to a follow-up survey at a mean of 10 years after HDT-ASCT. Patients and methods All lymphoma survivors aged ≥18 years at HDT-ASCT in Norway from 1987 to 2008, and alive at the end of 2011 were eligible for this cross-sectional study performed in 2012/2013. Participants completed a mailed questionnaire. Job status was dichotomized as either employed (paid work) or not-employed (disability and retirement pension, on economic support, home-makers, or students). Results The response rate was 78%, and the sample (N = 312) contained 60% men. Mean age at HDT-ASCT was 44.3 and at survey 54.0 years. At diagnosis 85% of survivors were employed, 77% before and 77% after HDT-ASCT, and 58% at follow-up. Forty seven percent of the survivors were employed at all time points. The not-employed group at survey was significantly older and included significantly more females than the employed group. No significant between-group differences were observed for lymphoma-related variables. Fatigue, mental distress and type D personality were significantly higher among those not-employed, while quality of life was significantly lower compared to the employed group. Older age at survey, being female, work ability and presence of type D personality remained significantly related to being not-employed at survey in the multivariable analysis. Conclusions Our findings show that not-employed long-term survivors after HDT-ASCT for lymphoma have more comorbidity, cognitive problems and higher levels of anxiety/depression than employed survivors. These factors should be checked and eventually treated in order to improve work ability.

  16. Breast conserving treatment of locally advanced carcinoma T2 and T3 after neoadjuvant chemotherapy followed by quadrantectomy and high dose-rate brachytherapy, as a boost, complementary teletherapy and adjuvant chemotherapy

    International Nuclear Information System (INIS)

    Fristachi, Carlos Elias

    2005-01-01

    Objective: to assess the treatment of breast cancer T2 and T3(T > = 4 cm), through neoadjuvant chemotherapy, quadrantectomy and high-dose-rate (HDR) brachytherapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering its method problems, its esthetics results, the aspect of local control, overall survival, and disease-free survival. Patients and method: this clinical prospective descriptive study was based on the evaluation of 26 patients ranging from 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIB and IIIA, responsive to the neoadjuvant chemotherapy. Early and late radiotherapy complications were evaluated according to the criteria established by the RTOG/EORTC (Radiotherapy and Oncology Group /European Organization for Research and Treatment of Cancer) groups. Esthetics evaluation was done in accordance with the criteria set by a plastic surgeon. Local control was evaluated by clinical method, mammography and ultrasonography. Overall survival (OS) and the disease-free survival (DFS) were assessed according to Kaplan-Meier methodology. All the patients were treated at the Dr. Arnaldo Vieira de Carvalho Cancer Institute, from June/1995 to November/2001, and evaluated in March, 2002, with median follow-up of 28.7 months. Results: early complications were observed in 8 patients (30.6%). Two patients were classified as G3 and G4 (RTOG/EORTC). Six patients had late complications and three of them (11.5%) were classified as G3 and G4. One patient (3.8%) had local recurrence, 64 months after having local treatment. Esthetics results were considered good or regular in 16 patients (60.5%) out of 24 patients who were examined. Overall survival and disease-free survival in 24, 36 and 60 months were 100%, 92.3% and 83.1% respectively. Conclusion: early and late radiotherapy complications were considerate high when compared to literature, but esthetic results were considered acceptable. RL, OS and DFS were comparable to other

  17. Early and late toxicity of involved-field radiation therapy in conjunction with high-dose chemotherapy and stem cell rescue

    International Nuclear Information System (INIS)

    Lubich, L.; Mundt, A.; Sibley, G.; Hallahan, D.; Nautiyal, J.; Weichselbaum, R.

    1995-01-01

    Purpose: Recent reports have demonstrated a benefit to involved-field radiation therapy (IFRT) in patients with relapsed/metastatic disease undergoing high-dose chemotherapy (HDCT) and stem cell rescue (SCR). We evaluate here the early and late toxicity of this approach. Methods: Eighty-five patients with either metastatic breast cancer (MBC) (31) or relapsed/refractory Hodgkin's disease (HD) (54) underwent HDCT/SCR. HDCT in the MBC patients consisted of cytoxan, thiotepa +/- carmustine and VP-16, cytoxan, BCNU +/- thiotepa in the HD patients. Thirty-four patients (40%) received IFRT either prior to (14) or following (20) HDCT to sites of disease involvement. A total of 18 patients received chest wall/mediastinal (CWMED) RT. Median followup for the MBC and HD patients were 21.3 months and 41 months, respectively. Results: Acute sequelae were similar in the 2 groups. Only one patient (5%) treated with IFRT (HD with 5 nodal sites) required a break from therapy due to low blood counts. Seven patients (0 MBC, 7 HD) (8.2%) suffered a toxic death (TD). No difference in was seen in the rate of TD in the patients as a whole ((1(14)) vs. (6(71))) (p =0.87) nor in the HD patients alone ((1(7)) vs. (6(47))) (p =0.91) with the use of IFRT prior to HDCT. Eleven patients (12.9%) developed late toxicity: 3 myelodysplasia/acute leukemia (MAL), 2 persistent low blood counts (requiring transfusions), 4 pulmonary toxicity (PT) and 2 hypothyroidism. All 4 cases of PT occurred in the HD group of which 3 received CWMED RT. The Table below shows the 5-yr actuarial risk of PT with and without CWMED RT as well as the 5-yr actuarial risk of MAL and any hematologic sequelae with and without RT. Multivariate analysis in the HD patients demonstrated that CWMED RT was the most significant factor for PT (p =0.09). All 3 cases of MAL and the 2 cases of persistent low blood counts occurred in the HD group. The use of IFRT did not increase the incidence of MAL or of any hematologic sequelae

  18. A Contralateral Esophagus-Sparing Technique to Limit Severe Esophagitis Associated With Concurrent High-Dose Radiation and Chemotherapy in Patients With Thoracic Malignancies

    International Nuclear Information System (INIS)

    Al-Halabi, Hani; Paetzold, Peter; Sharp, Gregory C.; Olsen, Christine; Willers, Henning

    2015-01-01

    Purpose: Severe (Radiation Therapy Oncology Group [RTOG] grade 3 or greater) esophagitis generally occurs in 15% to 25% of non–small cell lung cancer (NSCLC) patients undergoing concurrent chemotherapy and radiation therapy (CCRT), which may result in treatment breaks that compromise local tumor control and pose a barrier to dose escalation. Here, we report a novel contralateral esophagus-sparing technique (CEST) that uses intensity modulated radiation therapy (IMRT) to reduce the incidence of severe esophagitis. Methods and Materials: We reviewed consecutive patients with thoracic malignancies undergoing curative CCRT in whom CEST was used. The esophageal wall contralateral (CE) to the tumor was contoured as an avoidance structure, and IMRT was used to guide a rapid dose falloff gradient beyond the target volume in close proximity to the esophagus. Esophagitis was recorded based on the RTOG acute toxicity grading system. Results: We identified 20 consecutive patients treated with CCRT of at least 63 Gy in whom there was gross tumor within 1 cm of the esophagus. The median radiation dose was 70.2 Gy (range, 63-72.15 Gy). In all patients, ≥99% of the planning and internal target volumes was covered by ≥90% and 100% of prescription dose, respectively. Strikingly, no patient experienced grade ≥3 esophagitis (95% confidence limits, 0%-16%) despite the high total doses delivered. The median maximum dose, V45, and V55 of the CE were 60.7 Gy, 2.1 cc, and 0.4 cc, respectively, indicating effective esophagus cross-section sparing by CEST. Conclusion: We report a simple yet effective method to avoid exposing the entire esophagus cross-section to high doses. By using proposed CE dose constraints of V45 <2.5 cc and V55 <0.5 cc, CEST may improve the esophagus toxicity profile in thoracic cancer patients receiving CCRT even at doses above the standard 60- to 63-Gy levels. Prospective testing of CEST is warranted

  19. A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974)

    DEFF Research Database (Denmark)

    Daugaard, G; Skoneczna, I; Aass, N

    2011-01-01

    To compare the efficacy of one cycle of standard dose cisplatin, etoposide, and ifosfamide (VIP) plus three cycles of high-dose VIP followed by stem-cell infusion [high-dose chemotherapy (HD-CT arm)] to four cycles of standard cisplatin, etoposide, and bleomycin (BEP) in patients with poor-progno...

  20. Twenty-five year outcome of sequential abdominopelvic radiotherapy and alkylating agent chemotherapy for ovarian carcinoma

    International Nuclear Information System (INIS)

    Bellairs, Ellen E.; Twiggs, Leo B.; Potish, Roger A.

    1997-01-01

    Purpose: A prospective study of sequential surgery, abdominopelvic radiotherapy and single agent alkylating chemotherapy was conducted to evaluate survival and toxicity in the management of ovarian carcinoma. Methods: From 1970-1976, 95 women with stage I-III epithelial ovarian carcinoma were scheduled to receive postoperative radiotherapy consisting of 20.0 Gy to the whole abdomen (1.0 Gy/day), a 29.75 Gy pelvic boost (1.75 Gy/day) and 10 subsequent courses of Melphalan (1 mg/kg/course). Endpoints were overall survival, disease-free survival(DFS), and acute and chronic toxicity. Results: The evaluable 94 patients included 19 stage I, 25 stage II, and 50 stage III. Of the latter, 21 had no palpable disease postoperatively (IIIN) and 29 had postoperative palpable disease (IIIP). Overall survival at 5, 10, 15 and 20 years was 42%, 30%, 23% and 22%. DFS for the entire group was 54% at 5 years and remained 50% from 10 to 25 years. All but two recurrences were noted within the first 27 months. No recurrence or treatment-related deaths occurred after 8 years. After 10 years, the survival of the study group became parallel to the general population. Prognostic factors were only related to stage (p<.001) and the presence of postoperative palpable disease(p<.001). DFS at 25 years was 95 % for stage I, 71% at 5 years and 66% from 10 to 25 years for stage II, and 17% at 5 years and 11% thereafter for stage III patients(p<.001). Although no stage IIIP patients were cured, 25% lived beyond 2 years. Five year DFS was significantly better in IIIN (45%) vs. IIIP (0%) patients (p<.001). The 65 patients without postoperative palpable disease, (stage I-IIIN) achieved DFS at 5 and 25 years of 69%, and 61%, respectively. Of 31 patients undergoing a second-look surgery, 84% were found to be free of tumor. Two recurred at 3.5 and 7 years after surgery. Acute tolerance was acceptable. Chronic toxicity included an 11.7% rate of small bowel obstruction requiring surgery and a 3% rate of

  1. Comparison of low and high dose rate brachytherapy in the treatment of uterine cervix cancer. Retrospective analysis of two sequential series

    International Nuclear Information System (INIS)

    Ferrigno, Robson; Nishimoto, Ines Nobuko; Ribeiro dos Santos Novaes, Paulo Eduardo; Pellizzon, Antonio Cassio Assis; Conte Maia, Maria Aparecida; Fogarolli, Ricardo Cesar; Salvajoli, Joao Victor

    2005-01-01

    Purpose: This retrospective analysis aims to report on the comparative outcome of cervical cancer patients treated with low dose rate (LDR) and high dose rate (HDR) brachytherapy. Methods and Materials: From 1989 to 1995, 190 patients were treated with low dose rate (LDR) brachytherapy (LDR group) and from 1994 to 2001, 118 patients were treated with high dose rate (HDR) brachytherapy (HDR group). FIGO stage distribution for the LDR group was Stage I: 6.3%; Stage II: 57.4%; and Stage III: 36.3% and for the HDR group Stage I: 9.3%; Stage II: 43.2%; and Stage III: 47.4%. All patients were treated with telecobalt external-beam radiotherapy (EBR). Median doses of LDR brachytherapy at Point A were 40 Gy and 50 Gy for patients treated with 1 and 2 implants, respectively. All patients from the HDR group were treated with 24 Gy in 4 fractions of 6 Gy to Point A. Survival, disease-free survival, local control, and late complications at 5 years, were endpoints compared for both groups. Results: Median follow-up time for LDR and HDR groups was 70 months (range, 8-127 months) and 33 months (range, 4-117 months), respectively. For all stages combined, overall survival, disease-free survival, and local control at 5 years were better in the LDR group (69% vs. 55%, p = 0.007; 73% vs. 56%, p = 0.002; and 74% vs. 65%; p = 0.04, respectively). For clinical Stages I and II, no differences was seen in overall survival, disease-free survival, and local control at 5 years between the two groups. For clinical Stage III, overall survival and disease-free survival at 5 years were better in the LDR group than in the HDR group (46% vs. 36%, p = 0.04 and 49% vs. 37%, p = 0.03, respectively), and local control was marginally higher in the LDR group than in the HDR group (58% vs. 50%, p = 0.19). The 5-year probability of rectal complications was higher in the LDR group than in the HDR group (16% vs. 8%, p = 0.03) and 5-year probability of small bowel and urinary complications was not

  2. Early lymphocyte recovery after intensive timed sequential chemotherapy for acute myelogenous leukemia: peripheral oligoclonal expansion of regulatory T cells.

    Science.gov (United States)

    Kanakry, Christopher G; Hess, Allan D; Gocke, Christopher D; Thoburn, Christopher; Kos, Ferdynand; Meyer, Christian; Briel, Janet; Luznik, Leo; Smith, B Douglas; Levitsky, Hyam; Karp, Judith E

    2011-01-13

    Few published studies characterize early lymphocyte recovery after intensive chemotherapy for acute myelogenous leukemia (AML). To test the hypothesis that lymphocyte recovery mirrors ontogeny, we characterized early lymphocyte recovery in 20 consecutive patients undergoing induction timed sequential chemotherapy for newly diagnosed AML. Recovering T lymphocytes were predominantly CD4(+) and included a greatly expanded population of CD3(+)CD4(+)CD25(+)Foxp3(+) T cells. Recovering CD3(+)CD4(+)CD25(+)Foxp3(+) T cells were phenotypically activated regulatory T cells and showed suppressive activity on cytokine production in a mixed lymphocyte reaction. Despite an initial burst of thymopoiesis, most recovering regulatory T cells were peripherally derived. Furthermore, regulatory T cells showed marked oligoclonal skewing, suggesting that their peripheral expansion was antigen-driven. Overall, lymphocyte recovery after chemotherapy differs from ontogeny, specifically identifying a peripherally expanded oligoclonal population of activated regulatory T lymphocytes. These differences suggest a stereotyped immunologic recovery shared by patients with newly diagnosed AML after induction timed sequential chemotherapy. Further insight into this oligoclonal regulatory T-cell population will be fundamental toward developing effective immunomodulatory techniques to improve survival for patients with AML.

  3. Tamoxifen effects on subjective and psychosexual well-being, in a randomised breast cancer study comparing high-dose and standard-dose chemotherapy

    NARCIS (Netherlands)

    Mourits, MJ; Bockermann, [No Value; de Vries, EG; van der Zee, AG; ten Hoor, KA; van der Graaf, WT; Sluiter, WJ; Willemse, PH

    2002-01-01

    To evaluate the impact of tamoxifen on subjective and psychosexual well-being in breast cancer patients in relation to type of prior chemotherapy and menopausal status. Longitudinal interview study in breast cancer patients during and after adjuvant tamoxifen use. Menopausal status was defined by

  4. High-dose rapid and standard induction chemotherapy for patients aged over 1 year with stage 4 neuroblastoma: a randomised trial.

    Science.gov (United States)

    Pearson, Andrew D J; Pinkerton, C Ross; Lewis, Ian J; Imeson, John; Ellershaw, Caroline; Machin, David

    2008-03-01

    The current standard treatment for patients with high-risk neuroblastoma includes initial induction chemotherapy with a 21-day interval between induction treatments. We aimed to assess whether an intensive chemotherapy protocol that had a 10-day interval between treatments would improve event-free survival (EFS) in patients aged 1 year or over with high-risk neuroblastoma. Between Oct 30, 1990, and March 18, 1999, patients with stage 4 neuroblastoma who had not received previous chemotherapy were enrolled from 29 centres in Europe. Patients were randomly assigned to rapid treatment (cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C], known as COJEC) or standard treatment (vincristine [O], cisplatin [P], etoposide [E], and cyclophosphamide [C], ie, OPEC, alternated with vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C], ie, OJEC). Both regimens used the same total cumulative doses of each drug (except vincristine), but the dose intensity of the rapid regimen was 1.8-times higher than that of the standard regimen. The standard regimen was given every 21 days if patients showed haematological recovery, whereas the rapid regimen was given every 10 days irrespective of haematological recovery. Response to chemotherapy was assessed according to the conventional International Neuroblastoma Response Criteria (INRC). In responders, surgical excision of the primary tumour was attempted, followed by myeloablation (with 200 mg/m2 of melphalan) and haemopoietic stem-cell rescue. Primary endpoints were 3-year, 5-year, and 10-year EFS. Data were analysed by intention to treat. This trial is registered on the clinical trials site of the US National Cancer Institute website, number NCT00365755, and also as EU-20592 and CCLG-NB-1990-11. 262 patients, of median age 2.95 years (range 1.03-20.97), were randomly assigned-132 patients to standard and 130 patients to rapid treatment. 111 patients in the standard group and 109

  5. Non-cross resistant sequential single agent chemotherapy in first-line advanced non-small cell lung cancer patients: Results of a phase II study

    NARCIS (Netherlands)

    V. Surmont; J.G.J.V. Aerts (Joachim); K.Y. Tan; F.M.N.H. Schramel (Franz); R. Vernhout (Rene); H.C. Hoogsteden (Henk); R.J. van Klaveren (Rob)

    2009-01-01

    textabstractBackground. sequential chemotherapy can maintain dose intensity and preclude cumulative toxicity by increasing drug diversity. Purpose. to investigate the toxicity and efficacy of the sequential regimen of gemcitabine followed by paclitaxel in first line advanced stage non-small cell

  6. High-dose chemotherapy and immunotherapy in adult Burkitt lymphoma: comparison of results in human immunodeficiency virus-infected and noninfected patients.

    Science.gov (United States)

    Oriol, Albert; Ribera, Josep-Maria; Bergua, Juan; Giménez Mesa, Eduardo; Grande, Carlos; Esteve, Jordi; Brunet, Salut; Moreno, Maria-Jose; Escoda, Lourdes; Hernandez-Rivas, Jesus-Maria; Hoelzer, Dieter

    2008-07-01

    It has been recognized that cure is possible for human immunodeficiency virus (HIV)-infected patients with Burkitt lymphoma/leukemia (BL) if appropriate chemotherapy is used. The introduction of rituximab in BL therapeutic schemes has been scarcely explored. The outcome and toxicity of HIV-positive patients with BL treated in a rituximab and intensive chemotherapy-based trial was evaluated. Thirty-six consecutive patients, 15 to 55 years of age, diagnosed with advanced stage BL were recruited from July 2003 to August 2006, stratified according to HIV infection status and treated with 6 cycles of intensive chemotherapy including 8 doses of rituximab. Nineteen of the patients (53%) were HIV-infected. Their clinical characteristics were comparable to those of the HIV-negative patients. Complete remission (CR) rates were 88% and 84%, respectively, for HIV-negative and -positive patients. Twenty-seven patients (82% and 68%, respectively, for HIV-negative and -positive patients) completed the 6 protocol scheduled cycles. HIV-infected patients presented higher incidences of grade 3-4 mucositis (27% vs 7% of cycles, P = .0005) and severe infectious episodes (26% vs 8%, P = .0025). However, there were no statistically significant differences in 2-year overall survival (82%, 95% confidence interval [CI], 65%-99% and 73%, 95% CI, 54%-92%, respectively) or 2-year disease-free survival (93%, 95% CI, 82%-99% and 87%, 95% CI 72%-99%, respectively). Intensive immunochemotherapy can be administered safely to patients with HIV infection. Despite a higher incidence of severe mucositis and infections the remission and survival rates are comparable to those observed in HIV-negative patients. (Copyright) 2008 American Cancer Society.

  7. Effects of intensive induction and consolidation chemotherapy with idarubicin and high dose cytarabine on minimal residual disease levels in newly diagnosed adult precursor-B acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Kenneth F. Bradstock

    2016-12-01

    Full Text Available An intensive induction regimen, consisting of idarubicin and high dose cytarabine, was assessed in 19 adult patients, median age 44 years, with newly diagnosed precursor-B acute lymphoblastic leukemia (ALL. Patients achieving a complete response (CR were given an attenuated consolidation course. The primary endpoints were induction death rate and incidence of serious non-hematological toxicity. Grades 3–4 diarrhoea occurred in 47% of patients during induction. Two patients (11% died during induction therapy, and 2 were withdrawn due to resistant disease or prolonged marrow hypoplasia. Fifteen patients achieved CR (79%, but levels of minimal residual disease (MRD after induction were comparable with those previously observed using a modified pediatric protocol. Overall survival at 5 years was 36.8% while leukemia-free survival was 44.1%. An intensive AML protocol used in adults with ALL resulted in substantial toxicity and provided similar levels of cytoreduction to conventional ALL protocols, without improving long-term outcomes.

  8. Feasibility Study of Sequentially Alternating EGFR-TKIs and Chemotherapy for Patients with Non-small Cell Lung Cancer.

    Science.gov (United States)

    Takemura, Yoshizumi; Chihara, Yusuke; Morimoto, Yoshie; Tanimura, Keiko; Imabayashi, Tatsuya; Seko, Yurie; Kaneko, Yoshiko; Date, Koji; Ueda, Mikio; Arimoto, Taichiro; Iwasaki, Yoshinobu; Takayama, Koichi

    2018-04-01

    The purpose of this trial was to evaluate the feasibility and efficacy of alternating platinum-based doublet chemotherapy with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant non-small cell lung cancer (NSCLC). Chemotherapy-naive patients with advanced NSCLC harboring an EGFR mutation were enrolled. All patients underwent induction chemotherapy by sequentially alternating pemetrexed/cisplatin/bevacizumab and EGFR-TKIs followed by maintenance therapy with pemetrexed/bevacizumab and EGFR-TKIs. The primary outcome was the completion rate of the induction therapy. Eighteen eligible patients were enrolled between May 2011 and March 2016. The completion rate of induction therapy was 72.2% (13/18). Unfortunately, one patient developed grade 4 acute renal injury, but no other serious complications concerning this protocol were observed. Furthermore, diarrhea, rashes, and hematological adverse effects were mild. The completion rate of induction therapy was promising. Alternating chemotherapy and EGFR-TKIs should be further investigated regarding feasibility and efficacy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Timed sequential chemotherapy of cytoxan-refractory multiple myeloma with cytoxan and adriamycin based on induced tumor proliferation.

    Science.gov (United States)

    Karp, J E; Humphrey, R L; Burke, P J

    1981-03-01

    Malignant plasma cell proliferation and induced humoral stimulatory activity (HSA) occur in vivo at a predictable time following drug administration. Sequential sera from 11 patients with poor-risk multiple myeloma (MM) undergoing treatment with Cytoxan (CY) 2400 mq/sq m were assayed for their in vitro effects on malignant bone marrow plasma cell tritiated thymidine (3HTdR) incorporation. Peak HSA was detected day 9 following CY. Sequential changes in marrow malignant plasma cell 3HTdR-labeling indices (LI) paralleled changes in serum activity, with peak LI occurring at the time of peak HS. An in vitro model of chemotherapy demonstrated that malignant plasma cell proliferation was enhanced by HSA, as determined by 3HTdR incorporation assay, 3HTdR LI, and tumor cells counts, and that stimulated plasma cells were more sensitive to cytotoxic effects of adriamycin (ADR) than were cells cultured in autologous pretreatment serum. Based on these studies, we designed a clinical trial to treat 12 CY-refractory poor-risk patients with MM in which ADR (60 mg/sq m) was administered at the time of peak HSA and residual tumor cell LI (day 9) following initial CY, 2400 mg/m (CY1ADR9). Eight of 12 (67%) responded to timed sequential chemotherapy with a greater than 50% decrement in monoclonal protein marker and a median survival projected to be greater than 8 mo duration (range 4-21+ mo). These clinical results using timed sequential CY1ADR9 compare favorably with results obtained using ADR in nonsequential chemotherapeutic regimens.

  10. Serum creatinine and creatinine clearance for predicting plasma methotrexate concentrations after high-dose methotrexate chemotherapy for the treatment for childhood lymphoblastic malignancies.

    Science.gov (United States)

    Xu, Wei-qun; Zhang, Ling-yan; Chen, Xue-ying; Pan, Bin-hua; Mao, Jun-qing; Song, Hua; Li, Jing-yuang; Tang, Yong-min

    2014-01-01

    Monitoring of plasma methotrexate (MTX) concentrations allows for therapeutic adjustments in treating childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) with high-dose MTX (HDMTX). We tested the hypothesis that assessment of creatinine clearance (CrCl) and/or serum Cr may be a suitable means of monitoring plasma MTX concentrations. All children in the study had ALL or NHL, were in complete remission, and received HDMTX (3 or 5 g/m(2))+leucovorin. Plasma MTX concentrations were measured at 24, 48, and 96 h. CrCl was determined at 24 and 48 h. Correlations between 24- and 48-h plasma MTX concentrations and CrCl and serum Cr concentrations were determined. CrCl and serum Cr concentrations were compared over time between children who had delayed and non-delayed MTX elimination. A total of 105 children were included. There were significant negative correlations between CrCl at 24 and 48 h and plasma MTX concentrations at 24 (both p < 0.001) and 48 h (both p < 0.001). There were significant positive correlations between serum Cr concentrations at both 24 and 48 h and plasma MTX concentrations at 24 (both p < 0.001) and 48 h (both p < 0.001). There were 88 (30.2 %) instances of elimination delay. Children with elimination delay had significantly lower CrCl and higher Cr concentrations at 24 and 48 h compared with children without elimination delay (all p < 0.05). Our findings suggest that, with further refinement, assessment of renal function may be a useful means of monitoring plasma MTX concentrations during HDMTX for ALL and NHL.

  11. γ-Herpesvirus load as surrogate marker of early death in HIV-1 lymphoma patients submitted to high dose chemotherapy and autologous peripheral blood stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Chiara Pratesi

    Full Text Available Autologous stem cell transplantation (ASCT is a feasible procedure for human immunodeficiency virus-1 (HIV-1 lymphoma patients, whose underlying disease and intrinsic HIV-1- and ASCT-associated immunodeficiency might increase the risk for γ-herpesvirus load persistence and/or reactivation. We evaluated this hypothesis by investigating the levels of Epstein-Barr virus (EBV- and Kaposi sarcoma-associated herpesvirus (KSHV-DNA levels in the peripheral blood of 22 HIV-1-associated lymphoma patients during ASCT, highlighting their relationship with γ-herpesvirus lymphoma status, immunological parameters, and clinical events. EBV-DNA was detected in the pre-treatment plasma and peripheral blood mononuclear cells (PBMCs of 12 (median 12,135 copies/mL and 18 patients (median 417 copies/10(6 PBMCs, respectively; the values in the two compartments were correlated (r = 0.77, p = 0.0001. Only EBV-positive lymphomas showed detectable levels of plasma EBV-DNA. After debulking chemotherapy, plasma EBV-DNA was associated with lymphoma chemosensitivity (p = 0.03 and a significant higher mortality risk by multivariate Cox analysis adjusted for EBV-lymphoma status (HR, 10.46, 95% CI, 1.11-98.32, p = 0.04. After infusion, EBV-DNA was detectable in five EBV-positive lymphoma patients who died within six months. KSHV-DNA load was positive in only one patient, who died from primary effusion lymphoma. Fluctuations in levels of KSHV-DNA reflected the patient's therapy and evolution of his underlying lymphoma. Other γ-herpesvirus-associated malignancies, such as multicentric Castleman disease and Kaposi sarcoma, or end-organ complications after salvage treatment were not found. Overall, these findings suggest a prognostic and predictive value of EBV-DNA and KSHV-DNA, the monitoring of which could be a simple, complementary tool for the management of γ-herpesvirus-positive lymphomas in HIV-1 patients submitted to ASCT.

  12. Prevalence of menstrual cycles and outcome of 50 pregnancies after high-dose chemotherapy and auto-SCT in non-Hodgkin and Hodgkin lymphoma patients younger than 40 years.

    Science.gov (United States)

    Akhtar, S; Youssef, I; Soudy, H; Elhassan, T A M; Rauf, S M; Maghfoor, I

    2015-12-01

    Data are limited regarding the prevalence of menstrual cycles and pregnancies after high-dose chemotherapy (HDC) and auto-stem cell transplantation (SCT). Female patients who underwent HDC auto-SCT for non-Hodgkin and Hodgkin lymphoma (1997-2012) were reviewed. The selection criteria were as follows: (1) alive without disease 12 and 24 months after auto-SCT for menstrual cycles and pregnancy, respectively, (2) age SCT, and (3) no primary infertility. One-hundred and seventy-six females underwent single auto-SCT. Eighty-nine were eligible for menstrual cycles and pregnancy analysis. Median age at auto-SCT was 25 years (14-40 years), at pregnancy 27 years (20-37 years), median follow-up 65 months (range 24-190). Regular menstrual-cycles resumed in 56/89 patients (63%). Increasing age (P=0.02) and number of prior chemotherapy cycles (P=0.02) are associated with higher risk of amenorrhea. Forty patients tried to get pregnant, 26 (65%) became pregnant 50 times: 43 (86%) live birth, 7 (14%) miscarriage and 2/50 had birth defects. Twenty-four patients practiced breastfeeding (median duration 4 months (1-24 months)). Enough breast milk production was reported 62.5% vs 100% in those patients who did or did not receive above the diaphragm radiation therapy, respectively, (P=0.066). Our data highlights significantly higher than perceived incidence of menstrual cycle resumption, successful pregnancies and breastfeeding after HDC auto-SCT.

  13. Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial.

    Science.gov (United States)

    Ladenstein, Ruth; Pötschger, Ulrike; Pearson, Andrew D J; Brock, Penelope; Luksch, Roberto; Castel, Victoria; Yaniv, Isaac; Papadakis, Vassilios; Laureys, Geneviève; Malis, Josef; Balwierz, Walentyna; Ruud, Ellen; Kogner, Per; Schroeder, Henrik; de Lacerda, Ana Forjaz; Beck-Popovic, Maja; Bician, Pavel; Garami, Miklós; Trahair, Toby; Canete, Adela; Ambros, Peter F; Holmes, Keith; Gaze, Mark; Schreier, Günter; Garaventa, Alberto; Vassal, Gilles; Michon, Jean; Valteau-Couanet, Dominique

    2017-04-01

    High-dose chemotherapy with haemopoietic stem-cell rescue improves event-free survival in patients with high-risk neuroblastoma; however, which regimen has the greatest patient benefit has not been established. We aimed to assess event-free survival after high-dose chemotherapy with busulfan and melphalan compared with carboplatin, etoposide, and melphalan. We did an international, randomised, multi-arm, open-label, phase 3 cooperative group clinical trial of patients with high-risk neuroblastoma at 128 institutions in 18 countries that included an open-label randomised arm in which high-dose chemotherapy regimens were compared. Patients (age 1-20 years) with neuroblastoma were eligible to be randomly assigned if they had completed a multidrug induction regimen (cisplatin, carboplatin, cyclophosphamide, vincristine, and etoposide with or without topotecan, vincristine, and doxorubicin) and achieved an adequate disease response. Patients were randomly assigned (1:1) to busulfan and melphalan or to carboplatin, etoposide, and melphalan by minimisation, balancing age at diagnosis, stage, MYCN amplification, and national cooperative clinical group between groups. The busulfan and melphalan regimen comprised oral busulfan (150 mg/m 2 given on 4 days consecutively in four equal doses); after Nov 8, 2007, intravenous busulfan was given (0·8-1·2 mg/kg per dose for 16 doses according to patient weight). After 24 h, an intravenous melphalan dose (140 mg/m 2 ) was given. Doses of busulfan and melphalan were modified according to bodyweight. The carboplatin, etoposide, and melphalan regimen consisted of carboplatin continuous infusion of area under the plasma concentration-time curve 4·1 mg/mL per min per day for 4 days, etoposide continuous infusion of 338 mg/m 2 per day for 4 days, and melphalan 70 mg/m 2 per day for 3 days, with doses for all three drugs modified according to bodyweight and glomerular filtration rate. Stem-cell rescue was given after the last dose of

  14. Sequential transurethral surgery, multiple drug chemotherapy and radiation therapy for invasive bladder carcinoma: Initial report

    International Nuclear Information System (INIS)

    Cervek, J.; Cufer, T.; Kragelj, B.; Zakotnik, B.; Stanonik, M.

    1993-01-01

    Forty-seven patients with muscle-invasive bladder cancer (T2--T4, Nx, MO) were treated by transurethral resection, followed by 3--4 cycles of combination chemotherapy (methothrexate 30 mg/m2 on days 1, 14; cis-platinum 100 mg/m2 on day 2; vinblastine 3 mg/m2 on days 1, 14; repeated every 21 days), and external beam irradiation (64--66 Gy to the bladder and 40 Gy to the pelvic lymphatics). Complete remission after transurethral resection and chemotherapy was achieved in 24 out of 45 patients (53%). Cystectomy was performed in patients without complete response to transurethral resection and chemotherapy. The therapy was completed as planned in 45/47 patients. After transurethral resection, chemotherapy, and radiation therapy, biopsy proven complete response was achieved in 62% (28/45); Stage T2T3 in 67% (23/24), Stage T4 in 45% (5/11) of patients. Among 19 patients with positive biopsy findings after transurethral resection and chemotherapy, 14 underwent cystectomy. After follow-up of 4--55 months (median 23 months) 75% (34/45) are alive, 68% (31/45) have had their bladders preserved, and 53% (24/45) are free of the primary tumor. The actuarial survival of all 45 patients is 73%. Moderate nausea and vomiting during treatment were common; severe leukopenia and mucositis were observed in five patients. Late side effects such as miction disorders and diarrhea were predominantly mild. Although the observation period has been too short to allow a definitive evaluation of treatment results, the authors feel both from the point of bladder preservation and disease-free survival that the presented treatment approach is successful in a majority of T2T3 patients, whereas a large tumor size (T4) renders this treatment less effective. 17 refs., 4 figs., 4 tabs

  15. The use of a sequential high dose recombinant interleukin 2 regimen after autologous bone marrow transplantation does not improve the disease free survival of patients with acute leukemia transplanted in first complete remission.

    Science.gov (United States)

    Blaise, D; Attal, M; Pico, J L; Reiffers, J; Stoppa, A M; Bellanger, C; Molina, L; Nedellec, G; Vernant, J P; Legros, M; Gabus, R; Huguet, F; Brandely, M; Hercend, T; Olive, D; Maraninchi, D

    1997-05-01

    We report the outcome of 50 consecutive patients with CR1 acute leukemia (AML = 22; ALL = 28) treated with autologous BMT, after cyclophosphamide and TBI, followed with a sequential high dose rIL2 regimen. rIL-2 (RU 49637 from Roussel-Uclaf, Romainville, France) was started after hematological reconstitution an average of 72 +/- 22 days post transplant. The schedule consisted of a continuous infusion over 5 cycles (Cycle 1: 5 days starting on day 1; cycle 2-5: 2 days starting on day 15, 29, 43 and 57). Patients were treated at 4 different dosages (12 (N = 40), 16 (N = 3), 20 (N = 2), 24 (N = 5) x 10(6) IU/m2/day). Toxicities were mainly related to capillary leak syndrome and thrombocytopenia. Patients received an average of 122 +/- 49 10(6) IU/m2. Two patients with AML died from toxicity. rIL-2 infusion was associated with very a high level of immune stimu-lation of both T-cells (P < 0.05) and natural killer (NK) cells (P < 0.05) and associated cytolytic functions (P < 0.05). With a minimal and median follow-up of 21 and 46 months, 3 year leukemia free survival is 41 +/- 6% overall, 39 +/- 10% and 43 +/- 8% for AML and ALL respectively. Relapse probabilities at 3 years are 59 +/- 11% for AML and 57 +/- 8% for ALL. We conclude that this short infusion of rIL-2 over 2 months, resulting in an increased immune stimulation, is not associated with a better leukemic control for patients with acute leukemia transplanted early after reaching first complete remission.

  16. Chemotherapy

    Science.gov (United States)

    ... nurse can help you balance the risks of chemotherapy against the potential benefits. It is important to note that the information provided here is basic and does not take the place of professional advice. If you have any questions ... Publication Quimioterapia (Chemotherapy) Una publicación de ...

  17. Concurrent and sequential initiation of ovarian function suppression with chemotherapy in premenopausal women with endocrine-responsive early breast cancer: an exploratory analysis of TEXT and SOFT.

    Science.gov (United States)

    Regan, M M; Walley, B A; Francis, P A; Fleming, G F; Láng, I; Gómez, H L; Colleoni, M; Tondini, C; Pinotti, G; Salim, M; Spazzapan, S; Parmar, V; Ruhstaller, T; Abdi, E A; Gelber, R D; Coates, A S; Goldhirsch, A; Pagani, O

    2017-09-01

    Recent breast cancer treatment guidelines recommend that higher-risk premenopausal patients should receive ovarian function suppression (OFS) as part of adjuvant endocrine therapy. If chemotherapy is also given, it is uncertain whether to select concurrent or sequential OFS initiation. We analyzed 1872 patients enrolled in the randomized phase III TEXT and SOFT trials who received adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer and upon randomization to an OFS-containing adjuvant endocrine therapy, initiated gonadotropin-releasing-hormone-agonist triptorelin. Breast cancer-free interval (BCFI) was compared between patients who received OFS concurrently with chemotherapy in TEXT (n = 1242) versus sequentially post-chemotherapy in SOFT (n = 630). Because timing of trial enrollment relative to adjuvant chemotherapy differed, we implemented landmark analysis re-defining BCFI beginning 1 year after final dose of chemotherapy (median, 15.5 and 8.1 months from enrollment to landmark in TEXT and SOFT, respectively). As a non-randomized treatment comparison, we implemented comparative-effectiveness propensity score methodology with weighted Cox modeling. Distributions of several clinico-pathologic characteristics differed between groups. Patients who were premenopausal post-chemotherapy in SOFT were younger on average. The median duration of adjuvant chemotherapy was 18 weeks in both groups. There were 231 (12%) BC events after post-landmark median follow-up of about 5 years. Concurrent use of triptorelin with chemotherapy was not associated with a significant difference in post-landmark BCFI compared with sequential triptorelin post-chemotherapy, either in the overall population (HR = 1.11, 95% CI 0.72-1.72; P = 0.72; 4-year BCFI 89% in both groups), or in the subgroup of 692 women SOFT after about 5 years median follow-up, with limited statistical power especially for the subgroup <40 years, neither

  18. The effects of sequential versus concurrent chemotherapy and radiotherapy on survival and toxicity in patients with newly diagnosed high-grade astrocytoma

    International Nuclear Information System (INIS)

    Kleinberg, Lawrence; Grossman, Stuart A.; Piantadosi, Steven; Zeltzman, Michel; Wharam, Moody

    1999-01-01

    Purpose: To determine the effects of sequential versus concurrent administration of cranial radiotherapy and cisplatin/carmustine (BCNU) chemotherapy on survival and toxicity in newly diagnosed high-grade astrocytomas. Methods and Materials: From 1988 to 1996, 101 patients were treated on 2 therapeutic protocols for malignant glioma that used the identical chemotherapy regimen but differed in the timing of cranial radiotherapy. The eligibility criteria for the 2 protocols were identical. In the first protocol (1988-1991, 52 patients), cisplatin 120 mg/BCNU 120 mg i.v. over 72 h, was given for 3 monthly cycles prior to cranial radiotherapy. After a response rate of 42%, with a median survival of 13 months was achieved with this sequential regimen, a successor protocol (1992-1996, 49 patients) was developed in which cranial radiotherapy began concurrently with the start of the identical chemotherapy regimen. Chemotherapy was delayed but not discontinued if prolonged grade III/IV hematologic toxicity was experienced, but protocol therapy was discontinued if disease progression or thromboembolic events occurred. Survival outcome and hematologic toxicity were compared for the patients treated on these protocols. Results: Seventy-seven percent of sequentially-treated patients and 68% of concurrently-treated patients completed all planned therapy. Kaplan-Meier survival was similar to concurrent or sequential administration of chemotherapy and radiotherapy (median 12.8 months vs. 13.8 months, respectively). Hematologic toxicity was significantly less in sequentially- versus concurrently-treated patients, with median nadir per cycle (2.9 vs. 1.8 x 10 3 /mm 3 ) (p < 0.001), and incidence of grade 3/4 leukopenia 40% versus 77% (p = 0.002). There was also an increase in platelet transfusion requirements in concurrently-treated patients, but no significant worsening of anemia. We postulate that the worsened leukopenia results from the effects of concurrent radiotherapy on

  19. Aprepitant, granisetron, and dexamethasone for prevention of chemotherapy-induced nausea and vomiting after high-dose melphalan in autologous transplantation for multiple myeloma: results of a randomized, placebo-controlled phase III trial.

    Science.gov (United States)

    Schmitt, Thomas; Goldschmidt, Hartmut; Neben, Kai; Freiberger, Anja; Hüsing, Johannes; Gronkowski, Martina; Thalheimer, Markus; Pelzl, Le Hang; Mikus, Gerd; Burhenne, Jürgen; Ho, Anthony D; Egerer, Gerlinde

    2014-10-20

    The optimal regimen to prevent chemotherapy-induced nausea and vomiting (CINV) for patients undergoing high-dose chemotherapy and autologous stem-cell transplantation (ASCT) is unclear. To evaluate the effect of aprepitant in addition to a standard regimen, we conducted this randomized, placebo-controlled phase III trial. Patients with multiple myeloma were randomly assigned at a one-to-one ratio to receive either aprepitant (125 mg orally on day 1 and 80 mg orally on days 2 to 4), granisetron (2 mg orally on days 1 to 4), and dexamethasone (4 mg orally on day 1 and 2 mg orally on days 2 to 3) or matching placebo, granisetron (2 mg orally on days 1 to 4), and dexamethasone (8 mg orally on day 1 and 4 mg orally on days 2 to 3). Melphalan 100 mg/m(2) was administered intravenously on days 1 to 2. ASCT was performed on day 4. The primary end point (complete response) was defined as no emesis and no rescue therapy within 120 hours of melphalan administration. Quality of life was assessed by modified Functional Living Index-Emesis (FLIE) questionnaire on days -1 and 6. Overall, 362 patients were available for the efficacy analysis (181 in each treatment arm). Significantly more patients receiving aprepitant reached the primary end point (58% v 41%; odds ratio [OR], 1.92; 95% CI, 1.23 to 3.00; P = .0042). Absence of major nausea (94% v 88%; OR, 2.37; 95% CI, 1.09 to 5.15; P = .026) and emesis (78% v 65%; OR, 1.99; 95% CI, 1.25 to 3.18; P = .0036) within 120 hours was increased by aprepitant. Mean total FLIE score (± standard deviation) was 114 ± 18 for aprepitant and 106 ± 26 for placebo (P < .001). The addition of aprepitant resulted in significantly less CINV and had a positive effect on quality of life. © 2014 by American Society of Clinical Oncology.

  20. 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.

    Science.gov (United States)

    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.

  1. Anemia During Sequential Induction Chemotherapy and Chemoradiation for Head and Neck Cancer: The Impact of Blood Transfusion on Treatment Outcome

    International Nuclear Information System (INIS)

    Bhide, Shreerang A.; Ahmed, Merina; Rengarajan, Vijayan; Powell, Ceri; Miah, Aisha; Newbold, Kate; Nutting, Christopher M.; Harrington, Kevin J.

    2009-01-01

    Purpose: Sequential treatment (chemotherapy followed by concomitant chemoradiation; CCRT) is increasingly being used for radical treatment of squamous cell cancer of the head and neck (SCCHN), which results in increased myelosuppression. In this study, we review the incidence of anemia and the effect of a policy of hemoglobin (Hb) maintenance by blood transfusion on disease outcomes in these patients. Methods and Materials: Retrospective review of the records of patients with SCCHN treated with sequential CCRT formed the basis of this study. The incidence of anemia and statistics on blood transfusion were documented. For the purpose of outcome analyses, patients were divided into four categories by (1) transfusion status, (2) nadir Hb concentration, (3) number of transfusion episodes, and (4) number of units of blood transfused (NOUT). Data on 3-year locoregional control (LRC), relapse-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were analyzed. Results: One hundred and sixty-nine patients were identified. The median follow-up was 23.6 months. The RFS (52% vs. 41%, p = 0.03), DSS (71% vs. 66%, p = 0.02), and OS (58% vs. 42% p = 0.005) were significantly better for patients who did not have a transfusion vs. those who did. The LRC, RFS, DSS, and OS were also significantly better for patients with nadir Hb level >12 vs. 4. Conclusion: Our study seems to suggest that blood transfusion during radical treatment for SCCHN might be detrimental. Further research should be undertaken into the complex interactions among tumor hypoxia, anemia, and the treatment of anemia before making treatment recommendations

  2. Anemia During Sequential Induction Chemotherapy and Chemoradiation for Head and Neck Cancer: The Impact of Blood Transfusion on Treatment Outcome

    Energy Technology Data Exchange (ETDEWEB)

    Bhide, Shreerang A; Ahmed, Merina [Institute of Cancer Research, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Head and Neck Unit, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Rengarajan, Vijayan; Powell, Ceri; Miah, Aisha; Newbold, Kate [Head and Neck Unit, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Nutting, Christopher M [Institute of Cancer Research, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Head and Neck Unit, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Harrington, Kevin J [Institute of Cancer Research, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Head and Neck Unit, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom)], E-mail: kevinh@icr.ac.uk

    2009-02-01

    Purpose: Sequential treatment (chemotherapy followed by concomitant chemoradiation; CCRT) is increasingly being used for radical treatment of squamous cell cancer of the head and neck (SCCHN), which results in increased myelosuppression. In this study, we review the incidence of anemia and the effect of a policy of hemoglobin (Hb) maintenance by blood transfusion on disease outcomes in these patients. Methods and Materials: Retrospective review of the records of patients with SCCHN treated with sequential CCRT formed the basis of this study. The incidence of anemia and statistics on blood transfusion were documented. For the purpose of outcome analyses, patients were divided into four categories by (1) transfusion status, (2) nadir Hb concentration, (3) number of transfusion episodes, and (4) number of units of blood transfused (NOUT). Data on 3-year locoregional control (LRC), relapse-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were analyzed. Results: One hundred and sixty-nine patients were identified. The median follow-up was 23.6 months. The RFS (52% vs. 41%, p = 0.03), DSS (71% vs. 66%, p = 0.02), and OS (58% vs. 42% p = 0.005) were significantly better for patients who did not have a transfusion vs. those who did. The LRC, RFS, DSS, and OS were also significantly better for patients with nadir Hb level >12 vs. <12 g/dL and NOUT 1-4 vs. >4. Conclusion: Our study seems to suggest that blood transfusion during radical treatment for SCCHN might be detrimental. Further research should be undertaken into the complex interactions among tumor hypoxia, anemia, and the treatment of anemia before making treatment recommendations.

  3. Sequential cisplatin/cyclophosphamide chemotherapy and abdominopelvic radiotherapy in the management of advanced ovarian cancer.

    Science.gov (United States)

    Green, J A; Warenius, H M; Errington, R D; Myint, S; Spearing, G; Slater, A J

    1988-11-01

    Forty-six previously untreated patients with advanced ovarian cancer were treated with combination chemotherapy comprising cisplatin 80 mg m-2 i.v. and cyclophosphamide 1 gm-2 i.v. every 28 days for 5 cycles. Eighty-five percent of patients received more than 75% of the calculated doses, and of 43 evaluable patients, a complete response was achieved in 31 (72%), a partial response in 4 (9.3%) and 8 patients had static or progressive disease. The actuarial survival of the whole group is 60% at a median follow-up of 2 years. Twenty-four patients in complete clinical or pathological remission were then treated with whole abdominal radiotherapy 2,500 cGy followed by a pelvic boost of 2,000 cGy. The pelvic boost was omitted in 3 patients, and the overall radiotherapy treatment time extended in a further 4 patients on account of myelosuppression. The actuarial survival of the 24 patients receiving both treatments at a median of 30 months follow-up is 75%. In the 10 patients with negative second-look procedures completing both treatments there have been no tumour related deaths at a median follow-up of 33 months.

  4. Breast conserving treatment of breast carcinoma T2 ({<=} 4 cm) and T3 by neoadjuvant chemotherapy, quadrantectomy, high dose rate brachytherapy as a boost, external beam radiotherapy and adjuvant chemotherapy: local control and overall survival analysis; Tratamento conservador do cancer de mama T2 ({<=} 4 cm) e T3 por quimioterapia neoadjuvante, quadrantectomia, braquiterapia com alta taxa de dose como reforco de dose, teleterapia complementar e quimioterapia adjuvante: analise de controle local e sobrevida global

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Celia Regina; Miziara Filho, Miguel Abrao; Fogaroli, Ricardo Cesar; Baraldi, Helena Espindola; Pellizzon, Antonio Cassio Assis; Pelosi, Edilson Lopes [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Radioterapia], e-mail: celiarsoares@terra.com.br; Fristachi, Carlos Elias [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Onco-Ginecologia e Mastologia; Paes, Roberto Pinto [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil)

    2008-12-15

    Objective: to assess the treatment of breast cancer T2 ({<=} 4 cm) and T3 through neoadjuvant chemotherapy, quadrantectomy and high dose rate brachytherapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering local control and overall survival. Material and method: this clinical prospective descriptive study was based on the evaluation of 88 patients ranging from 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIb and IIIa, responsive to the neoadjuvant chemotherapy, treated from June/1995 to December/2006. Median follow-up was 58 months. Using clinical methods the tumor was evaluated before and after three or four cycles of chemotherapy based on anthracyclines. Overall survival and local control were assessed according to Kaplan-Meier methodology. Results: Local control and overall survival in five years were 90% and 73.5%, respectively. Conclusion: local control and overall survival were comparable to other forms of treatment. (author)

  5. Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

    International Nuclear Information System (INIS)

    Salama, Joseph K.; Stinchcombe, Thomas E.; Gu Lin; Wang Xiaofei; Morano, Karen; Bogart, Jeffrey A.; Crawford, Jeffrey C.; Socinski, Mark A.; Blackstock, A. William; Vokes, Everett E.

    2011-01-01

    Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non–small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

  6. Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

    Energy Technology Data Exchange (ETDEWEB)

    Salama, Joseph K., E-mail: joseph.salama@duke.edu [Duke University Medical Center, Durham, NC (United States); Stinchcombe, Thomas E. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Gu Lin; Wang Xiaofei [CALGB Statistical Center, Duke University Medical Center, Durham, NC (United States); Morano, Karen [Quality Assurance Review Center, Lincoln, RI (United States); Bogart, Jeffrey A. [State University of New York Upstate Medical University, Syracuse, NY (United States); Crawford, Jeffrey C. [Duke University Medical Center, Durham, NC (United States); Socinski, Mark A. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Blackstock, A. William [Wake Forest University School of Medicine, Winston-Salem, NC (United States); Vokes, Everett E. [University of Chicago, Chicago, IL (United States)

    2011-11-15

    Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

  7. Patterns of failure following high-dose chemotherapy and stem cell rescue for relapsed/refractory non-Hodgkin's lymphoma: implications for the use of adjuvant involved field radiotherapy

    International Nuclear Information System (INIS)

    Mundt, Arno J.; Williams, Stephanie F.; Hallahan, Dennis; Weichselbaum, Ralph R.

    1996-01-01

    Purpose: Recent data have suggested a benefit to involved-field radiotherapy (IFRT) in conjunction with high-dose chemotherapy (HDCT) and autologous stem cell rescue (SCR) in patients with metastatic breast cancer, advanced neuroblastoma and relapsed/refractory Hodgkin's disease. The purpose of this study is to determine whether a similar role exists for IFRT in patients with relapsed/refractory Non-Hodgkin's Lymphoma (NHL) undergoing HDCT. Methods/Materials: Forty-nine adult patients with refractory (17) or relapsed (32) NHL underwent HDCT with SCR between 9/90 and 9/95. The most common histology was diffuse large cell (42.8%). Initial stages were I (3), II (23), III (5) and IV (18). All patients had a history of conventional chemotherapy (median regimens 2, range 1-3), 17 (34.7%) had previous RT. Treatment consisted of conventional dose induction chemotherapy followed by high-dose intensification with cytoxan, busulfan and either ara-C or VP-16. Seven patients (14.3%) received IFRT (median dose 34.5 Gy, range 20-45 Gy) to eleven sites of persistent disease following HDCT (HDCT+IFRT). Patients treated with RT to sites of progressive disease following HDCT (salvage RT) were not included in the HDCT+IFRT group. No patient received total body irradiation (TBI). One hundred sixty four sites were identified. Sites were designated as amenable or not to IFRT and divided into those achieving a complete response to induction (IndCR) and those which did not (non-IndCR). An amenable site is defined as disease localized to either an organ or nodal chain and encompassable within a standard RT portal. Relapse sites were designated as in previous (involved) sites (present prior to HDCT) or in new (uninvolved) sites. Median followup was 19.7 months (range, 1-57.3 months). Results: The 4-year actuarial progression-free (PFS), cause-specific (CSS) and overall (OS) survivals of the entire group were 36.4%, 45.9% and 34.9%, respectively. Excluding toxic deaths, 20 (47.6%) patients

  8. Randomised study of sequential versus combination chemotherapy with capecitabine, irinotecan and oxaliplatin in advanced colorectal cancer, an interim safety analysis. A Dutch Colorectal Cancer Group (DCCG) phase III study.

    NARCIS (Netherlands)

    Koopman, M.; Antonini, N.; Douma, J.; Wals, J.; Honkoop, A.H.; Erdkamp, F.L.; Jong, R.S. de; Rodenburg, C.J.; Vreugdenhil, G.R.; Akkermans-Vogelaar, J.M.; Punt, C.J.A.

    2006-01-01

    BACKGROUND: Results on overall survival in randomised studies of mono- versus combination chemotherapy in advanced colorectal cancer patients may have been biased by an imbalance in salvage treatments. This is the first randomised study that evaluates sequential versus combination chemotherapy with

  9. Randomised study of sequential versus combination chemotherapy with capecitabine, irinotecan and oxaliplatin in advanced colorectal cancer, an interim safety analysis. A Dutch Colorectal Cancer Group (DCCG) phase III study

    NARCIS (Netherlands)

    Koopman, M.; Antonini, N. F.; Douma, J.; Wals, J.; Honkoop, A. H.; Erdkamp, F. L. G.; de Jong, R. S.; Rodenburg, C. J.; Vreugdenhil, G.; Akkermans-Vogelaar, J. M.; Punt, C. J. A.

    2006-01-01

    Results on overall survival in randomised studies of mono- versus combination chemotherapy in advanced colorectal cancer patients may have been biased by an imbalance in salvage treatments. This is the first randomised study that evaluates sequential versus combination chemotherapy with a

  10. Treatment response evaluation with 18F-FDG PET/CT and 18F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation.

    Science.gov (United States)

    Sachpekidis, Christos; Hillengass, J; Goldschmidt, H; Wagner, B; Haberkorn, U; Kopka, K; Dimitrakopoulou-Strauss, A

    2017-01-01

    The aim of this study was to assess the combined use of the radiotracers 18 F-FDG and 18 F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with 18 F-FDG and 18 F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, 18 F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, 18 F-FDG PET/CT-based treatment response revealed CR in 14 patients ( 18 F-FDG PET/CT CR), PR in 11 patients ( 18 F-FDG PET/CT PR) and progressive disease in four patients ( 18 F-FDG PET/CT PD). In terms of 18 F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, 18 F-NaF PET/CT depicted 56 of the 129 18 F-FDG positive lesions (43 %). Follow-up 18 F-NaF PET/CT showed persistence of 81.5 % of the baseline 18 F-NaF positive MM lesions after treatment, despite the fact that 64

  11. Non-Cross Resistant Sequential Single Agent Chemotherapy in First-Line Advanced Non-Small Cell Lung Cancer Patients: Results of a Phase II Study

    Directory of Open Access Journals (Sweden)

    V. Surmont

    2009-01-01

    Full Text Available Background. sequential chemotherapy can maintain dose intensity and preclude cumulative toxicity by increasing drug diversity. Purpose. to investigate the toxicity and efficacy of the sequential regimen of gemcitabine followed by paclitaxel in first line advanced stage non-small cell lung cancer (NSCLC patients with good performance status (PS. Patients and methods. gemcitabine 1250 mg/m2 was administered on day 1 and 8 of course 1 and 2; Paclitaxel 150 mg/m2 on day 1 and 8 of course 3 and 4. Primary endpoint was response rate (RR, secondary endpoints toxicity and time to progression (TTP. Results. Of the 21 patients (median age 56, range 38–80 years; 62% males, 38% females 10% (2/21 had stage IIIB, 90% (19/21 stage IV, 15% PS 0, 85% PS 1. 20% of patients had a partial response, 30% stable disease, 50% progressive disease. Median TTP was 12 weeks (range 6–52 weeks, median overall survival (OS 8 months (range 1–27 months, 1-year survival was 33%. One patient had grade 3 hematological toxicity, 2 patients a grade 3 peripheral neuropathy. Conclusions. sequential administration of gemcitabine followed by paclitaxel in first line treatment of advanced NSCLC had a favourable toxicity profile, a median TTP and OS comparable with other sequential trials and might , therefore, be a treatment option for NSCLC patients with high ERCC1 expression.

  12. Long-term follow-up in patients treated with larynx preservation approach using sequential chemotherapy and radiation therapy: the Memorial Hospital experience

    Energy Technology Data Exchange (ETDEWEB)

    Maluf, Fernando; Sherman, Eric J.; Bosl, George J.; Pfister, David G. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Dept. of Medicine. Div. of Solid Tumor Oncology; Kraus, Dennis H.; Shaha, Ashok; Shah, Jatin P. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States).Dept. of Surgery. Head and Neck Service; Zelefsky, Michael J. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Dept. of Radiation Oncology]. E-mail: pfisterd@mskcc.org

    2000-06-01

    While many combined modality, organ preservation programs are reported in the literature, few provide long-term follow-up with functional outcomes. The goal of this report is to provide this outcome data for patients treated with a sequential chemotherapy/radiotherapy (CT/RT) approach - the only strategy successfully compared to surgery and RT in randomized trials to date - treated at our institution with a median follow-up of over 10 years. Eligible patients had advanced, resectable, histologically-confirmed squamous cell carcinomas of larynx or pharynx for which standard surgical management would have jeopardized the larynx. Treatment occurred as part of three consecutive larynx preservation protocols and consisted of three cycles of induction, cisplatin-based chemotherapy followed, if the primary site had a major response, by definitive dose radiation therapy (65-70 Gy to sites of initial disease bulk) via conventional fractionation (1.8-2 Gy fraction). If the tumor did not respond to the induction chemotherapy or persisted after radiation therapy, appropriate locoregional treatment was pursued. Response to induction chemotherapy, initial rendered disease-free rate, local control with a functional larynx (without any surgery except biopsy to the primary site, permanent tracheostomy or gastrostomy - LCLP), and actuarial survival rates were calculated. A multivariate assessment of prognostic variables was performed using Cox-proportional hazards model to evaluate for predictors of successful larynx preservation. One hundred and ten patients (109 evaluable) with cancer of the larynx (40%), hypopharynx (29%), and oropharynx (30%) were enrolled from 1983 to 1990. The median age was 60 years With a median Karnofsky Performance Status of 80%. The stage of the patients consisted of 33% T4, 74% node positive, and 69% stage IV. The major response rate at the primary site to induction chemotherapy was 74% (complete response in 36%). Seventy-eight percent were rendered

  13. Long-term follow-up in patients treated with larynx preservation approach using sequential chemotherapy and radiation therapy: the Memorial Hospital experience

    International Nuclear Information System (INIS)

    Maluf, Fernando; Sherman, Eric J.; Bosl, George J.; Pfister, David G.; Kraus, Dennis H.; Shaha, Ashok; Shah, Jatin P.; Zelefsky, Michael J.

    2000-01-01

    While many combined modality, organ preservation programs are reported in the literature, few provide long-term follow-up with functional outcomes. The goal of this report is to provide this outcome data for patients treated with a sequential chemotherapy/radiotherapy (CT/RT) approach - the only strategy successfully compared to surgery and RT in randomized trials to date - treated at our institution with a median follow-up of over 10 years. Eligible patients had advanced, resectable, histologically-confirmed squamous cell carcinomas of larynx or pharynx for which standard surgical management would have jeopardized the larynx. Treatment occurred as part of three consecutive larynx preservation protocols and consisted of three cycles of induction, cisplatin-based chemotherapy followed, if the primary site had a major response, by definitive dose radiation therapy (65-70 Gy to sites of initial disease bulk) via conventional fractionation (1.8-2 Gy fraction). If the tumor did not respond to the induction chemotherapy or persisted after radiation therapy, appropriate locoregional treatment was pursued. Response to induction chemotherapy, initial rendered disease-free rate, local control with a functional larynx (without any surgery except biopsy to the primary site, permanent tracheostomy or gastrostomy - LCLP), and actuarial survival rates were calculated. A multivariate assessment of prognostic variables was performed using Cox-proportional hazards model to evaluate for predictors of successful larynx preservation. One hundred and ten patients (109 evaluable) with cancer of the larynx (40%), hypopharynx (29%), and oropharynx (30%) were enrolled from 1983 to 1990. The median age was 60 years With a median Karnofsky Performance Status of 80%. The stage of the patients consisted of 33% T4, 74% node positive, and 69% stage IV. The major response rate at the primary site to induction chemotherapy was 74% (complete response in 36%). Seventy-eight percent were rendered

  14. Gamma dosimetry of high doses

    International Nuclear Information System (INIS)

    Martinez C, T.; Galvan G, A.; Canizal, G.

    1991-01-01

    The gamma dosimetry of high doses is problematic in almost all the classic dosemeters either based on the thermoluminescence, electric, chemical properties, etc., because they are saturated to very high dose and they are no longer useful. This work carries out an investigation in the interval of high doses. The solid system of heptahydrate ferrous sulfate, can be used as solid dosemeter of routine for high doses of radiation. The proposed method is simple, cheap and it doesn't require sophisticated spectrophotometers or spectrometers but expensive and not common in some laboratories

  15. Treatment response evaluation with {sup 18}F-FDG PET/CT and {sup 18}F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Sachpekidis, Christos [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Bern, Department of Nuclear Medicine, Inselspital, Bern University Hospital, Bern (Switzerland); Hillengass, J.; Wagner, B. [University Hospital Heidelberg, Department of Internal Medicine V, Heidelberg (Germany); Goldschmidt, H. [University Hospital Heidelberg, Department of Internal Medicine V, Heidelberg (Germany); National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg (Germany); Haberkorn, U. [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Kopka, K. [German Cancer Research Center (DKFZ), Department of Radiopharmaceutical Chemistry, Heidelberg (Germany); Dimitrakopoulou-Strauss, A. [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany)

    2017-01-15

    The aim of this study was to assess the combined use of the radiotracers {sup 18}F-FDG and {sup 18}F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with {sup 18}F-FDG and {sup 18}F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, {sup 18}F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, {sup 18}F-FDG PET/CT-based treatment response revealed CR in 14 patients ({sup 18}F-FDG PET/CT CR), PR in 11 patients ({sup 18}F-FDG PET/CT PR) and progressive disease in four patients ({sup 18}F-FDG PET/CT PD). In terms of {sup 18}F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, {sup 18}F-NaF PET/CT depicted 56 of the 129 {sup 18}F-FDG positive lesions (43 %). Follow-up {sup 18}F-NaF PET/CT showed persistence of 81.5 % of the baseline {sup 18}F

  16. Induction chemotherapy with carboplatin, irinotecan, and paclitaxel followed by high dose three-dimension conformal thoracic radiotherapy (74 Gy) with concurrent carboplatin, paclitaxel, and gefitinib in unresectable stage IIIA and stage IIIB non-small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Morris, David E; Lee, Carrie B; Moore, Dominic T; Hayes, D Neil; Halle, Jan S; Rivera, M Patricia; Rosenman, Julian G; Socinski, Mark A

    2008-03-01

    Combined modality therapy is a standard therapy for patients with unresectable stage III non-small cell lung cancer (NSCLC). Gefitinib is active in advanced NSCLC, and in preclinical models, it potentiates the activity of radiation therapy. We investigate the tolerability of gefitinib in combined modality therapy in combination with three-dimensional thoracic conformal radiation therapy (3-dimensional TCRT). Stage III patients with a good performance status were treated with induction chemotherapy (carboplatin area under the curve [AUC] of 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) with pegfilgrastim support followed by concurrent chemotherapy (carboplatin AUC 2, and paclitaxel 45 mg/m(2) weekly) and gefitinib 250 mg daily beginning on day 43 with 3-dimensional TCRT to 74 Gy. Between March 2004 and January 2006, 23 patients received treatment on the trial: median age 62 years (range 44-82), 52% female, 61% stage IIIA, 61% performance status 0, 17% > or =5% weight loss, and 91% underwent positron emission tomography staging. Induction chemotherapy with pegfilgrastim support was well tolerated and active (partial response rate, 24%; stable disease, 76%; and early progression, 0%). Twenty-one patients initiated the concurrent chemoradiation, and 20 patients completed therapy to 74 Gy. The primary toxicities of concurrent chemoradiation were grade 3 esophagitis (19.5%) and cardiac arrhythmia (atrial fibrillation) (9.5%). The median progression-free survival and overall survival were 9 months (95% confidence intervals [CI]: 7-13 months) and 16 months (95% CI: 10-20 months), respectively. Treatment with induction chemotherapy and gefitinib concurrent with 3-dimensional TCRT has an acceptable toxicity and tolerability, but the survival results were disappointing.

  17. Brachytherapy treatment with high dose rate

    International Nuclear Information System (INIS)

    Santana Rodriguez, Sergio Marcelino; Rodriguez Rodriguez, Lissi Lisbet; Ciscal Chiclana, Onelio Alberto

    2009-01-01

    Retrospectively analyze results and prognostic factors of cervical cancer patients treated with radio concomitant cisplatin-based chemotherapy, radiation therapy combined modality. Methods: From January 2003 to December 2007, 198 patients with invasive cervical cancer were treated at the Oncology Department of Hospital Robau Celestino Hernandez (brachytherapy performed at INOR). The most common age group was 31 to 40 years. The histology in squamous cell carcinoma accounted for 84.3% of cases. The treatment consisted of external pelvic irradiation and vaginal brachytherapy, high dose rate. Concomitant chemotherapy consisted of cisplatin 40 mg/m2 weekly with a maximum of 70 mg for 5 weeks. Results: 66.2% of patients completed 5 cycles of chemotherapy. The median overall survival was 39 months, overall survival, disease-free survival and survival free of locoregional recurrence at 5 years of 78%, 76% and 78.6% respectively .. We found that clinical stage, histological type (adenocarcinoma worst outcome) were statistically related to level of response. Conclusions: Treatment with external pelvic radiation, brachytherapy and concurrent weekly cisplatin in patients with stage IIIB cervical cancer is feasible in the Chilean public health system, well tolerated and results comparable to international literature. (Author)

  18. Sequential treatment of tyrosine kinase inhibitors and chemotherapy for EGFR-mutated non-small cell lung cancer: a meta-analysis of Phase III trials

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2013-11-01

    Full Text Available Yiliang Zhang,1,* Yihua Sun,1,* Lei Wang,1 Ting Ye,1 Yunjian Pan,1 Haichuan Hu,1 Yongfu Yu,2 Naiqing Zhao,2 Yanyan Song,3 David Garfield,4 Haiquan Chen1 1Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, 2Department of Biostatistics, School of Public Health, Fudan University, 3Department of Pharmacology and Biostatistics, Institute of Medical Science, Shanghai Jiaotong University School of Medicine, 4ProMed Cancer Centers, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: This aim of this study was to compare the efficacy of first-line tyrosine kinase inhibitor therapy followed, upon progression, by chemotherapy with the reverse sequence in patients with EGFR-mutated non-small cell lung cancer (NSCLC in terms of overall survival. Methods: We performed a meta-analysis of studies that met the following criteria: Phase III clinical trial comparing the sequencing of epidermal growth factor receptor (EGFR tyrosine kinase inhibitors with chemotherapy in the treatment of advanced EGFR-mutated NSCLC; activating mutations reported; and availability of hazard ratio estimates with 95% confidence intervals (CIs for overall survival. Results: Six clinical trials were included in this study. The pooled hazard ratio for overall survival of the EGFR-mutated population that completed sequential treatment was 1.03 (95% CI 0.86–1.22, P=0.776. There was no statistically significant heterogeneity between the studies (tau2 =0; I2=0, 95% CI 0–0.37, P=0.548. Evidence of marked publication bias for the two treatment sequences was insufficient (P=0.145. Conclusion: In patients with advanced NSCLC and activating EGFR mutations, first-line chemotherapy followed upon progression by a tyrosine kinase inhibitor was not inferior in terms of overall survival compared with the inverse sequence. This may serve as an indication that

  19. Avascular necrosis of femoral and/or humeral heads in multiple myeloma: results of a prospective study of patients treated with dexamethasone-based regimens and high-dose chemotherapy.

    Science.gov (United States)

    Talamo, Giampaolo; Angtuaco, Edgardo; Walker, Ronald C; Dong, Li; Miceli, Marisa H; Zangari, Maurizio; Tricot, Guido; Barlogie, Bart; Anaissie, Elias

    2005-08-01

    To assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy. A total of 553 consecutive assessable patients were enrolled onto a treatment protocol consisting of dexamethasone-containing induction chemotherapy, autologous stem-cell transplantation, consolidation chemotherapy, and maintenance with interferon alfa. Patients were randomly assigned to receive thalidomide (269 patients) or no thalidomide (284 patients) throughout the study period. With a median follow-up of 33 months (range, 5 to 114 months), AVN of the femoral head(s) developed in 49 patients (9%). Median time to onset of AVN was 12 months (range, 2 to 41 months). Three risk factors for AVN were identified by multivariate analysis: cumulative dexamethasone dose (odds ratio [OR], 1.028; 95% CI, 1.012 to 1.044; P = .0006 [per 40 mg dexamethasone]), male sex (OR, 0.390; 95% CI, 0.192 to 0.790; P = .009), and younger age (OR, 0.961; 95% CI, 0.934 to 0.991 per year; P = .0122). Thalidomide-treated patients had a prevalence of AVN similar to that of the control group (8% v 10%, respectively; P = .58). AVN-related pain and limited range of motion of the affected joint were present in only nine and four patients, respectively, and four patients underwent hip replacement because of AVN. Fluorine-18 fluorodeoxyglucose positron emission tomography failed to detect abnormal uptake in the AVN-affected bones. AVN is a rare and usually asymptomatic complication during myeloma therapy. Cumulative dexamethasone dose, male sex, and younger age, but not thalidomide, increase the risk of AVN.

  20. Evaluation of the risk factors associated with high-dose chemotherapy-induced dysgeusia in patients undergoing autologous hematopoietic stem cell transplantation: possible usefulness of cryotherapy in dysgeusia prevention.

    Science.gov (United States)

    Okada, Naoto; Hanafusa, Takeshi; Abe, Shinji; Sato, Chiemi; Nakamura, Toshimi; Teraoka, Kazuhiko; Abe, Masahiro; Kawazoe, Kazuyoshi; Ishizawa, Keisuke

    2016-09-01

    Dysgeusia is one of the sporadic adverse effects induced by chemotherapy, but it remains poorly understood. The aim of this study was to retrospectively identify the risk factors related with dysgeusia in patients undergoing autologous hematopoietic stem cell transplantation (AHSCT). Forty-eight patients with myeloma or lymphoma undergoing AHSCT were enrolled in this study. Data regarding dysgeusia and symptoms were collected by interviews conducted by medical workers. Patient characteristics and unfavorable effects induced by dysgeusia were obtained from medical records and analyzed. Logistic regression analysis was performed to identify the risk factors related with dysgeusia. Of the 48 patients, 20 (42 %) had dysgeusia after AHSCT. The total period of parenteral nutrition (TPN) administration and period of decreased oral intake in the dysgeusia group were statistically longer than those in the non-dysgeusia group. Multivariate analyses revealed that oral mucositis (odds ratio: 30.3; p cryotherapy was the independent suppressive factor of dysgeusia (odds ratio: 0.14; p cryotherapy was an independent suppressive factor for dysgeusia. Therefore, oral cryotherapy should be implemented into the regimen of supportive care management in patients undergoing AHSCT.

  1. In vitro synergistic antitumor efficacy of sequentially combined chemotherapy/icotinib in non‑small cell lung cancer cell lines.

    Science.gov (United States)

    Wang, Min-Cong; Liang, Xuan; Liu, Zhi-Yan; Cui, Jie; Liu, Ying; Jing, Li; Jiang, Li-Li; Ma, Jie-Qun; Han, Li-Li; Guo, Qian-Qian; Yang, Cheng-Cheng; Wang, Jing; Wu, Tao; Nan, Ke-Jun; Yao, Yu

    2015-01-01

    The concurrent administration of chemotherapy and epidermal growth factor receptor‑tyrosine kinase inhibitors (EGFR‑TKIs) has previously produced a negative interaction and failed to confer a survival benefit to non‑small cell lung cancer (NSCLC) patients compared with first‑line cytotoxic chemotherapy. The present study aimed to investigate the optimal schedule of the combined treatment of cisplatin/paclitaxel and icotinib in NSCLC cell lines and clarify the underlying mechanisms. HCC827, H1975, H1299 and A549 human NSCLC cell lines with wild‑type and mutant EGFR genes were used as in vitro models to define the differential effects of various schedules of cisplatin/paclitaxel with icotinib treatments on cell growth, proliferation, cell cycle distribution, apoptosis, and EGFR signaling pathway. Sequence‑dependent antiproliferative effects differed among the four NSCLC cell lines, and were not associated with EGFR mutation, constitutive expression levels of EGFR or downstream signaling molecules. The antiproliferative effect of cisplatin plus paclitaxel followed by icotinib was superior to that of cisplatin or paclitaxel followed by icotinib in the HCC827, H1975, H1299 and A549 cell lines, and induced more cell apoptosis and G0/G1 phase arrest. Cisplatin and paclitaxel significantly increased the expression of EGFR phosphorylation in the HCC827 cell line. However, only paclitaxel increased the expression of EGFR phosphorylation in the H1975 cell line. Cisplatin/paclitaxel followed by icotinib influenced the expression of p‑EGFR and p‑AKT, although the expression of p‑ERK1/2 remained unchanged. The results suggest that the optimal schedule of the combined treatment of cisplatin/paclitaxel and icotinib differed among the NSCLC cell lines. The results also provide molecular evidence to support clinical treatment strategies for NSCLC patients.

  2. Phase I Study of Concurrent High-Dose Three-Dimensional Conformal Radiotherapy With Chemotherapy Using Cisplatin and Vinorelbine for Unresectable Stage III Non-Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sekine, Ikuo, E-mail: isekine@ncc.go.jp [Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan); Sumi, Minako; Ito, Yoshinori [Division of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Horinouchi, Hidehito; Nokihara, Hiroshi; Yamamoto, Noboru; Kunitoh, Hideo; Ohe, Yuichiro; Kubota, Kaoru; Tamura, Tomohide [Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan)

    2012-02-01

    Purpose: To determine the maximum tolerated dose in concurrent three-dimensional conformal radiotherapy (3D-CRT) with chemotherapy for unresectable Stage III non-small-cell lung cancer (NSCLC). Patients and Methods: Eligible patients with unresectable Stage III NSCLC, age {>=}20 years, performance status 0-1, percent of volume of normal lung receiving 20 GY or more (V{sub 20}) {<=}30% received three to four cycles of cisplatin (80 mg/m{sup 2} Day 1) and vinorelbine (20 mg/m{sup 2} Days 1 and 8) repeated every 4 weeks. The doses of 3D-CRT were 66 Gy, 72 Gy, and 78 Gy at dose levels 1 to 3, respectively. Results: Of the 17, 16, and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled at dose levels 1 to 3, respectively. The main reasons for exclusion were V{sub 20} >30% (n = 10) and overdose to the esophagus (n = 8) and brachial plexus (n = 2). There were 26 men and 5 women, with a median age of 60 years (range, 41-75). The full planned dose of radiotherapy could be administered to all the patients. Grade 3-4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, Grade 3 esophagitis, and Grade 3 pulmonary toxicity were noted in 1 patient, 2 patients, and 1 patient, respectively. The dose-limiting toxicity was noted in 17% of the patients at each dose level. The median survival and 3-year and 4-year survival rates were 41.9 months, 72.3%, and 49.2%, respectively. Conclusions: 72 Gy was the maximum dose that could be achieved in most patients, given the predetermined normal tissue constraints.

  3. Selections of appropriate regimen of high-dose chemotherapy combined with adoptive cellular therapy with dendritic and cytokine-induced killer cells improved progression-free and overall survival in patients with metastatic breast cancer: reargument of such contentious therapeutic preferences.

    Science.gov (United States)

    Ren, Jun; Di, Lijun; Song, Guohong; Yu, Jing; Jia, Jun; Zhu, Yuling; Yan, Ying; Jiang, Hanfang; Liang, Xu; Che, Li; Zhang, Jie; Wan, Fengling; Wang, Xiaoli; Zhou, Xinna; Lyerly, Herbert Kim

    2013-10-01

    We hypothesized that combination of dendritic cell (DC) with autologous cytokine-induced killer (CIK) immunotherapy in setting of high-dose chemotherapy (HDC) would be effective for selected metastatic breast cancer (MBC) patients. Our previous work showed thiotepa could eradicate breast cancer stem cells. From 2004 to 2009, 79 patients received standard dose chemotherapy (SDC) of 75 mg/m(2) docetaxel and 75 mg/m(2) thiotepa versus 87 patients of HDC + DC/CIK: 120 mg/m(2) docetaxel to mobilize peripheral CD34(+) progenitor cells, a sequence of HDC (120 mg/m(2) docetaxel, plus 175 mg/m(2) thiotepa) + DC/CIK, with or without 400 mg/m(2) carboplatin depending upon bone marrow function. The endpoints were response rates (RR), progression-free survival (PFS), and overall survival (OS). Compared with SDC, PFS and OS were improved in HDC + DC/CIK (median PFS 10.2 vs. 3.7 months, P < 0.001; median OS 33.1 vs. 15.2 months, P < 0.001). Patients of pre-menopausal, HDC as first-line treatment after metastasis, or with visceral metastasis showed prolonged PFS and OS. SDC group also achieved the similar response as previous reports. Our study demonstrated the novel combination of HDC with DC/CIK to be an effective choice for the selected MBC population, in which choosing appropriate chemo regimens played important roles, and also specific HDC regimen plus DC/CIK immunotherapy showed the clinical benefits compared with chemotherapy alone.

  4. Breast conserving treatment of locally advanced carcinoma T2 and T3 after neoadjuvant chemotherapy followed by quadrantectomy and high dose-rate brachytherapy, as a boost, complementary teletherapy and adjuvant chemotherapy; Tratamento conservador dos carcinomas de mama localmente avancados T2 e T3, apos quimioterapia neoadjuvante, com quadrantectomia e braquiterapia de alta taxa de dose como reforco de dose, teleterapia complementar e quimioterapia adjuvante

    Energy Technology Data Exchange (ETDEWEB)

    Fristachi, Carlos Elias [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Onco-Ginecologia e Mastologia]. E-mail: cefristachi@uol.com.br; Miziara Filho, Miguel Abrao; Soares, Celia Regina; Fogaroli, Ricardo Cesar; Pelosi, Edilson Lopes; Martins, Homero Lavieri Martins [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Radioterapia; Baracat, Fausto Farah [Hospital do Servidor Publico Estadual de Sao Paulo (HSPE), SP (Brazil). Servico de Ginecologia e Mastologia; Piato, Sebastiao [Irmandade da Santa Casa de Misericordia de Sao Paulo, SP (Brazil). Dept. de Obstetricia e Ginecologia (DOGI)

    2005-07-01

    Objective: to assess the treatment of breast cancer T2 and T3(T > = 4 cm), through neoadjuvant chemotherapy, quadrantectomy and high-dose-rate (HDR) brachytherapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering its method problems, its esthetics results, the aspect of local control, overall survival, and disease-free survival. Patients and method: this clinical prospective descriptive study was based on the evaluation of 26 patients ranging from 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIB and IIIA, responsive to the neoadjuvant chemotherapy. Early and late radiotherapy complications were evaluated according to the criteria established by the RTOG/EORTC (Radiotherapy and Oncology Group /European Organization for Research and Treatment of Cancer) groups. Esthetics evaluation was done in accordance with the criteria set by a plastic surgeon. Local control was evaluated by clinical method, mammography and ultrasonography. Overall survival (OS) and the disease-free survival (DFS) were assessed according to Kaplan-Meier methodology. All the patients were treated at the Dr. Arnaldo Vieira de Carvalho Cancer Institute, from June/1995 to November/2001, and evaluated in March, 2002, with median follow-up of 28.7 months. Results: early complications were observed in 8 patients (30.6%). Two patients were classified as G3 and G4 (RTOG/EORTC). Six patients had late complications and three of them (11.5%) were classified as G3 and G4. One patient (3.8%) had local recurrence, 64 months after having local treatment. Esthetics results were considered good or regular in 16 patients (60.5%) out of 24 patients who were examined. Overall survival and disease-free survival in 24, 36 and 60 months were 100%, 92.3% and 83.1% respectively. Conclusion: early and late radiotherapy complications were considerate high when compared to literature, but esthetic results were considered acceptable. RL, OS and DFS were comparable to other

  5. Sequential versus simultaneous use of chemotherapy and gonadotropin-releasing hormone agonist (GnRHa) among estrogen receptor (ER)-positive premenopausal breast cancer patients: effects on ovarian function, disease-free survival, and overall survival.

    Science.gov (United States)

    Zhang, Ying; Ji, Yajie; Li, Jianwei; Lei, Li; Wu, Siyu; Zuo, Wenjia; Jia, Xiaoqing; Wang, Yujie; Mo, Miao; Zhang, Na; Shen, Zhenzhou; Wu, Jiong; Shao, Zhimin; Liu, Guangyu

    2018-04-01

    To investigate ovarian function and therapeutic efficacy among estrogen receptor (ER)-positive, premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonist (GnRHa) and chemotherapy simultaneously or sequentially. This study was a phase 3, open-label, parallel, randomized controlled trial (NCT01712893). Two hundred sixteen premenopausal patients (under 45 years) diagnosed with invasive ER-positive breast cancer were enrolled from July 2009 to May 2013 and randomized at a 1:1 ratio to receive (neo)adjuvant chemotherapy combined with sequential or simultaneous GnRHa treatment. All patients were advised to receive GnRHa for at least 2 years. The primary outcome was the incidence of early menopause, defined as amenorrhea lasting longer than 12 months after the last chemotherapy or GnRHa dose, with postmenopausal or unknown follicle-stimulating hormone and estradiol levels. The menstrual resumption period and survivals were the secondary endpoints. The median follow-up time was 56.9 months (IQR 49.5-72.4 months). One hundred and eight patients were enrolled in each group. Among them, 92 and 78 patients had complete primary endpoint data in the sequential and simultaneous groups, respectively. The rates of early menopause were 22.8% (21/92) in the sequential group and 23.1% (18/78) in the simultaneous group [simultaneous vs. sequential: OR 1.01 (95% CI 0.50-2.08); p = 0.969; age-adjusted OR 1.13; (95% CI 0.54-2.37); p = 0.737]. The median menstruation resumption period was 12.0 (95% CI 9.3-14.7) months and 10.3 (95% CI 8.2-12.4) months for the sequential and simultaneous groups, respectively [HR 0.83 (95% CI 0.59-1.16); p = 0.274; age-adjusted HR 0.90 (95%CI 0.64-1.27); p = 0.567]. No significant differences were evident for disease-free survival (p = 0.290) or overall survival (p = 0.514) between the two groups. For ER-positive premenopausal patients, the sequential use of GnRHa and chemotherapy showed ovarian preservation

  6. A phase II clinical trial evaluating the use of two sequential, four-drug combination chemotherapy regimens in ambulatory bronchogenic adenocarcinoma patients.

    Science.gov (United States)

    Broder, L E; Sridhar, K S; Selawry, O S; Charyulu, K N; Rao, R K; Saldana, M J; Lenz, C

    1992-12-01

    Forty-three ambulatory patients with locally advanced or metastatic bronchogenic adenocarcinoma were sequentially treated with two potentially mutually non-cross-resistant chemotherapy regimens. A new regimen, MVPF (mitomycin-c, vinblastine, procarbazine, and 5-fluorouracil), was given until progressive disease occurred. Then, a second regimen--MOCC (methotrexate, vincristine [Oncovin], cyclophosphamide, and CCNU)--was initiated. At further progression, regional disease patients received radiotherapy, whereas extensive disease patients received Phase II agents. Of the 43 patients entered on the study, 40 were evaluable. Three patients withdrew early due to poor tolerance of the regimen. The response rate for MVPF was 33% (12 of 40 PR, 1 of 40 CR) compared to a 4% (1 of 23 PR) response for MOCC (difference: p < or = .03), for a total response rate of 35%. Although there was an initial improvement in survival for responders (31.7 weeks) versus nonresponders (15.7 weeks) at the 75th percentile (p < or = .05), there was no significant difference in median survival. The hematologic toxicity was equivalent for both groups, whereas nonhematologic toxicity revealed a high incidence of nausea and vomiting in the MVPF group. It is concluded that this approach lent itself well to ambulatory care, and MVPF could be considered an alternative to cyclophosphamide-based regimens. However, the absence of a meaningful CR rate and lack of influence of response on median survival were factors limiting its effectiveness.

  7. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

    2014-11-04

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

  8. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    International Nuclear Information System (INIS)

    Selle, F.; Gligorov, J.; Richard, S.; Khalil, A.; Alexandre, I.; Avenin, D.; Provent, S.; Soares, D.G.; Lotz, J.P.

    2014-01-01

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis

  9. Sequential 18F-FDG PET/CT for early prediction of complete pathological response in breast and axilla during neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Koolen, Bas B.; Pengel, Kenneth E.; Wesseling, Jelle; Vogel, Wouter V.; Valdes Olmos, Renato A.; Vrancken Peeters, Marie-Jeanne T.F.D.; Rutgers, Emiel J.T.; Vincent, Andrew D.; Gilhuijs, Kenneth G.A.; Rodenhuis, Sjoerd

    2014-01-01

    To investigate the value of response monitoring in both the primary tumour and axillary nodes on sequential PET/CT scans during neoadjuvant chemotherapy (NAC) for predicting complete pathological response (pCR), taking the breast cancer subtype into account. In 107 consecutive patients 290 PET/CT scans were performed at baseline (PET/CT1, 107 patients), after 2 - 3 weeks of chemotherapy (PET/CT2, 85 patients), and after 6 - 8 weeks (PET/CT3, 98 patients). The relative changes in SUVmax (from baseline) of the tumour and the lymph nodes and in both combined (after logistic regression), and the changes in the highest SUVmax between scans (either tumour or lymph node) were determined and their associations with pCR of the tumour and lymph nodes after completion of NAC were assessed using receiver operating characteristic (ROC) analysis. A pCR was seen in 17 HER2-positive tumours (65 %), 1 ER-positive/HER2-negative tumour (2 %), and 16 triple-negative tumours (52 %). The areas under the ROC curves (ROC-AUC) for the prediction of pCR in HER2-positive tumours after 3 weeks were 0.61 for the relative change in tumours, 0.67 for the combined change in tumour and nodes, and 0.72 for the changes in the highest SUVmax between scans. After 8 weeks equivalent values were 0.59, 0.42 and 0.64, respectively. In triple-negative tumours the ROC-AUCs were 0.76, 0.84 and 0.76 after 2 weeks, and 0.87, 0.93 and 0.88 after 6 weeks, respectively. In triple-negative tumours a PET/CT scan after 6 weeks (three cycles) appears to be optimally predictive of pCR. In HER2-positive tumours neither a PET/CT scan after 3 weeks nor after 8 weeks seems to be useful. The changes in SUVmax of both the tumour and axillary nodes combined correlates best with pCR. (orig.)

  10. Sequential {sup 18}F-FDG PET/CT for early prediction of complete pathological response in breast and axilla during neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Koolen, Bas B. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Pengel, Kenneth E. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); Wesseling, Jelle [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Pathology, Amsterdam (Netherlands); Vogel, Wouter V.; Valdes Olmos, Renato A. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Vrancken Peeters, Marie-Jeanne T.F.D.; Rutgers, Emiel J.T. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Vincent, Andrew D. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Biometrics, Amsterdam (Netherlands); Gilhuijs, Kenneth G.A. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Rodenhuis, Sjoerd [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Medical Oncology, Amsterdam (Netherlands)

    2014-01-15

    To investigate the value of response monitoring in both the primary tumour and axillary nodes on sequential PET/CT scans during neoadjuvant chemotherapy (NAC) for predicting complete pathological response (pCR), taking the breast cancer subtype into account. In 107 consecutive patients 290 PET/CT scans were performed at baseline (PET/CT1, 107 patients), after 2 - 3 weeks of chemotherapy (PET/CT2, 85 patients), and after 6 - 8 weeks (PET/CT3, 98 patients). The relative changes in SUVmax (from baseline) of the tumour and the lymph nodes and in both combined (after logistic regression), and the changes in the highest SUVmax between scans (either tumour or lymph node) were determined and their associations with pCR of the tumour and lymph nodes after completion of NAC were assessed using receiver operating characteristic (ROC) analysis. A pCR was seen in 17 HER2-positive tumours (65 %), 1 ER-positive/HER2-negative tumour (2 %), and 16 triple-negative tumours (52 %). The areas under the ROC curves (ROC-AUC) for the prediction of pCR in HER2-positive tumours after 3 weeks were 0.61 for the relative change in tumours, 0.67 for the combined change in tumour and nodes, and 0.72 for the changes in the highest SUVmax between scans. After 8 weeks equivalent values were 0.59, 0.42 and 0.64, respectively. In triple-negative tumours the ROC-AUCs were 0.76, 0.84 and 0.76 after 2 weeks, and 0.87, 0.93 and 0.88 after 6 weeks, respectively. In triple-negative tumours a PET/CT scan after 6 weeks (three cycles) appears to be optimally predictive of pCR. In HER2-positive tumours neither a PET/CT scan after 3 weeks nor after 8 weeks seems to be useful. The changes in SUVmax of both the tumour and axillary nodes combined correlates best with pCR. (orig.)

  11. HER2 and TOP2A in high-risk early breast cancer patients treated with adjuvant epirubicin-based dose-dense sequential chemotherapy

    Directory of Open Access Journals (Sweden)

    Fountzilas George

    2012-01-01

    Full Text Available Abstract Background HER2 and TOP2A parameters (gene status, mRNA and protein expression have individually been associated with the outcome of patients treated with anthracyclines. The aim of this study was to comprehensively evaluate the prognostic/predictive significance of the above parameters in early, high-risk breast cancer patients treated with epirubicin-based, dose-dense sequential adjuvant chemotherapy. Methods In a series of 352 breast carcinoma tissues from patients that had been post-operatively treated with epirubicin-CMF with or without paclitaxel, we assessed HER2 and TOP2A gene status (chromogenic in situ hybridization, mRNA expression (quantitative reverse transcription PCR, as well as HER2 and TopoIIa protein expression (immunohistochemistry. Results HER2 and TOP2A amplification did not share the same effects on their downstream molecules, with consistent patterns observed in HER2 mRNA and protein expression according to HER2 amplification (all parameters strongly inter-related, p values Conclusions This study confirms the favorable prognostic value of HER2/TOP2A co-amplification and the adverse prognostic value of high TOP2A mRNA expression extending it to the adjuvant treatment setting in early high-risk breast cancer. The strong adverse prognostic impact of high HER2/TOP2A mRNA co-expression needs further validation in studies designed to evaluate markers predictive for anthracyclines. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12611000506998.

  12. High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group

    NARCIS (Netherlands)

    Pritchard, Jon; Cotterill, Simon J.; Germond, Shirley M.; Imeson, John; de Kraker, Jan; Jones, David R.

    2005-01-01

    High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma. In this study (European Neuroblastoma Study Group, ENSG1), the value of melphalan myeloablative

  13. 6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia (AML): a randomized trial of the German AML Cooperative Group.

    Science.gov (United States)

    Büchner, Thomas; Hiddemann, Wolfgang; Berdel, Wolfgang E; Wörmann, Bernhard; Schoch, Claudia; Fonatsch, Christa; Löffler, Helmut; Haferlach, Torsten; Ludwig, Wolf-Dieter; Maschmeyer, Georg; Staib, Peter; Aul, Carlo; Gruneisen, Andreas; Lengfelder, Eva; Frickhofen, Norbert; Kern, Wolfgang; Serve, Hubert L; Mesters, Rolf M; Sauerland, Maria Cristina; Heinecke, Achim

    2003-12-15

    To examine the efficacy of prolonged maintenance chemotherapy versus intensified consolidation therapy for patients with acute myeloid leukemia (AML). Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were randomly assigned to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m2 [age or = 60 years] x 6) induction, TAD consolidation, and monthly modified TAD maintenance for 3 years, or TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m2 (age or = 60 years) x 8 instead of maintenance. A total of 69.2% patients went into complete remission (CR). Median relapse-free survival (RFS) was 19 months for patients on the maintenance arm, with 31.4% of patients relapse-free at 5 years, versus 12 months for patients on the S-HAM arm, with 24.7% of patients relapse-free at 5 years (P =.0118). RFS from maintenance was superior in patients with poor risk by unfavorable karyotype, age > or = 60 years, lactate dehydrogenase level greater than 700 U/L, or day 16 bone marrow blasts greater than 40% (P =.0061) but not in patients with good risk by complete absence of any poor risk factors. Although a survival benefit in the CR patients is not significant (P =.085), more surviving patients in the maintenance than in the S-HAM arm remain in first CR (P =.026). We conclude that TAD-HAM-TAD-maintenance first-line treatment has a higher curative potential than TAD-HAM-TAD-S-HAM and improves prognosis even among patients with poor prognosis.

  14. Usefulness of Interim FDG-PET After Induction Chemotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Sequential Induction Chemotherapy Followed by Concurrent Chemoradiotherapy

    International Nuclear Information System (INIS)

    Yoon, Dok Hyun; Cho, Yoojin; Kim, Sang Yoon; Nam, Soon Yuhl; Choi, Seung-Ho; Roh, Jong-Lyel; Lee, Sang-wook; Song, Si Yeol; Lee, Jeong Hyun; Kim, Jae Seung; Cho, Kyung-Ja; Kim, Sung-Bae

    2011-01-01

    Purpose: Induction chemotherapy (ICT) has been used to select patients for organ preservation and determine subsequent treatments in patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN). Still, the clinical outcomes of LASCCHN patients who showed response to ICT are heterogeneous. We evaluated the efficacy of interim 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) after ICT in this specific subgroup of LASCCHN patients who achieved partial response (PR) after ICT to predict clinical outcomes after concurrent chemoradiotherapy (CCRT). Methods and Materials: Twenty-one patients with LASCCHN who showed PR to ICT by Response Evaluation Criteria In Solid Tumors before definitive CCRT were chosen in this retrospective analysis. FDG-PET was performed before and 2-4 weeks after ICT to assess the extent of disease at baseline and the metabolic response to ICT, respectively. We examined the correlation of the metabolic response by the percentage decrease of maximum standardized uptake value (SUVmax) on the primary tumor or lymph node after ICT or a specific threshold of SUVmax on interim FDG-PET with clinical outcomes including complete response (CR) rate to CCRT, progression-free survival (PFS), and overall survival (OS). Results: A SUVmax of 4.8 on interim FDG-PET could predict clinical CR after CCRT (100% vs. 20%, p = 0.001), PFS (median, not reached vs. 8.5 mo, p < 0.001), and OS (median, not reached vs. 12.0 months, p = 0.001) with a median follow-up of 20.3 months in surviving patients. A 65% decrease in SUVmax after ICT from baseline also could predict clinical CR after CCRT (100% vs. 33.3%, p = 0.003), PFS (median, not reached vs. 8.9 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.001) of the patients. Conclusion: These data suggest that interim FDG-PET after ICT might be a useful determinant to predict clinical outcomes in patients with LASCCHN receiving sequential ICT followed by CCRT.

  15. Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study.

    Science.gov (United States)

    Tsuruta, Atsushi; Yamashita, Kazuki; Tanioka, Hiroaki; Tsuji, Akihito; Inukai, Michio; Yamakawa, Toshiki; Yamatsuji, Tomoki; Yoshimitsu, Masanori; Toyota, Kazuhiro; Yamano, Taketoshi; Nagasaka, Takeshi; Okajima, Masazumi

    2016-01-01

    Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC). Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine. Patients with completely resected stage III and high-risk stage II CRC aged ≥20 years were eligible. Patients were treated with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) for 3 months followed by capecitabine (2,500 mg/m 2 on days 1-14 every 3 weeks) for 3 months. Primary end points were frequency and the grade of oxaliplatin-induced neurotoxicity as evaluated using the physician-based Common Terminology Criteria for Adverse Events version 4.0 (CTCAE) grading and the patient-based scale, self-reported Patient Neurotoxicity Questionnaire. Ninety-one patients were enrolled and 86 patients assessed. Eighty-four percent of patients completed the planned oxaliplatin-based therapy for 3 months, and 63% of patients completed all treatments for the full 6 months. Overall incidences of grade 3 or 4 peripheral sensory or motor neuropathy according to the CTCAE were 3.5% and 1.2%, respectively. Regarding the peripheral sensory neuropathy, the proportion of Patient Neurotoxicity Questionnaire (grade C-E) and CTCAE (grade 2-4) at months 1.5/3/6 were 11.3/22.1/29.4% and 5.3/4.4/11.3%, respectively (Spearman correlation coefficient: 0.47). A sequential approach to adjuvant chemotherapy with 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine was tolerated by patients and associated with a low incidence of neuropathy.

  16. The effect of neoadjuvant chemotherapy by sequential paclitaxel and doxorubicin on the interstitial fluid pressure and pO2 in patients with palpable breast cancer

    International Nuclear Information System (INIS)

    Taghian, A.G.; Assaad, S.I.; Molokhia, P.; Raad, R.A.; Yeh, E.; Powell, S.N.; Casty, A.

    2003-01-01

    Tumors with high interstitial fluid pressure (IFP) are thought to respond poorly to chemotherapy (CT) due to poor drug delivery. In addition, a decrease in IFP is hypothesized to improve drug delivery and therefore result in a better response to CT. Pre-clinical studies suggested that Paclitaxel specifically reduces the IFP, with the consequence of improved pO 2 and tumor response to subsequent CT. Evaluate the IFP and pO 2 , using ultrasound guidance, before and after neoadjuvant CT using paclitaxel (P) or doxorubicin (D) in patients with breast cancer of >3cm. Patients were randomized, according to IRB approved protocol, to receive neoadjuvant sequential CT: 4 cycles of dose-dense D (60mg/m 2 / 2 weeks) followed by 9 cycles of P (80 mg/m 2 / week) (D->P arm) or the reverse sequence (P->D arm). Patients were reevaluated clinically and radiologically and IFP (wick-in-needle technique) and pO 2 (Eppendorff) were measured in tumors and in normal tissue at baseline, after completion of the first and the second drug. Forty-two patients have enrolled in the protocol, with 30 of them having completed CT. Fifteen patients were randomized to each arm. The mean IFP at baseline was 7.3 mmHg (range 0.6-17), while in normal tissue 1 mmHg (range -1 to 1.3) (p 2 measurements varied between 1.6 and 49.4 mmHg with overall mean of 22 mmHg. The median pO 2 in normal tissue was 45 mmHg (range 26-55) (p=0.0002. In the P->D arm, the mean IFP at baseline and after P were 7.3 mmHg and 4.6 mmHg, respectively (p=0.01). The mean pO 2 in this group before and after P was 13.2 and 27.0 mmHg, respectively (p=0.01). In the D->P arm, the mean IFP at baseline and after D were 6.6 mmHg and 5.2 mmHg, respectively (p=NS). The mean pO 2 at baseline and after D was 19.6 and 13.7 mmHg, respectively (p=0.38). These preliminary data showed that Paclitaxel significantly decreased the IFP and increased the pO 2 , whereas doxorubicin did not change the IFP and had a tendency to decrease the pO 2 . These

  17. Prognostic impact of hemoglobin level and other factors in patients with high-grade gliomas treated with postoperative radiochemotherapy and sequential chemotherapy based on temozolomide. A 10-year experience at a single institution

    International Nuclear Information System (INIS)

    Ausili Cefaro, Giampiero; Genovesi, Domenico; Vinciguerra, Annamaria; Trignani, Marianna; Taraborrelli, Maria; Augurio, Antonietta; Buonaguidi, Roberto; Galzio, Renato J.; Di Nicola, Marta

    2011-01-01

    To evaluate the influence of serum hemoglobin level prior to radiotherapy and other prognostic factors on survival in patients with high-grade gliomas. From 2001-2010, we retrospectively evaluated a total of 48 patients with malignant glioma treated with surgery and postoperative radiochemotherapy with temozolomide. A total of 37 of 48 patients received sequential temozolomide. Hemoglobin levels were assayed before radiotherapy in all patients. The Kaplan-Meier method was applied to estimate the overall survival, while the log-rank test was applied to evaluate the differences on survival probability between prognostic subgroups. Results were assessed in 43 patients. The median overall survival time was 18 months (95% confidence interval: 12-40 months). The 1- and 2-year survival rates were 62.2% and 36.3%, respectively. The prognostic factors analyzed were gender, age, extent of surgery, performance status before and after radiotherapy, sequential chemotherapy, hemoglobin level, and methylation of the O-6-methylguanine-DNA methyltransferase gene (MGMT). In univariate analysis, the variables significantly related to survival were performance status before and after radiotherapy, sequential chemotherapy, and hemoglobin level. The median overall survival in patients with a hemoglobin level ≤ 12 g/dl was 12 months and 23 months in patients with a hemoglobin level > 12 g/dl. The 1- and 2-year survival rates were 46.7% and 20.0%, respectively, for patients with a hemoglobin level ≤ 12 mg/dl and 69.6% and 45.7%, respectively, for patients with a hemoglobin level > 12 g/dl. Our results confirm the impact of well-known prognostic factors on survival. In this research, it was found that a low hemoglobin level before radiotherapy can adversely influence the prognosis of patients with malignant gliomas.

  18. A prospective and randomized study of radiotherapy, sequential chemotherapy radiotherapy and concomitant chemo therapy-radiotherapy in unresectable non small cell carcinoma of the lung

    Directory of Open Access Journals (Sweden)

    Dasgupta Anirban

    2006-01-01

    Full Text Available Purpose: Treatment of advanced Non small cell lung cancer (NSCLC often produces dismal results. Combination of available treatment modalities has reportedly improved the outcome. A prospectively randomized trial was conducted, comparing combined treatment modalities versus radiotherapy alone, in treatment of unresectable NSCLC. Materials and Methods: A total of 103 patients were randomized to three groups. In group ′A′, 32 patients received radiotherapy alone (6500 cGy/30 fraction. In group ′B′, 35 patients received neoadjuvant chemotherapy (Cisplatin 80 mg/m2 on day 1 and Etoposide 100 mg/m day 1-3 intravenously q3 weeks for 3 cycles, followed by radiotherapy (6000 cGy/30 fractions and 3 more cycles of Chemotherapy, with the same regimen. In group ′C′, 36 patients received radiotherapy (5000 cGy/25 fractions with concurrent chemotherapy (ciplatin 20 mg/m2 + Etoposide 75 mg/m2 intravenously on day 1-5 and day 22-26, followed by 2 more cycles of chemotherapy,q3 weeks with the same regimen. Results: Initial treatment responses were significantly higher in group ′B′ ( P P Conclusion: Addition of chemotherapy with radiation in unresectable NSCLC improves response rates, time to tumour progression and disease free survival, though the same effect is not translated in overall survival.

  19. Sequential functional imaging with technetium-99m hexakis-2-methoxyisobutylisonitrile and indium-111 octreotide: can we predict the response to chemotherapy in small cell lung cancer?

    International Nuclear Information System (INIS)

    Moretti, J.L.; Caglar, M.; Boaziz, C.; Caillat-Vigneron, N.; Morere, J.F.

    1995-01-01

    A case of small cell lung carcinoma (SCLC) demonstrating uptake on functional indium-111 octreotide scintigraphy is presented. Technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI) scintigraphy clearly delineated an absence of radionuclide uptake at the tumour site. This suggested the presence of multidrug resistance-mediated P glycoprotein (Pgp) on tumour cells, which recognizes certain chemotherapeutic agents as well as MIBI as a substrate and avoids radionuclide concentration. Following three courses of chemotherapy, the patient failed to improve and eventually died. This case demonstrates the importance of functional images, which have the potential to predict the outcome in response to chemotherapy. (orig.)

  20. Concomitant chemoradiotherapy with high dose rate brachytherapy ...

    African Journals Online (AJOL)

    Concomitant chemoradiotherapy with high dose rate brachytherapy as a definitive treatment modality for locally advanced cervical cancer. T Refaat, A Elsaid, N Lotfy, K Kiel, W Small Jr, P Nickers, E Lartigau ...

  1. Fiber optics in high dose radiation fields

    International Nuclear Information System (INIS)

    Partin, J.K.

    1985-01-01

    A review of the behavior of state-of-the-art optical fiber waveguides in high dose (greater than or equal to 10 5 rad), steady state radiation fields is presented. The influence on radiation-induced transmission loss due to experimental parameters such as dose rate, total dose, irradiation history, temperature, wavelength, and light intensity, for future work in high dose environments are given

  2. Sequential FDG-PET and induction chemotherapy in locally advanced adenocarcinoma of the Oesophago-gastric junction (AEG): The Heidelberg Imaging program in Cancer of the oesophago-gastric junction during Neoadjuvant treatment: HICON trial

    International Nuclear Information System (INIS)

    Lorenzen, Sylvie; Debus, Jürgen; Jäger, Dirk; Münter, Marc W; Gall, Carl von; Stange, Annika; Haag, Georg M; Weitz, Jürgen; Haberkorn, Uwe; Lordick, Florian; Weichert, Wilko; Abel, Ulrich

    2011-01-01

    will be calculated and assessed as an early predictor of histopathological response. In a secondary analysis, the association between the difference SUV PET1 - SUV PET2 and histopathological response will be evaluated. The aim of this study is to investigate the potential of sequential 18 FDG-PET in predicting histopathological response in AEG tumors to salvage neoadjuvant radiochemotherapy in patients who do not show metabolic response to standard neoadjuvant chemotherapy. Clinical trial identifier http://www.clinicaltrials.gov/ct2/show/NCT01271322

  3. CpG island methylator phenotype is associated with the efficacy of sequential oxaliplatin- and irinotecan-based chemotherapy and EGFR-related gene mutation in Japanese patients with metastatic colorectal cancer.

    Science.gov (United States)

    Zhang, Xiaofei; Shimodaira, Hideki; Soeda, Hiroshi; Komine, Keigo; Takahashi, Hidekazu; Ouchi, Kota; Inoue, Masahiro; Takahashi, Masanobu; Takahashi, Shin; Ishioka, Chikashi

    2016-12-01

    The CpG island methylator phenotype (CIMP) with multiple promoter methylated loci has been observed in a subset of human colorectal cancer (CRC) cases. CIMP status, which is closely associated with specific clinicopathological and molecular characteristics, is considered a potential predictive biomarker for efficacy of cancer treatment. However, the relationship between the effect of standard chemotherapy, including cytotoxic drugs and anti-epidermal growth factor receptor (EGFR) antibodies, and CIMP status has not been elucidated. In 125 metastatic colorectal cancer (mCRC) patients, we investigated how clinical outcome of chemotherapy was related to CIMP status as detected by methylation-specific PCR (MSP) and to genetic status in five EGFR-related genes (KRAS, BRAF, PIK3CA, NRAS, and AKT1) as detected by direct sequencing. CIMP-positive status was significantly associated with proximal tumor location and peritoneum metastasis (all P values CIMP-positive tumors receiving sequential therapy with FOLFOX as the first-line treatment followed by irinotecan-based therapy as the second-line treatment (median = 6.6 months) was inferior to that of such patients receiving the reverse sequence (median = 15.2 months; P = 0.043). Furthermore, CIMP-positive tumors showed higher mutation frequencies for the five EGFR-related genes (74.1 %) than the CIMP-negative tumors did (50.0 %). Among the KRAS wild-type tumors, CIMP-positive tumors were associated with a worse clinical outcome than CIMP-negative tumors following anti-EGFR antibody therapy. Sequential FOLFOX followed by an irinotecan-based regimen is unfavorable in patients with CIMP-positive tumors. High frequencies of mutation in EGFR-related genes in CIMP-positive tumors may cause the lower response to anti-EGFR antibody therapy seen in patients with wild-type KRAS and CIMP-positive tumors.

  4. Sequential FDG-PET and induction chemotherapy in locally advanced adenocarcinoma of the Oesophago-gastric junction (AEG: The Heidelberg Imaging program in Cancer of the oesophago-gastric junction during Neoadjuvant treatment: HICON trial

    Directory of Open Access Journals (Sweden)

    Weichert Wilko

    2011-06-01

    SUVPET1 - SUVPET2 and histopathological response will be evaluated. Discussion The aim of this study is to investigate the potential of sequential 18FDG-PET in predicting histopathological response in AEG tumors to salvage neoadjuvant radiochemotherapy in patients who do not show metabolic response to standard neoadjuvant chemotherapy. Trial Registration Clinical trial identifier NCT01271322

  5. Progress in high-dose radiation dosimetry

    International Nuclear Information System (INIS)

    Ettinger, K.V.; Nam, J.W.; McLaughlin, W.L.; Chadwick, K.H.

    1981-01-01

    The last decade has witnessed a deluge of new high-dose dosimetry techniques and expanded applications of methods developed earlier. Many of the principal systems are calibrated by means of calorimetry, although production of heat is not always the final radiation effect of interest. Reference systems also include a number of chemical dose meters: ferrous sulphate, ferrous-cupric sulphate, and ceric sulphate acidic aqueous solutions. Requirements for stable and reliable transfer dose meters have led to further developments of several important high-dose systems: amino acids and saccharides analysed by ESR or lyoluminescence, thermoluminescent materials, radiochromic dyes and plastics, ceric-cerous solutions analysed by potentiometry, and ethanol-chlorobenzene solutions analysed by high-frequency oscillometry. A number of other prospective dose meters are also treated in this review. In addition, an IAEA programme of high-dose standardization and intercomparison for industrial radiation processing is described. (author)

  6. Intracranial meningiomas after high-dose irradiation

    International Nuclear Information System (INIS)

    Soffer, D.; Gomori, J.M.; Siegal, T.; Shalit, M.N.

    1989-01-01

    Three patients who presented with intracranial meningiomas 12, 15, and 20 years, respectively, after therapeutic high-dose irradiation of a primary brain tumor are described. Analysis of these cases and similar documented cases suggests that meningiomas after high-dose irradiation constitute a recognizable entity. Patients with such tumors received radiation therapy at a young age (mean age, 9.4 years). After a latent period of 2 to 47 years (mean, 19.8 years) they developed meningiomas at the site of irradiation, at a much younger age than patients with ''spontaneous'' meningiomas. Similar to the situation with meningiomas after low-dose irradiation, a relatively high proportion of meningiomas induced by high-dose irradiation tend to be malignant and biologically aggressive. A very young age at the time of irradiation seems to predispose to the induction of malignant meningiomas, rather than benign tumors. These unusual features provide indirect evidence that high-dose radiation may play a role in the pathogenesis of meningiomas.41 references

  7. Endorectal high dose rate brachytherapy quality assurance

    International Nuclear Information System (INIS)

    Devic, S.; Vuong, T.; Evans, M.; Podgorsak, E.

    2008-01-01

    We describe our quality assurance method for preoperative high dose rate (HDR) brachytherapy of endorectal tumours. Reproduction of the treatment planning dose distribution on a daily basis is crucial for treatment success. Due to the cylindrical symmetry, two types of adjustments are necessary: applicator rotation and dose distribution shift along the applicator axis. (author)

  8. Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study

    Directory of Open Access Journals (Sweden)

    Tsuruta A

    2016-11-01

    Full Text Available Atsushi Tsuruta,1,* Kazuki Yamashita,2,* Hiroaki Tanioka,3 Akihito Tsuji,4,5 Michio Inukai,6 Toshiki Yamakawa,7 Tomoki Yamatsuji,8 Masanori Yoshimitsu,9 Kazuhiro Toyota,10 Taketoshi Yamano,11 Takeshi Nagasaka,12 Masazumi Okajima13 On behalf of the Japan Southwest Oncology Group (JSWOG 1Department of Digestive Surgery, Kawasaki Medical School Hospital, 2Department of Surgery, 3Department of Medical Oncology, Okayama Rosai Hospital, Okayama, 4Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, 5Department of Clinical Oncology, Faculty of Medicine, Kagawa University Hospital, Kagawa, 6Department of Medicine, Okayama Saiseikai General Hospital, Okayama, 7Department of Surgery, Kagawa Prefectural Central Hospital, Takamatsu, 8Department of General Surgery, Kawasaki Medical School, Okayama, 9Department of Surgery, Hiroshima City Asa Hospital, Hiroshima, 10Department of Surgery, National Hospital Organization Higashihirosima Medical Center, Higashihiroshima, 11Department of Surgery, Kurashiki Medical Center, 12Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 13Department of Surgery, Hiroshima City Hospital, Hiroshima, Japan *These authors contributed equally to this work Background: Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC. Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine. Patients and methods: Patients with completely resected stage III and high-risk stage II CRC aged ≥20 years were

  9. Sequential versus "sandwich" sequencing of adjuvant chemoradiation for the treatment of stage III uterine endometrioid adenocarcinoma.

    Science.gov (United States)

    Lu, Sharon M; Chang-Halpenny, Christine; Hwang-Graziano, Julie

    2015-04-01

    To compare the efficacy and tolerance of adjuvant chemotherapy and radiotherapy delivered in sequential (chemotherapy followed by radiation) versus "sandwich" fashion (chemotherapy, interval radiation, and remaining chemotherapy) after surgery in patients with FIGO stage III uterine endometrioid adenocarcinoma. From 2004 to 2011, we identified 51 patients treated at our institution fitting the above criteria. All patients received surgical staging followed by adjuvant chemoradiation (external-beam radiation therapy (EBRT) with or without high-dose rate (HDR) vaginal brachytherapy (VB)). Of these, 73% and 27% of patients received their adjuvant therapy in sequential and sandwich fashion, respectively. There were no significant differences in clinical or pathologic factors between patients treated with either regimen. Thirty-nine (76%) patients had stage IIIC disease. The majority of patients received 6 cycles of paclitaxel with carboplatin or cisplatin. Median EBRT dose was 45 Gy and 54% of patients received HDR VB boost (median dose 21 Gy). There were no significant differences in the estimated 5-year overall survival, local progression-free survival, and distant metastasis-free survival between the sequential and sandwich groups: 87% vs. 77% (p=0.37), 89% vs. 100% (p=0.21), and 78% vs. 85% (p=0.79), respectively. No grade 3-4 genitourinary or gastrointestinal toxicities were reported in either group. There was a trend towards higher incidence of grade 3-4 hematologic toxicity in the sandwich group. Adjuvant chemoradiation for FIGO stage III endometrioid uterine cancer given in either sequential or sandwich fashion appears to offer equally excellent early clinical outcomes and acceptably low toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Improved survival of multiple myeloma patients with late relapse after high-dose treatment and stem cell support, a population-based study of 348 patients in Denmark in 1994-2004

    DEFF Research Database (Denmark)

    Vangsted, Annette Juul; Klausen, Tobias W; Andersen, Niels F

    2010-01-01

    To analyse if patients with early relapse after high-dose chemotherapy with stem cell support (HDT) benefit from new treatment strategies in a population-based setting.......To analyse if patients with early relapse after high-dose chemotherapy with stem cell support (HDT) benefit from new treatment strategies in a population-based setting....

  11. High-dose irradiation of food

    International Nuclear Information System (INIS)

    Diehl, J.F.

    1999-01-01

    Studies performed on behalf of the International Project on Food Irradiation in the period from 1971 until 1980 resulted in the concluding statement that ''.the irradiation of any food commodity up to an overall average dose of 10 kGy presents no toxicological hazard; hence, toxicological testing of foods so treated is no longer required.'' Since then, licenses for food irradiation have been restricted to this maximum dose in any country applying this technology. Further testing programmes have been carried out investigating the wholesomeness or hazards of high-dose irradiation, but there has been little demand so far by the food industry for licensing of high-dose irradiation, as there is only a small range of products whose irradiation at higher doses offers advantages for given, intended use. These include eg. spices, dried herbs, meat products in flexible pouch packagings for astronauts, or patients with immune deficiencies. (orig./CB) [de

  12. High-dose erythropoietin for tissue protection

    DEFF Research Database (Denmark)

    Lund, Anton; Lundby, Carsten; Olsen, Niels Vidiendal

    2014-01-01

    BACKGROUND: The discovery of potential anti-apoptotic and cytoprotective effects of recombinant human erythropoietin (rHuEPO) has led to clinical trials investigating the use of high-dose, short-term rHuEPO therapy for tissue protection in conditions such as stroke and myocardial infarction....... Experimental studies have been favourable, but the clinical efficacy has yet to be validated. MATERIALS AND METHODS: We have reviewed clinical studies regarding the use of high-dose, short-term rHuEPO therapy for tissue protection in humans with the purpose to detail the safety and efficacy of r...... no effect of rHuEPO therapy on measures of tissue protection. Five trials including 1025 patients reported safety concerns in the form of increased mortality or adverse event rates. No studies reported reduced mortality. CONCLUSIONS: Evidence is sparse to support a tissue-protective benefit of r...

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

    Directory of Open Access Journals (Sweden)

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

    2011-01-01

    Full Text Available 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.

  14. Sequential chemotherapy with dose-dense docetaxel, cisplatin, folinic acid and 5-fluorouracil (TCF-dd) followed by combination of oxaliplatin, folinic acid, 5-fluorouracil and irinotecan (COFFI) in metastatic gastric cancer: results of a phase II trial.

    Science.gov (United States)

    Dalla Chiesa, Matteo; Tomasello, Gianluca; Buti, Sebastiano; Rovere, Rodrigo Kraft; Brighenti, Matteo; Lazzarelli, Silvia; Donati, Gianvito; Passalacqua, Rodolfo

    2011-01-01

    To evaluate a new strategy of two sequential, intensified chemotherapy regimens in metastatic gastric cancer. Chemo-naïve patients with metastatic gastric cancer were enrolled to receive 4 cycles of TCF-dd (docetaxel initially 85 mg/m(2) and cisplatin initially 75 mg/m(2) on day 1 [later modified due to toxicity: 70 and 60 mg/m(2) respectively], l-folinic acid 100 mg/m(2) on days 1 and 2, 5-fluorouracil 400 mg/m(2) bolus and then 600 mg/m(2) as a 22 h continuous infusion on day 1 and 2, every 14 days). Subsequently, patients with CR, PR or SD received 4 cycles of COFFI (oxaliplatin 85 mg/m(2), irinotecan 140 mg/m(2), l-folinic acid 200 mg/m(2), 5-fluorouracil bolus 400 mg/m(2) on day 1 followed by 2,400 mg/m(2) as a 48 h continuous infusion, every 14 days). In both regimens pegfilgrastim 6 mg subcutaneously on day 3 was included. Forty consecutive patients were enrolled. TCF-dd regimen achieved an ORR of 55% (95% CI, 40-70). Twenty-three patients proceeded to COFFI. After this regimen the ORR was then increased to 60% (95% CI, 45-75). Among the 21 patients treated with TCF-dd after the protocol amendments, main grade 3-4 toxicities were: neutropenia (29%), thrombocytopenia (19%), asthenia (24%) and diarrhea (14%). COFFI caused grade 3-4 neutropenia (all not febrile) and diarrhea in 35% and 17% of patients respectively. A sequential strategy with TCF-dd followed by COFFI is very active and may be of special interest in selected patients.

  15. Combined radiotherapy and chemotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Inuyama, Yukio; Fujii, Masato; Tanaka, Juichi; Takaoka, Tetsuro; Hosoda, Hyonosuke; Kawaura, Mitsuhiro; Toji, Masao

    1988-01-01

    There are 4 modalities of combined radiotherapy and chemotherapy which include (1) concurrent radiotherapy and chemotherapy, (2) sequential use of radiotherapy and chemotherapy (pre-radiation chemotherapy), (3) pre-radiation chemotherapy followed by concurrent radiation and chemotherapy, and (4) alternating use of radiotherapy and chemotherapy based upon Looney's hypothesis. We studied concurrent use of radiotherapy and UFT by means of animal experimentation and clinical trials. The results obtained revealed that UFT was a most suitable agent together with 5-fluorouracil for concurrent application of radiotherapy and chemotherapy. Neo-adjuvant chemotherapy including pre-radiation chemotherapy was also studied in cases of maxillary sinus carcinoma and nasopharyngeal carcinoma. From the results, it seemed desirable to use cisplatin and bleomycin analogs sequentially in combined chemotherapy and radiotherapy. Neo-adjuvant chemotherapy should be studied successively to improve local tumor control rates and prevent distant metastases. For future perspectives, new trials of alternating radiotherapy and chemotherapy based upon Looney's hypothesis seem necessary. (author)

  16. High dose rate endobronchial brachytherapy - treatment technique

    International Nuclear Information System (INIS)

    Carvalho, Heloisa de Andrade; Aisen, Salim; Haddad, Cecilia Maria Kalil; Nadalin, Wladimir; Pedreira Junior, Wilson Leite; Chavantes, Maria Cristina

    1998-01-01

    High dose rate endobronchial brachytherapy is efficient in symptom relief due to obstructive endobronchial malignancies. However, it's role in survival improvement for patients with lung cancer is not yet established. The use of this treatment in increasing, specially in the developing countries. The purpose of this paper is to present the treatment technique used in the Radiotherapy Department of the Hospital da Clinicas, University of Sao Paulo, based on an experience of 60 cases treated with 180 procedures. Some practical suggestions and rules adopted in the Department are described. The severe complications rate is 6.7%, demonstrating an adequate patient selection associated with the technique utilized. (author)

  17. Neuroprotective potential of high-dose biotin.

    Science.gov (United States)

    McCarty, Mark F; DiNicolantonio, James J

    2017-11-01

    A recent controlled trial has established that high-dose biotin supplementation - 100 mg, three times daily - has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS. But biotin's ability to boost cGMP synthesis in the brain may have broader neuroprotective potential. In many types of neurons and neural cells, cGMP exerts neurotrophic-mimetic effects - entailing activation of the PI3K-Akt and Ras-ERK pathways - that promote neuron survival and plasticity. Hippocampal long term potentiation requires nitric oxide synthesis, which in turn promotes an activating phosphorylation of CREB via a pathway involving cGMP and protein kinase G (PKG). In Alzheimer's disease (AD), amyloid beta suppresses this mechanism by inhibiting sGC activity; agents which exert a countervailing effect by boosting cGMP levels tend to restore effective long-term potentiation in rodent models of AD. Moreover, NO/cGMP suppresses amyloid beta production within the brain by inhibiting expression of amyloid precursor protein and BACE1. In conjunction with cGMP's ability to oppose neuron apoptosis, these effects suggest that high-dose biotin might have potential for the prevention and management of AD. cGMP also promotes neurogenesis, and may lessen stroke risk by impeding atherogenesis and hypertrophic remodeling in the cerebral vasculature. The neuroprotective potential of high-dose biotin likely could be boosted by concurrent administration of brain

  18. Systemic high-dose methotrexate plus ifosfamide is highly effective for central nervous system (CNS) involvement of lymphoma

    OpenAIRE

    2008-01-01

    Abstract Patients with malignant central nervous system (CNS) involvement of lymphoma have a poor prognosis with intrathecal chemotherapy and radiation. In this paper, we report the results we obtained in such patients by intravenous chemotherapy with high-dose methotrexate and ifosfamide (HDMTX/IFO). The study involved a review of all patients who received HDMTX/IFO for CNS involvement of malignant lymphoma at our hospital. Therapy consisted of 4 g/m2 of MTX (4 h infu...

  19. Assessments for high dose radionuclide therapy treatment planning

    International Nuclear Information System (INIS)

    Fisher, D.R.

    2003-01-01

    Advances in the biotechnology of cell specific targeting of cancer and the increased number of clinical trials involving treatment of cancer patients with radiolabelled antibodies, peptides, and similar delivery vehicles have led to an increase in the number of high dose radionuclide therapy procedures. Optimised 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 the 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 timepoints using a planar gamma camera. Time-activity curves are developed from the imaging data for the major organ tissues of concern, for the whole body and sometimes for selected tumours. Patient specific factors often require that dose estimates be customised for each patient. In the United States, 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 the methods prescribed by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. Review of high dose studies shows that some are conducted with minimal dosimetry, that the marrow dose is difficult to establish and is subject to large uncertainties. Despite the general availability of software, internal dosimetry methods often seem to be inconsistent from one clinical centre to another. (author)

  20. Immune reactivity after high-dose irradiation

    International Nuclear Information System (INIS)

    Gassmann, W.; Wottge, H.U.; von Kolzynski, M.; Mueller-Ruchholtz, W.

    1986-01-01

    Immune reactivity after total-body irradiation was investigated in rats using skin graft rejection as the indicator system. After sublethal irradiation with 10.5 Gy (approximately 50% lethality/6 weeks) the rejection of major histocompatibility complex allogeneic skin grafts was delayed significantly compared with nonirradiated control animals (28 versus 6.5 days). In contrast, skin grafts were rejected after 7.5 days in sublethally irradiated animals and 7 days in lethally irradiated animals if additional skin donor type alloantigens--namely, irradiated bone marrow cells--were given i.v. either simultaneously or with a delay of not more than 24 hr after the above conditioning regimen. These reactions were alloantigen-specific. They were observed in six different strain combinations with varying donors and recipients. Starting on day 2 after irradiation, i.v. injection of bone marrow gradually lost its effectivity and skin grafts were no longer rejected with uniform rapidity; skin donor marrow given on days 4 or 8 did not accelerate skin graft rejection at all. These data show that for approximately 1-2 days after high-dose total-body irradiation rats are still capable of starting a vigorous immune reaction against i.v.-injected alloantigens. The phenomenon of impaired rejection of skin grafted immediately after high-dose irradiation appears to result from the poor accessibility of skin graft alloantigens during the early postirradiation phase when vascularization of the grafted skin is insufficient

  1. High-dose vitamin C and cancer

    Directory of Open Access Journals (Sweden)

    Ahmet Unlu, M.D.

    2016-01-01

    Full Text Available Vitamin C (ascorbic acid, ascorbate is a basic compound that is of great importance with its role in various enzymatic reactions including the synthesis of collagen, as well as with its redox functions. Vitamin C has become the center of interest in cancer studies, in consequence of the facts that connective tissue changes and vitamin C deficiency were first alleged to be associated with cancer in the 1950s; and that high doses of vitamin C was asserted to be cytotoxic for cancer cells, later on. The results of the first study carried out in the 1970s were promising; but afterwards, the studies were ascertained to be faulty. Despite the positive results achieved from some laboratory and animal experiments, randomized clinical trials did not verify those findings, and no clear benefit of vitamin C for cancer treatment could be demonstrated. As for studies, where its use in combination with other cancer treatment regimens was assessed, conflicting results were obtained. Although intake of high doses of vitamin C is alleged to be harmless, based on that it is in the group of water soluble vitamins and is not stored in the body, there are many side effects and drug interactions reported in the literature. For now, it is better to abstain from this treatment, until the benefit of the treatment (if any is clearly demonstrated, considering the potential side effects and interactions.

  2. NIST high-dose calibration services

    International Nuclear Information System (INIS)

    Humphreys, J.C.

    1989-01-01

    There is a need for the standardization of high-dose measurements used in the radiation-processing industry in order to provide assured traceability to national standards. NIST provides dosimetry calibration services to this industry. One of these services involves administration of known absorbed doses of gamma rays to customer-supplied dosimeters. The dosimeters are packaged to provide electron equilibrium conditions and are irradiated in a standard 60 Co calibration facility; this provides a calibration of that batch of dosimeters. Another service consists of supplying to a customer calibrated transfer dosimeters for irradiation with the customer's radiation source. The irradiated transfer dosimeters are then returned to NIST for analysis; the results are reported to the customer, providing a calibration of the dose rate of the customer's source. (orig.)

  3. Onyx as radiation detector for high doses

    International Nuclear Information System (INIS)

    Teixeira, Maria Inês; Souza, Divanizia N.; Caldas, Linda V.E.

    2011-01-01

    A study of the thermoluminescent (TL) characteristics of white, black and stripped onyx samples is reported in this work. Onyx is a variety of chalcedony, a form of quartz. The onyx stone is considered nobler than marble. The irradiations were performed using a Gamma-Cell 220 system ( 60 Co). The TL emission curves presented two peaks around 150 °C and 210 °C for all samples. The dose–response curves showed a sublinear behavior between 0.5 Gy and 5 kGy, and the lower detection limit for the white onyx pellets was 1.5 mGy. The main dosimetric characteristics were studied, and the material showed good performance for high dose dosimetry.

  4. Nonlinear model of high-dose implantation

    International Nuclear Information System (INIS)

    Danilyuk, A.

    2001-01-01

    The models of high-dose implantation, using the distribution functions, are relatively simple. However, they must take into account the variation of the function of distribution of the implanted ions with increasing dose [1-4]. This variation takes place owing to the fact that the increase of the concentration of the implanted ions results in a change of the properties of the target. High-dose implantation is accompanied by sputtering, volume growth, diffusion, generation of defects, formation of new phases, etc. The variation of the distribution function is determined by many factors and is not known in advance. The variation within the framework of these models [1-4] is taken into account in advance by the introduction of intuitive assumptions on the basis of implicit considerations. Therefore, these attempts should be regarded as incorrect. The model prepared here makes it possible to take into account the sputtering of the target, volume growth and additional declaration on the implanted ions. Without any assumptions in relation to the variation of the distribution function with increasing dose. In our model it is assumed that the type of distribution function for small doses in a pure target substance is the same as in substances with implanted ions. A second assumption relates to the type of the distribution function valid for small doses in the given substances. These functions are determined as a result of a large number of theoretical and experimental investigations and are well-known at the present time. They include the symmetric and nonsymmetric Gauss distribution, the Pearson distribution, and others. We examine implantation with small doses of up to 10 14 - 10 15 cm -2 when the accurately known distribution is valid

  5. Ionization chamber for high dose measurements

    International Nuclear Information System (INIS)

    Rodrigues Junior, Ary de Araujo

    2005-01-01

    Industrial gamma irradiators facilities are designed for processing large amounts of products, which are exposed to large doses of gamma radiation. The irradiation, in industrial scale, is usually carried out in a dynamic form, where the products go through a 60 Co gamma source with activity of TBq to P Bq (k Ci to MCi). The dose is estimated as being directly proportional to the time that the products spend to go through the source. However, in some situations, mainly for research purposes or for validation of customer process following the ISO 11137 requirements, it is required to irradiate small samples in a static position with fractional deliver doses. The samples are put inside the irradiation room at a fixed distance from the source and the dose is usually determined using dosimeters. The dose is only known after the irradiation, by reading the dosimeter. Nevertheless, in the industrial irradiators, usually different kinds of products with different densities go through between the source and the static position samples. So, the dose rate varies in function of the product density. A suitable methodology would be to monitor the samples dose in real time, measuring the dose on line with a radiation detector, which would improve the dose accuracy and avoid the overdose. A cylindrical ionization chamber of 0.9 cm 3 has been developed for high-doses real-time monitoring, during the sample irradiation at a static position in a 60 Co gamma industrial plant. Nitrogen and argon gas at pressure of 10 exp 5 Pa (1 bar) was utilized to fill the ionization chamber, for which an appropriate configuration was determined to be used as a detector for high-dose measurements. To transmit the signal generated in the ionization chamber to the associated electronic and processing unit, a 20 m mineral insulated cable was welded to the ionization chamber. The signal to noise ratio produced by the detector was about 100. The dosimeter system was tested at a category I gamma

  6. High dose rate brachytherapy for oral cancer

    International Nuclear Information System (INIS)

    Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Koizumi, Masahiko; Ogawa, Kazuhiko; Furukawa, Souhei

    2013-01-01

    Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer. (author)

  7. High dose rate brachytherapy for oral cancer.

    Science.gov (United States)

    Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Furukawa, Souhei; Koizumi, Masahiko; Ogawa, Kazuhiko

    2013-01-01

    Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.

  8. High dose gamma-ray standard

    International Nuclear Information System (INIS)

    Macrin, R.; Moraru, R.

    1999-01-01

    The high gamma-ray doses produced in a gamma irradiator are used, mainly, for radiation processing, i.e. sterilization of medical products, processing of food, modifications of polymers, irradiation of electronic devices, a.s.o. The used absorbed doses depend on the application and cover the range 10 Gy to 100 MGy. The regulations in our country require that the response of the dosimetry systems, used for the irradiation of food and medical products, be calibrated and traceable to the national standards. In order to be sure that the products receive the desired absorbed dose, appropriate dosimetric measurements must be performed, including the calibration of the dosemeters and their traceability to the national standards. The high dose gamma-ray measurements are predominantly based on the use of reference radiochemical dosemeters. Among them the ferrous sulfate can be used as reference dosemeter for low doses (up to 400 Gy) but due to its characteristics it deserves to be considered a standard dosemeter and to be used for transferring the conventional absorbed dose to other chemical dosemeters used for absorbed doses up to 100 MGy. The study of the ferrous sulfate dosemeter consisted in preparing many batches of solution by different operators in quality assurance conditions and in determining for all batches the linearity, the relative intrinsic error, the repeatability and the reproducibility. The principal results are the following: the linear regression coefficient: 0.999, the relative intrinsic error: max.6 %, the repeatability (for P* = 95 %): max.3 %, the reproducibility (P* = 95%): max.5 %. (authors)

  9. Can high-dose fotemustine reverse MGMT resistance in glioblastoma multiforme?

    Science.gov (United States)

    Gallo, Chiara; Buonerba, Carlo; Di Lorenzo, Giuseppe; Romeo, Valeria; De Placido, Sabino; Marinelli, Alfredo

    2010-11-01

    Glioblastoma multiforme (GBM), the highest grade malignant glioma, is associated with a grim prognosis-median overall survival is in the range 12-15 months, despite optimum treatment. Surgery to the maximum possible extent, external beam radiotherapy, and systemic temozolomide chemotherapy are current standard treatments for newly diagnosed GBM, with intracerebral delivery of carmustine wafers (Gliadel). Unfortunately, the effectiveness of chemotherapy can be hampered by the DNA repair enzyme O6-methylguanine methyltransferase (MGMT), which confers resistance both to temozolomide and nitrosoureas, for example fotemustine and carmustine. MGMT activity can be measured by PCR and immunohistochemistry, with the former being the current validated technique. High-dose chemotherapy can deplete MGMT levels in GBM cells and has proved feasible in various trials on temozolomide, in both newly diagnosed and recurrent GBM. We here report the unique case of a GBM patient, with high MGMT expression by immunohistochemistry, who underwent an experimental, high-dose fotemustine schedule after surgery and radiotherapy. Although treatment caused two episodes of grade 3-4 thrombocytopenia, a complete response and survival of more than three years were achieved, with a 30% increase in dose intensity compared with the standard fotemustine schedule.

  10. High-dose radiation-induced meningioma following prophylactic cranial irradiation for acute lymphoblastic leukaemia

    International Nuclear Information System (INIS)

    Matsuda, Ryosuke; Nikaido, Yuji; Yamada, Tomonori; Mishima, Hideaki; Tamaki, Ryo

    2005-01-01

    A 12 year-old girl was treated with prophylactic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylactic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed. (author)

  11. High-dose radiation-induced meningioma following prophylactic cranial irradiation for acute lymphoblastic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Matsuda, Ryosuke; Nikaido, Yuji; Yamada, Tomonori; Mishima, Hideaki; Tamaki, Ryo [National Hospital Organization Osaka Minami Medical Center, Kawachinagano (Japan)

    2005-03-01

    A 12 year-old girl was treated with prophylactic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylactic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed. (author)

  12. Performance of thermoluminescent materials for high dose dosimetry

    International Nuclear Information System (INIS)

    Texeira, Maria I.; Cecatti, Sonia G.P.; Caldas, Linda V.E.

    2008-01-01

    Cases involving high-doses of ionizing radiation are becoming increasingly common.The objective of this work was to characterize thermoluminescent materials for the dosimetry of workers exposed to high doses. Samples of TLD-200, TLD-400 and TLD-800 pellets from Thermo Electron Corporation were studied in gamma high-doses. Dose-response curves were obtained for doses between 100 mGy and 100 Gy. The reproducibility, the lower detection limits and dose-response curves were obtained for all three materials. The different kinds of detectors show usefulness for dosimetry of workers exposed accidentally to high doses. (author)

  13. Sequential Banking.

    OpenAIRE

    Bizer, David S; DeMarzo, Peter M

    1992-01-01

    The authors study environments in which agents may borrow sequentially from more than one leader. Although debt is prioritized, additional lending imposes an externality on prior debt because, with moral hazard, the probability of repayment of prior loans decreases. Equilibrium interest rates are higher than they would be if borrowers could commit to borrow from at most one bank. Even though the loan terms are less favorable than they would be under commitment, the indebtedness of borrowers i...

  14. Palonosetron for the prevention of nausea and vomiting in children with acute lymphoblastic leukemia treated with high dose methotrexate

    DEFF Research Database (Denmark)

    Nadaraja, Sambavy; Mamoudou, Aissata Diop; Thomassen, Harald

    2012-01-01

    High dose methotrexate (HD-MTX), used in the treatment of children with acute lymphoblastic leukemia (ALL), is moderately emetogenic. First generation 5-HT(3) receptor antagonists are effective prophylactic agents but require multiple administrations. Palonosetron has a half life of 36-42 hours...... of palonosetron (5 µg/kg) for the prevention of chemotherapy-induced nausea and vomiting in children 18 years of age with ALL treated with HD-MTX, 5 g/m(2)....

  15. HIGH-DOSE RATE BRACHYTHERAPY IN CARCINOMA CERVIX STAGE IIIB

    Directory of Open Access Journals (Sweden)

    Sathya Maruthavanan

    2016-07-01

    Full Text Available INTRODUCTION Radiotherapy is the standard treatment in locally advanced (IIB-IVA and early inoperable cases. The current standard of practice with curable intent is concurrent chemoradiation in which intracavitary brachytherapy is an integral component of radiotherapy. This study aims at assessing the efficacy of HDR ICBT (High-dose rate intracavitary brachytherapy in terms local response, normal tissue reactions, and feasibility. METHODS AND MATERIALS A total of 20 patients of stage IIIB cancer of the uterine cervix were enrolled in the study and were planned to receive concurrent chemotherapy weekly along with EBRT (external beam radiotherapy to a dose of 50 Gy/25 Fr. Suitability for ICBT was assessed at 40 Gy/20 Fr. 6/20 patients were suitable at 40 Gy and received HDR ICBT with a dose of 5.5 Gy to point A in 4 sessions (5.5 Gy/4 Fr. The remaining 14/20 patients completed 50 Gy and received HDR ICBT with a dose of 6 Gy to point A in 3 sessions (6 Gy/3 Fr. RESULTS A total of 66 intracavitary applications were done and only one application required dose modification due to high bladder dose, the pelvic control rate was 85% (17/20. 10% (2/20 had stable disease and 5% (1/20 had progressive disease at one year of follow up. When toxicity was considered only 15% developed grade I and grade II rectal complications. Patient compliance and acceptability was 100%. Patients were very comfortable with the short treatment time as compared with patients on LDR ICBT (low-dose rate intracavitary brachytherapy treatment interviewed during the same period. CONCLUSION This study proves that HDR brachytherapy is efficacious and feasible in carcinoma of cervix stage IIIB. It also proves that good dose distribution can be achieved with HDR intracavitary facility by the use of dose optimization. The short treatment time in HDR ICBT makes it possible to maintain this optimised dose distribution throughout the treatment providing a gain in the therapeutic ratio and

  16. High dose rate brachytherapy for the treatment of soft tissue sarcoma of the extremity

    International Nuclear Information System (INIS)

    Speight, J.L.; Streeter, O.E.; Chawla, S.; Menendez, L.E.

    1996-01-01

    Purpose: we examined the role of preoperative neoadjuvant chemoradiation and adjuvant high-dose rate brachytherapy on the management of prognostically unfavorable soft tissue sarcomas of the extremities. Our goal was to examine the effect of high dose rate interstitial brachytherapy (HDR IBT) on reducing the risk of local recurrence following limb-sparing resection, as well as shortening treatment duration. Materials and methods: eleven patients, ranging in age from 31 to 73 years old, with soft tissue sarcoma of the extremity were treated at USC/Norris Comprehensive Cancer Center during 1994 and 1995. All patients had biopsy proven soft tissue sarcoma, and all were suitable candidates for limb-sparing surgery. All lesions were greater than 5cm in size and were primarily high grade. Tumor histologies included malignant fibrous histiocytoma (45%), liposarcoma (18%) and leiomyosarcoma, synovial cell sarcoma and spindle cell sarcoma (36%). Sites of tumor origin were the lower extremity (55%), upper extremity (18%) and buttock (9%), 1 patient (9%) had lesions in both the upper and lower extremity. Patients received HDR IBT following combined chemotherapy and external beam irradiation (EBRT) and en bloc resection of the sarcoma. Neoadjuvant chemotherapy consisted of three to four cycles of either Ifosfamide/Mesna with or without Adriamycin, or Mesna, Adriamycin, Ifosfamide and Dacarbazine. One patient received Cis-platin in addition to Ifos/Adr. A minimum of two cycles of chemotherapy were administered prior to EBRT. Additional cycles of chemotherapy were completed concurrently with EBRT but prior to HDR IBT. Preoperative EBRT doses ranging from 40 to 59.4 Gy were given in daily fractions of 180 to 200cGy. Following en bloc resection, HDR IBT was administered using the Omnitron tm 2000 remote afterloading system. Doses ranging from 13 to 30 Gy were delivered to the surgical tumor bed at depths of 0.5mm to 0.75mm from the radioactive source. Results: median follow-up was

  17. Accelerated Irradiations for High Dose Microstructures in Fast Reactor Alloys

    Energy Technology Data Exchange (ETDEWEB)

    Jiao, Zhijie [Univ. of Michigan, Ann Arbor, MI (United States)

    2017-03-31

    The objective of this project is to determine the extent to which high dose rate, self-ion irradiation can be used as an accelerated irradiation tool to understand microstructure evolution at high doses and temperatures relevant to advanced fast reactors. We will accomplish the goal by evaluating phase stability and swelling of F-M alloys relevant to SFR systems at very high dose by combining experiment and modeling in an effort to obtain a quantitative description of the processes at high and low damage rates.

  18. Effective chemotherapy of acute myelocytic leukemia occurring after alkylating agent or radiation therapy for prior malignancy

    International Nuclear Information System (INIS)

    Vaughan, W.P.; Karp, J.E.; Burke, P.J.

    1983-01-01

    Eleven consecutive patients with acute myelocytic leukemia occurring as a second malignancy were treated with high-dose, timed, sequential chemotherapy. Eight of the patients were felt to have ''secondary'' acute leukemia because they had received an alkylating agent or radiation therapy. The other three patients were considered controls. Despite a median age of 65, four of the eight secondary leukemia patients achieved complete remission with this regimen. One of the three control patients also achieved complete remission. This remission rate and duration are comparable to what was achieved with this treatment of ''primary'' acute myelocytic leukemia during the same period of time. These results suggest that patients with leukemia occurring after an alkylating agent or radiation therapy are not at especially high risk if treated aggressively

  19. Relative safety profiles of high dose statin regimens

    Directory of Open Access Journals (Sweden)

    Carlos Escobar

    2008-06-01

    Full Text Available Carlos Escobar, Rocio Echarri, Vivencio BarriosDepartment of Cardiology, Hospital Ramón y Cajal, Madrid, SpainAbstract: Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses.Keywords: statins, high doses, tolerability, liver, muscle

  20. Treatment of the prostate cancer with high dose rate brachytherapy

    International Nuclear Information System (INIS)

    Martinez, Alvaro; Torres Silva, Felipe

    2002-01-01

    The prostate cancer treatment in early stages is controversial. The high dose rate brachytherapy has been used like monotherapy or boost with external beam radiotherapy in advanced disease. This paper describes the technique and the advantages over other modalities

  1. High-dose dosimetry using natural silicate minerals

    International Nuclear Information System (INIS)

    Carmo, Lucas S. do; Mendes, Leticia; Watanabe, Shigueo; Rao, Gundu; Lucas, Natasha; Sato, Karina; Barbosa, Renata F.

    2015-01-01

    In the present study, certain natural silicate minerals such as aquamarine (AB), morganite (PB), goshenite (WB), white jadeite (JW), green jadeite (JG), pink tourmaline (PT) and two varieties of jadeite-like quartz, denoted here by JQ1 and JQ2, were investigated using the thermoluminescence technique to evaluate their potential for use as very-high- and high-dose dosimeters. These minerals respond to high doses of γ-rays of up to 1000 kGy and often to very high doses of up to 3000 kGy. The TL response of these minerals may be considered to be satisfactory for applications in high-dose dosimetry. Investigations of electron paramagnetic resonance and optically stimulated luminescence dosimetry are in progress. (author)

  2. High-dose dosimetry using natural silicate minerals

    Energy Technology Data Exchange (ETDEWEB)

    Carmo, Lucas S. do; Mendes, Leticia, E-mail: isatiro@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Watanabe, Shigueo; Rao, Gundu; Lucas, Natasha; Sato, Karina, E-mail: lacifid@if.usp.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Fisica. Departamento de Fisica Nuclear; Barbosa, Renata F., E-mail: profcelta@hotmail.com [Universidade Federal de Sao Paulo (UNIFESP), Santos, SP (Brazil). Departamento de Ciencias do Mar

    2015-07-01

    In the present study, certain natural silicate minerals such as aquamarine (AB), morganite (PB), goshenite (WB), white jadeite (JW), green jadeite (JG), pink tourmaline (PT) and two varieties of jadeite-like quartz, denoted here by JQ1 and JQ2, were investigated using the thermoluminescence technique to evaluate their potential for use as very-high- and high-dose dosimeters. These minerals respond to high doses of γ-rays of up to 1000 kGy and often to very high doses of up to 3000 kGy. The TL response of these minerals may be considered to be satisfactory for applications in high-dose dosimetry. Investigations of electron paramagnetic resonance and optically stimulated luminescence dosimetry are in progress. (author)

  3. BRCA1-like profile predicts benefit of tandem high dose epirubicin-cyclophospamide-thiotepa in high risk breast cancer patients randomized in the WSG-AM01 trial

    NARCIS (Netherlands)

    Schouten, Philip C.; Gluz, Oleg; Harbeck, Nadia; Mohrmann, Svjetlana; Diallo-Danebrock, Raihana; Pelz, Enrico; Kruizinga, Janneke; Velds, Arno; Nieuwland, Marja; Kerkhoven, Ron M.; Liedtke, Cornelia; Frick, Markus; Kates, Ronald; Linn, Sabine C.; Nitz, Ulrike; Marme, Frederik

    2016-01-01

    BRCA1 is an important protein in the repair of DNA double strand breaks (DSBs), which are induced by alkylating chemotherapy. A BRCA1-like DNA copy number signature derived from tumors with a BRCA1 mutation is indicative for impaired BRCA1 function and associated with good outcome after high dose

  4. Prospective Phase I-II Trial of Helical Tomotherapy With or Without Chemotherapy for Postoperative Cervical Cancer Patients

    International Nuclear Information System (INIS)

    Schwarz, Julie K.; Wahab, Sasa; Grigsby, Perry W.

    2011-01-01

    Purpose: To investigate, in a prospective trial, the acute and chronic toxicity of patients with cervical cancer treated with surgery and postoperative intensity-modulated radiotherapy (RT) delivered using helical tomotherapy, with or without the administration of concurrent chemotherapy. Patients and Methods: A total of 24 evaluable patients entered the study between March 2006 and August 2009. The indications for postoperative RT were tumor size, lymphovascular space invasion, and the depth of cervical stromal invasion in 15 patients; 9 patients underwent postoperative RT because of surgically positive lymph nodes. All patients underwent pelvic RT delivered with helical tomotherapy and intracavitary high-dose-rate brachytherapy. Treatment consisted of concurrent weekly platinum in 17, sequential carboplatin/Taxol in 1, and RT alone in 6. The patients were monitored for acute and chronic toxicity using the Common Toxicity Criteria, version 3.0. Results: The median follow-up was 24 months (range, 4–49). At the last follow-up visit, 23 patients were alive and disease free. Of the 24 patients, 12 (50%) experienced acute Grade 3 gastrointestinal toxicity (anorexia in 5, diarrhea in 4, and nausea in 3). One patient developed acute Grade 4 genitourinary toxicity (vesicovaginal fistula). For patients treated with concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 71% and 24%, respectively. For patients treated without concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 29% and 14%, respectively. Two long-term toxicities occurred (vesicovaginal fistula at 25 months and small bowel obstruction at 30 months). The overall and progression-free survival rate at 3 years for all patients was 100% and 89%, respectively. Conclusion: The results of our study have shown that postoperative external RT for cervical cancer delivered with helical tomotherapy and high-dose-rate brachytherapy and with or without

  5. Prospective Phase I-II Trial of Helical Tomotherapy With or Without Chemotherapy for Postoperative Cervical Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Schwarz, Julie K., E-mail: jschwarz@radonc.wustl.edu [Department of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Department of Cell Biology and Physiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Wahab, Sasa [Cobb Center for Radiation Oncology Center, Austell, GA (United States); Grigsby, Perry W. [Department of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Department of Obstetrics and Gynecology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States)

    2011-12-01

    Purpose: To investigate, in a prospective trial, the acute and chronic toxicity of patients with cervical cancer treated with surgery and postoperative intensity-modulated radiotherapy (RT) delivered using helical tomotherapy, with or without the administration of concurrent chemotherapy. Patients and Methods: A total of 24 evaluable patients entered the study between March 2006 and August 2009. The indications for postoperative RT were tumor size, lymphovascular space invasion, and the depth of cervical stromal invasion in 15 patients; 9 patients underwent postoperative RT because of surgically positive lymph nodes. All patients underwent pelvic RT delivered with helical tomotherapy and intracavitary high-dose-rate brachytherapy. Treatment consisted of concurrent weekly platinum in 17, sequential carboplatin/Taxol in 1, and RT alone in 6. The patients were monitored for acute and chronic toxicity using the Common Toxicity Criteria, version 3.0. Results: The median follow-up was 24 months (range, 4-49). At the last follow-up visit, 23 patients were alive and disease free. Of the 24 patients, 12 (50%) experienced acute Grade 3 gastrointestinal toxicity (anorexia in 5, diarrhea in 4, and nausea in 3). One patient developed acute Grade 4 genitourinary toxicity (vesicovaginal fistula). For patients treated with concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 71% and 24%, respectively. For patients treated without concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 29% and 14%, respectively. Two long-term toxicities occurred (vesicovaginal fistula at 25 months and small bowel obstruction at 30 months). The overall and progression-free survival rate at 3 years for all patients was 100% and 89%, respectively. Conclusion: The results of our study have shown that postoperative external RT for cervical cancer delivered with helical tomotherapy and high-dose-rate brachytherapy and with or without

  6. Implementation of high-dose chemical dosimetry for industrial facilities

    International Nuclear Information System (INIS)

    Conceicao, Cirilo Cezar Sant'Anna da

    2006-01-01

    The purpose of this work is the implementation of methodology for high dose measurements using chemical dosimeters in liquid phase, traceable to the international metrology system, and make available in the country, the standard of high-dose to industrial irradiation facilities and research irradiators, trough the quality program with comparative measurements and direct use of the standard dosimeters in routine. The use of these low cost dosimetry systems in industrial irradiation facilities, assists to the certification requirements and it can reduce the costs with dosimetry for approximately 20% of the total dosimetry costs, using these systems in routine measurements and validation process, largely substituting the imported PMMA dosimeters, among others. (author)

  7. Statistical behavior of high doses in medical radiodiagnosis

    International Nuclear Information System (INIS)

    Barboza, Adriana Elisa

    2014-01-01

    This work has as main purpose statistically estimating occupational exposure in medical diagnostic radiology in cases of high doses recorded in 2011 at national level. For statistical survey of this study, doses of 372 IOE's diagnostic radiology in different Brazilian states were evaluated. Data were extracted from the work of monograph (Research Methodology Of High Doses In Medical Radiodiagnostic) that contains the database's information Sector Management doses of IRD/CNEN-RJ, Brazil. The identification of these states allows the Sanitary Surveillance (VISA) responsible, becomes aware of events and work with programs to reduce these events. (author)

  8. Study of teflon pads as high doses dosemeters

    International Nuclear Information System (INIS)

    Teixeira, Maria Ines; Caldas, Linda V.E.

    2013-01-01

    The aim of this work is to study the Teflon, which is used as a binder in the manufacture of dosimetric tablets, for the feasibility of this material as high dose dosemeter. In this paper we used the technique of thermally stimulated luminescence (OSL) to characterize the dosimetric properties of Teflon. Teflon samples were exposed to different doses of radiation, using a source of gamma radiation ( 60 Co). It was obtained dose-response curve between 100 Gy to 50 kGy and reproducibility of OSL response. The preliminary results show that Teflon is a useful material to high dose dosimetry

  9. Adjuvant chemotherapy for osteosarcoma.

    Science.gov (United States)

    Eilber, F R; Rosen, G

    1989-08-01

    From this review of chemotherapy trials, several observations can be made. Osteosarcoma is a complex disease involving multiple histologies, each with a different prognosis. Prognostic factors that have been shown to be important include anatomic location of the primary tumor, stage at presentation (patients with metastatic or local recurrent disease fair far worse than those with primary disease), age at onset (children fair worse than the teenager with osteosarcoma), and location within the extremity (patients with more distal tumors fairing better than patients with more proximal tumors). There is convincing evidence for the efficacy of chemotherapeutic agents such as methotrexate in high doses (at least 8 g/m2 for adults, 12 g/m2 for children), Adriamycin, and cisplatin. The combination of Adriamycin and cisplatin appears to be more beneficial relative to either one of these agents alone. The efficacy of the combination of BCD as a triple-drug regimen, although useful in several different trials, has not been convincingly shown. Finally, from several of the recent randomized trials, it appears, that chemotherapeutic regimens containing an Adriamycin and cisplatin combination appear to be superior to those that do not include this combination. However, these observations are made from a historical perspective and have not been conclusively proven by randomized prospective investigations. The observations concerning the natural history of the disease and the activity of various chemotherapeutic agents suggest certain clinical practice algorithms. Essential staging procedures would include a bone scan looking for multifocal or metastatic disease, and CT scans of the chest looking for metastases to the lung. From all studies, it is apparent that surgery is mandatory for the primary tumor and should be an integral portion of all treatment methods. Chemotherapy should be considered for all patients with osteosarcoma, and the essential drugs in the regimen appear at

  10. Sequential Use of Second-Generation Tyrosine Kinase Inhibitor Treatment and Intensive Chemotherapy Induced Long-Term Complete Molecular Response in Imatinib-Resistant CML Patient Presenting as a Myeloid Blast Crisis

    Directory of Open Access Journals (Sweden)

    Masaaki Tsuji

    2017-01-01

    Full Text Available Myeloid blast crisis of chronic myeloid leukemia (CML-MBC is rarely seen at presentation and has a poor prognosis. There is no standard therapy for CML-MBC. It is often difficult to distinguish CML-MBC from acute myeloid leukemia expressing the Philadelphia chromosome (Ph+ AML. We present a case in which CML-MBC was seen at the initial presentation in a 75-year-old male. He was treated with conventional AML-directed chemotherapy followed by imatinib mesylate monotherapy, which failed to induce response. However, he achieved long-term complete molecular response after combination therapy involving dasatinib, a second-generation tyrosine kinase inhibitor, and conventional chemotherapy.

  11. CD34-positive cells as stem cell support after high dose therapy

    International Nuclear Information System (INIS)

    Kvalheim, G.; Pharo, A.; Holte, H.

    1996-01-01

    Six patients, five with breast cancer and one with non-Hodgkin's lymphoma, were mobilized by chemotherapy and G-CSF. CD34-positive cells were isolated by means of immunomagnetic beads and Isolex 300 Cell Separator. Mean purity of isolated CD34-positive cells was 97% and mean yield was 54%. Three patients were treated with high dose therapy followed by reinfusion of CD34-positive cells as stem cell support. Recovery of neutrophils occurred at day 8, 11 and 13 and of platelets at day 9, 14 and 32. It is concluded that immunomagnetic isolated CD34-positive cells give high purity and yield. Although use of CD34-positive cells reduces the content of contaminating tumours cells in the graft, breast cancer cells were still detectable in two out of five CD34-positive cell products. 20 refs., 2 figs., 1 tab

  12. Interstitial high-dose rate brachytherapy as boost for anal canal cancer

    International Nuclear Information System (INIS)

    Falk, Alexander Tuan; Claren, Audrey; Benezery, Karen; François, Eric; Gautier, Mathieu; Gerard, Jean-Pierre; Hannoun-Levi, Jean-Michel

    2014-01-01

    To assess clinical outcomes of patients treated with a high-dose rate brachytherapy boost for anal canal cancer (ACC). From August 2005 to February 2013, 28 patients presenting an ACC treated by split-course external beam radiotherapy (EBRT) and HDR brachytherapy with or without chemotherapy in a French regional cancer center in Nice were retrospectively analyzed. Median age was 60.6 years [34 – 83], 25 patients presented a squamous cell carcinoma and 3 an adenocarcinoma; 21 received chemotherapy. Median dose of EBRT was 45 Gy [43.2 – 52]. Median dose of HDR brachytherapy was 12 Gy [10 - 15] with a median duration of 2 days. Median overall treatment time was 63 days and median delay between EBRT and brachytherapy was 20 days. Two-year local relapse free, metastatic free, disease free and overall survivals were 83%, 81.9%, 71.8% and 87.7% respectively. Acute toxicities were frequent but not severe with mostly grade 1 toxicities: 37% of genito-urinary, 40.7% of gastro-intestinal and 3.7% of cutaneous toxicities. Late toxicities were mainly G1 (43.1%) and G2 (22%). Two-year colostomy-free survival was 75.1%, one patient had a definitive sphincter amputation. High-dose rate brachytherapy for anal canal carcinoma as boost represents a feasible technique compared to low or pulsed-dose rate brachytherapy. This technique remains an excellent approach to precisely boost the tumor in reducing the overall treatment time

  13. Low- and high-dose laser irradiation effects on cell migration and destruction

    Science.gov (United States)

    Layton, Elivia; Gallagher, Kyra A.; Zukerman, Sara; Stevens, Brianna; Zhou, Feifan; Liu, Hong; Chen, Wei R.

    2018-02-01

    Metastases are the cause of more than 90 percent of cancer-related deaths. Current treatment methods, including chemotherapy, radiation, and surgery, fail to target the metastases effectively. One potential treatment for metastatic cancer is laser immunotherapy (LIT). LIT combines the use of a photothermal laser with an immunoadjuvant, Glycated Chitosan (GC). GC combined with single-walled carbon nanotubes (SWNTs) has proven to be a viable alternative to traditional cancer treatment methods, when under irradiation of laser with appropriate wavelength. In this study, the effects of low dose and high dose laser irradiation on metastatic pancreatic cancer cell migration were observed. It was found that low dose irradiation increased the migration rate, but the high dose irradiation significantly decreased the migration rate of the cancer cells. When using LIT, the goal is to kill tumor cells and to prompt the correct immune response. If the tumor were irradiated with a low dose, it would promote metastasis. If the dose of irradiation were too high, it would destroy the entire tumor and the immune response would not recognize the tumor. Therefore, the laser dose plays an important role in LIT, particularly when using SWNT as light absorbing agent. Our results from this study will delineate the optimal laser irradiation dose for destroying tumor cells and at the same time preserve and release tumor antigens as a precursor of antitumor immune response.

  14. Definitive intraoperative very high-dose radiotherapy for localized osteosarcoma in the extremities

    International Nuclear Information System (INIS)

    Oya, Natsuo; Kokubo, Masaki; Mizowaki, Takashi; Shibamoto, Yuta; Nagata, Yasushi; Sasai, Keisuke; Nishimura, Yasumasa; Tsuboyama, Tadao; Toguchida, Junya; Nakamura, Takashi; Hiraoka, Masahiro

    2001-01-01

    Purpose: To evaluate the outcome and adverse effects in patients with osteosarcoma treated with very high-dose definitive intraoperative radiotherapy (IORT), with the intention of saving the affected limb. Methods and Materials: Thirty-nine patients with osteosarcoma in their extremities were treated with definitive IORT. The irradiation field included the tumor plus an adequate wide margin and excluded the major vessels and nerves. Forty-five to 80 Gy of electrons or X-rays were delivered. The median follow-up of the surviving patients was 124 months. Results: The cause-specific and relapse-free 5-year survival rate was 50% and 43%, respectively. Distant metastasis developed in 23 patients; 19 died and 4 were alive for >10 years. Nine local recurrences were found 4-29 months after IORT in the affected limb. No radiation-induced skin reaction or nerve palsy was observed in the patients treated with X-rays. Experiments using phantoms also confirmed that the scatter dose was below the toxic level in the IORT setting with X-rays. Conclusions: Very high-dose definitive IORT combined with preventive nailing and chemotherapy appeared to be a promising quality-of-life-oriented alternative to treating patients with osteosarcomas in the extremities, although the problem of recurrences from the surrounding unirradiated soft tissue remains to be solved

  15. Oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Aisa, Yoshinobu; Mori, Takehiko; Kudo, Masumi; Yashima, Tomoko; Kondo, Sakiko; Yokoyama, Akihiro; Ikeda, Yasuo; Okamoto, Shinichiro

    2005-04-01

    The purpose of this study was to evaluate the efficacy of oral cryotherapy to prevent high-dose melphalan-induced stomatitis. Eighteen consecutive recipients of allogeneic hematopoietic stem cell transplant conditioned with high-dose melphalan (140 mg/m2) in combination with fludarabine alone or with fludarabine and additional chemotherapy or radiation were enrolled. The severity of stomatitis was graded according to the National Cancer Institute Common Toxicity Criteria. Patients were kept on oral cryotherapy using ice chips and ice-cold water shortly before, during, and for additional 90 min after completion of melphalan administration. Only two of 18 patients (11.1%) developed grade 2 or 3 stomatitis while six of seven patients in the historical control developed it (85.7%; P=0.001). These results suggested that oral cryotherapy could effectively prevent stomatitis caused by high-dose melphalan, and we recommend that it should be incorporated into the conditioning regimen with high-dose melphalan.

  16. Primary treatment of acromegaly with high-dose lanreotide: a case series

    Directory of Open Access Journals (Sweden)

    Cordes Uwe

    2010-03-01

    Full Text Available Abstract Introduction The first-line treatment for acromegaly is transsphenoidal surgery. In approximately 50% of patients, however, a cure is not possible with surgery and alternatives are needed. Somatostatin analog therapy is the recommended first-line treatment in patients with such cases. Here we provide the first report of a high-dose lanreotide primary therapy in patients with acromegaly. Case presentation Six patients who were not suitable for surgery were given 60 mg of lanreotide (Autogel® every four weeks. All patients were German nationals and Caucasian. When the response of our patients was unsatisfactory, the dose was increased sequentially to 90 mg every four weeks, 120 mg every four weeks, 120 mg every three weeks and 180 mg every three weeks. Treatment duration was 12 to 24 months. In all cases, the lanreotide dose was 120 mg every 4 weeks or higher. In five of our patients, growth hormone (GH levels were successfully reduced (in three patients GH Tumor shrinkage or degeneration was observed in the five responding patients. No drug-related adverse events were noted. Conclusions These results suggest that lanreotide at high doses of 120 mg every four weeks or more is an effective first-line therapy for patients with acromegaly that surgery alone cannot treat.

  17. Use of glasses as radiation detectors for high doses

    International Nuclear Information System (INIS)

    Caldas, L.

    1989-08-01

    Glass samples were tested in relation to the possibility of use in high dose dosimetry in medical and industrial areas. The main characteristics were determined: detection threshold, reproducibility, response to gamma radiation of 137 Cs and 6 Co and thermal decay at ambient temperature, with the use of optical absorption and thermoluminesce techniques. (author) [pt

  18. Oval pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

    Hoogendijk, JE; Wokke, JHJ; de Visser, M

    To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Sis patients responded. Side effects

  19. Oral pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

    van der Meulen, M. F.; Hoogendijk, J. E.; Wokke, J. H.; de Visser, M.

    2000-01-01

    To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Six patients responded. Side effects

  20. Safety and tolerability of high doses of glucocorticoides

    Directory of Open Access Journals (Sweden)

    Rakić Branislava D.

    2016-01-01

    Full Text Available Introduction: Treatment of acute lymphoblastic leukemia includes the use of high doses of glucocorticoides (prednisone and dexamethasone, which significantly increase the success of therapy due to lymphocytolitic effect. The aim: The aim of the study was to determine tolerability of high doses of prednisone and dexamethasone in children with acute lymphoblastic leukemia and the structure and the intensity of adverse effects, occurred after application of these medicines. Subjects and methods: In a prospective study, we analyzed adverse effects of high doses of glucocorticoides in children suffering acute lymphoblastic leukemia treated in the Institute for Child and Youth Health Care of Vojvodina, since December 2010. until October 2014, were analyzed. This study included 18 patients, aged from 2 to 15 years. Results: Hyperglycemia appeared in 89% of patients treated with prednisone and in 61% of patients treated with dexamethasone. In order to control the high blood glucose level (above 10 mmol /L, in 11% of patients insulin was used. Hypertension appeared in 28% patients treated with prednisone and dexamethasone. Antihypertensives were needed for regulation in 17% patients. Hypopotassemia and hypocalcaemia were significantly more expressed after the use of prednisone in comparison to dexamethasone. In 11% of patients, the treatment with dexamethasone caused depressive behavior, followed by agitation. Conclusion: Adverse effects of dexamethasone and prednisone, administered in high doses in children with ALL were known, expected and reversible. Adverse reactions usually disappeared spontaneously or after short-term symptomatic therapy.

  1. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

    NARCIS (Netherlands)

    P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth)

    2005-01-01

    textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

  2. Concurrent radiotherapy and chemotherapy

    International Nuclear Information System (INIS)

    Fu, K.K.

    1985-01-01

    The principal objective of combining chemotherapy with radiotherapy (XRT) for the treatment of advanced head and neck cancer is to improve the therapeutic ratio through the enhancement of local control and reduction of distant metastases without excessively enhancing normal tissue effects. Improved tumour control can result from sole additivity of either therapy or direct interactions between drug and radiation leading to increased tumour cell kill. Chemotherapy may sensitize the cells to radiation, interfere with repair of sublethal or potentially lethal radiation damage, induce cell synchrony, and reduce tumour mass leading to reoxygenation and decreased fraction of resistant hypoxic cells. Radiation may improve drug accessibility to tumour cells and reduce tumour volume leading to increased cell proliferation and chemosensitivity. If the enhanced effects of combined therapy are purely additive, then the two modalities can be administered either sequentially or concurrently with the same results. However, if the enhanced effects result from the direct interaction between drug and radiation, it is necessary that the two modalities be administered concurrently and in close temporal proximity. This review summarizes the results of clinical studies in which chemotherapy was administered concurrently during the course of radiotherapy for patients with previously untreated advanced squamous cell carcinoma in the head and neck

  3. The 21-gene Recurrence Score® assay predicts distant recurrence in lymph node-positive, hormone receptor-positive, breast cancer patients treated with adjuvant sequential epirubicin- and docetaxel-based or epirubicin-based chemotherapy (PACS-01 trial).

    Science.gov (United States)

    Penault-Llorca, Frédérique; Filleron, Thomas; Asselain, Bernard; Baehner, Frederick L; Fumoleau, Pierre; Lacroix-Triki, Magali; Anderson, Joseph M; Yoshizawa, Carl; Cherbavaz, Diana B; Shak, Steven; Roca, Lise; Sagan, Christine; Lemonnier, Jérôme; Martin, Anne-Laure; Roché, Henri

    2018-05-04

    The 21-gene Recurrence Score (RS) result predicts outcome and chemotherapy benefit in node-negative and node-positive (N+), estrogen receptor-positive (ER+) patients treated with endocrine therapy. The purpose of this study was to evaluate the prognostic impact of RS results in N+, hormone receptor-positive (HR+) patients treated with adjuvant chemotherapy (6 cycles of FEC100 vs. 3 cycles of FEC100 followed by 3 cycles of docetaxel 100 mg/m 2 ) plus endocrine therapy (ET) in the PACS-01 trial (J Clin Oncol 2006;24:5664-5671). The current study included 530 HR+/N+ patients from the PACS-01 parent trial for whom specimens were available. The primary objective was to evaluate the relationship between the RS result and distant recurrence (DR). There were 209 (39.4%) patients with low RS (< 18), 159 (30%) with intermediate RS (18-30) and 162 (30.6%) with high RS (≥ 31). The continuous RS result was associated with DR (hazard ratio = 4.14; 95% confidence interval: 2.67-6.43; p <  0.001), adjusting for treatment. In multivariable analysis, the RS result remained a significant predictor of DR (p <  0.001) after adjustment for number of positive nodes, tumor size, tumor grade, Ki-67 (immunohistochemical status), and chemotherapy regimen. There was no statistically significant interaction between RS result and treatment in predicting DR (p = 0.79). After adjustment for clinical covariates, the 21-gene RS result is a significant prognostic factor in N+/HR+ patients receiving adjuvant chemoendocrine therapy. Not applicable.

  4. Treatment of locally advanced breast carcinoma with high-dose external beam supervoltage radiotherapy

    International Nuclear Information System (INIS)

    Brufman, G.; Weshler, Z.; Prosnitz, L.R.; Fuks, Z.

    1981-01-01

    Between 1960 and 1978, 87 patients with locally advanced Tsub(3-4)Nsub(0-3)M 0 carcinoma of the breast were treated with 5,000 to 8,000 rad of external beam supervoltage radiotherapy. Initial clinical eradication of the tumour was observed in 76 of 87 cases (87%), but the actuarial probability of local control at 5 yr was only 53%. Furthermore, the actuarial probability of disease-free survival was 25% at 5 yr and 13% at 10 yr. Most of the patients eventually succumbed to metastatic breast carcinoma and the actuarial survival at 5 yr was 43% and at 10 yr, 16%. The addition of adjuvant low-dose chemotherapy, given to 13 patients, did not affect the rates of local control, survival or disease-free survival. The most common long-term complication was extensive and deforming radiation-induced fibrosis of the treated breast. The actuarial probability of 10-yr survival without a local recurrence and without severe fibrosis of the treated breast was only 17.5%. The role of adjuvant high-dose chemotherapy in the treatment of locally advanced breast carcinoma and the possible use of improved radiotherapy techniques to achieve a more effective long-term local control and a more desirable cosmetic end result are discussed. (author)

  5. Hypofractionated High-Dose Irradiation with Positron Emission Tomography Data for the Treatment of Glioblastoma Multiforme

    Directory of Open Access Journals (Sweden)

    Kazuhiro Miwa

    2014-01-01

    Full Text Available This research paper presents clinical outcomes of hypofractionated high-dose irradiation by intensity-modulated radiation therapy (Hypo-IMRT with 11C-methionine positron emission tomography (MET-PET data for the treatment of glioblastoma multiforme (GBM. A total of 45 patients with GBM were treated with Hypo-IMRT after surgery. Gross tumor volume (GTV was defined as the area of enhanced lesion on MRI, including MET-PET avid region; clinical target volume (CTV was the area with 5 mm margin surrounding the GTV; planning target volume (PTV was the area with 15 mm margin surrounding the CTV, including MET-PET moderate region. Hypo-IMRT was performed in 8 fractions; planning the dose for GTV was escalated to 68 Gy and that for CTV was escalated to 56 Gy, while keeping the dose delivered to the PTV at 40 Gy. Concomitant and adjuvant TMZ chemotherapy was administered. At a median follow-up of 18.7 months, median overall survival (OS was 20.0 months, and median progression-free survival was 13.0 months. The 1- and 2-year OS rates were 71.2% and 26.3%, respectively. Adjuvant TMZ chemotherapy was significantly predictive of OS on multivariate analysis. Late toxicity included 7 cases of Grade 3-4 radiation necrosis. Hypo-IMRT with MET-PET data appeared to result in favorable survival outcomes for patients with GBM.

  6. Practice of superselective intraarterial high-dose cisplatin chemoradiotherapy in the oral cavity

    International Nuclear Information System (INIS)

    Yoshida, Tomoyuki; Nakamura, Kazuhiro; Tsukahara, Kiyoaki; Inagaki, Taro; Ito, Hiroyuki; Shimizu, Akira; Takata, Daisuke; Okamoto, Isaku; Kondo, Takahito

    2011-01-01

    Superselective intraarterial infusion enables high-dose chemotherapeutic agents to be administered via tumor feeding vessels to neutralize and limit the adverse cisplatin effects acceptable. Between 1998 and 2008, we evaluated the efficacy of first-line therapy and adverse events in 30 subjects with oral squamous cell cancer undergoing simultaneous superselective intra arterial high-dose chemotherapy and radiotherapy. The 30 subjects- 23 men and 7 women aged 40 to 72- consisted of 3 T2, 12 T3, and 15 T4. Four patients had N0, 8 N1, 7 N2b, 8 N2c, and 3 N3 disease. Two were in CS II, 6 III, 17 IVa, and 5 IVb (III>93%, IV: 73%). Superselective intra arterial chemotherapy delivered through the femoral artery used the Seldinger technique. A single cisplatin dose of 100-550 mg/m 2 (mean 440 mg/m 2 ). Five minutes after intra arterial infusion, sodium thiosulphate (9 g/m 2 ) was administered via a peripheral cutaneous vein in the contralateral forearm. Concurrent radiotherapy started on Day 2 at 2 Gy per session for a total of 60 Gy. Two to 3 weeks later, 15 under went the second course of superselective intra arterial chemotherapy after tumor feeding vessels were visualized angiographically. Four (13.3%) subjects with Grade 3 or greater myelosuppression required granulocyte-colony stimulating factor (G-CSF). Grade 3 or greater mucositis was observed in 57% and Grade 4 mucositis occurred in 5 (16.7%). All adverse effects were reversible and no serious adverse events were prolonged. Among those responding to first-line therapy, 24 of the 30 (80%) achieved complete response (CR) and 6 (20%) partial response (PR), but no stable disease (SD) or no change (NC). Overall response was 100%. Histopathologically, 2 of 9 undergoing postchemoradiotherapy had no tumors. Clinical and pathological CR was 86.7%. Adverse events associated with this therapy associated events were considered relatively mild and within allowable limits. (author)

  7. Metronomic chemotherapy.

    Science.gov (United States)

    Mutsaers, Anthony J

    2009-08-01

    Chemotherapy drugs are usually administered at doses that are high enough to result in an obligatory break period to allow for the observation of potential side effects and institution of supportive care, if required. In recent years, efforts to administer chemotherapy on a more continuous basis, with a much shorter break period, or none at all, have received increased interest, and the practice has come to be known as metronomic chemotherapy. The basis for success with this currently investigational approach may be rooted in continuous drug exposure to susceptible cancer cells, inhibition of tumor blood vessel growth-a process known as tumor angiogenesis, and/or alterations in tumor immunology. Increased benefit also appears to occur when metronomic chemotherapy is used in combination with newer, targeted antiangiogenic agents, and therefore represents a promising approach to combination therapy, particularly as targeted oncology drugs make their way into veterinary oncology applications. There is still much to be learned in this field, especially with regard to optimization of the proper drugs, dose, schedule, and tumor applications. However, the low cost, ease of administration, and acceptable toxicity profiles potentially associated with this therapeutic strategy make metronomic chemotherapy protocols attractive and suitable to veterinary applications. Preliminary clinical trial results have now been reported in both human and veterinary medicine, including adjuvant treatment of canine splenic hemangiosarcoma and incompletely resected soft tissue sarcoma, and, further, more powerful studies are currently ongoing.

  8. High-dose secondary calibration laboratory accreditation program

    Energy Technology Data Exchange (ETDEWEB)

    Humphreys, J.C. [National Institute of Standards and Technology, Gaithersburg, MD (United States)

    1993-12-31

    There is a need for high-dose secondary calibration laboratories to serve the multi-billion dollar radiation processing industry. This need is driven by the desires of industry for less costly calibrations and faster calibration-cycle response time. Services needed include calibration irradiations of routine processing dosimeters and the supply of reference standard transfer dosimeters for irradiation in the production processing facility. In order to provide measurement quality assurance and to demonstrate consistency with national standards, the high-dose secondary laboratories would be accredited by means of an expansion of an existing National Voluntary Laboratory Accreditation Program. A laboratory performance criteria document is under development to implement the new program.

  9. High-dose secondary calibration laboratory accreditation program

    International Nuclear Information System (INIS)

    Humphreys, J.C.

    1993-01-01

    There is a need for high-dose secondary calibration laboratories to serve the multi-billion dollar radiation processing industry. This need is driven by the desires of industry for less costly calibrations and faster calibration-cycle response time. Services needed include calibration irradiations of routine processing dosimeters and the supply of reference standard transfer dosimeters for irradiation in the production processing facility. In order to provide measurement quality assurance and to demonstrate consistency with national standards, the high-dose secondary laboratories would be accredited by means of an expansion of an existing National Voluntary Laboratory Accreditation Program. A laboratory performance criteria document is under development to implement the new program

  10. Anticoagulation and high dose liver radiation. A preliminary report

    International Nuclear Information System (INIS)

    Lightdale, C.J.; Wasser, J.; Coleman, M.; Brower, M.; Tefft, M.; Pasmantier, M.

    1979-01-01

    Two groups of patients were observed for evidence of acute radiation hepatitis during high dose radiation to the liver. The first group of 18 patients with metastatic liver disease received an average of 4,050 rad to the whole liver. Half received anticoagulation with warfarin. One patient on anticoagulation developed evidence of acute radiation hepatitis while 2 patients did so without anticoagulation. Eleven patients with Hodgkin's disease received 4,000 rad to the left lobe of the liver during extended field radiation. Four of these 11 patients were anticoagulated to therapeutic range. Only one of the fully anticoagulated patients showed changes on liver scan consistent with radiation hepatitis whereas three did so without anticoagulation. No serious sequelae from anticoagulation occurred in either group. These preliminary data suggest that anticoagulation may be safely administered with high dose hepatic radiation and that further trials with anticoagulation are warranted

  11. High-dose buprenorphine: perioperative precautions and management strategies.

    Science.gov (United States)

    Roberts, D M; Meyer-Witting, M

    2005-02-01

    Buprenorphine has been in clinical use in anaesthesia for several decades. Recently, the high-dose sublingual formulation (Subutex, Reckitt Benckiser, Slough, U.K.) has been increasingly used as maintenance therapy in opioid dependence, as an alternative to methadone and other pharmacological therapies. Buprenorphine has unique pharmacological properties making it well suited for use as a maintenance therapy in opioid dependence. However, these same properties may cause difficulty in the perioperative management of pain. Buprenorphine is a partial opioid agonist, attenuating the effects of supplemental illicit or therapeutic opioid agonists. As a result of its high receptor affinity, supplemental opioids do not readily displace buprenorphine from the opioid receptor in standard doses. High-dose buprenorphine has an extended duration of action that prolongs both of these effects. The perioperative management of patients stabilized on high-dose buprenorphine and undergoing surgery requires consideration of the likely analgesic requirements. Where possible the buprenorphine should be continued. Pain management should focus on maximizing non-opioid analgesia, local anaesthesia and non-pharmacological techniques. Where pain may not be adequately relieved by these methods, the addition of a full opioid agonist such as fentanyl or morphine at appropriate doses should be considered, accompanied by close monitoring in a high dependency unit. In situations where this regimen is unlikely to be effective, preoperative conversion to morphine or methadone may be an option. Where available, liaison with a hospital-based alcohol and drug service should always be considered.

  12. A novel theory of radiation damage at high doses

    International Nuclear Information System (INIS)

    Seeger, A.; Stuttgart Univ.

    1989-01-01

    Deviations of radiation damage (in the case of metals usually monitored by the residual electrical resistivity) from proportionality with the irradiation dose have so far been analysed almost exclusively in terms of extensions of models originally developed for small doses. The present theory considers the opposite limit i.e. the quasi-saturated state. It is argued that at high doses the Lueck-Sizmann effect may result in a self-organization of clusters of vacancies and self-interstitials, forming a heterogeneous froth. Possible structures of this froth and its effect on the electrical resistivity of metals are discussed. The model is shown to account for the dependence of the ''saturation resistivity'' on the nature of the irradiation as well as for several other hitherto poorly explained observations. Among them are the electrical-resistivity variation induced by high-dose irradiation with heavy ions, the amorphization of certain alloys by high-dose electron irradiation, and the occurrence of ordered arrays of stacking-fault tetrahedra after in-situ irradiations in high-voltage electron microscopes. (author)

  13. Radiophotoluminescence light scope for high-dose dosimetry

    International Nuclear Information System (INIS)

    Sato, Fuminobu; Zushi, Naoki; Sakiyama, Tomoki; Kato, Yushi; Murata, Isao; Shimizu, Kikuo; Yamamoto, Takayoshi; Iida, Toshiyuki

    2015-01-01

    A radiophotoluminescence (RPL) light scope is a remote-sensing technique for measuring in situ the radiation dose in an RPL detector placed at a distance. The RPL light scope is mainly composed of an ultraviolet (UV) pulse laser, telescopic lenses, a photomultiplier tube, and camera modules. In a performance test, some RPL detectors were placed at distances up to 30 m and were illuminated with a pulsed UV laser beam. The photoluminescence responses of the RPL detectors were analyzed using this scope. Their radiation doses were determined from the amplitude of the given component of the photoluminescence responses. The RPL readout could be repeated without fading, and its amplitude exhibited good linearity at a dose ranging from 0.1 to 60 Gy. Furthermore, a two-dimensional distribution of radiation dose was obtained by laser scanning on an RPL detector. It was confirmed that the RPL light scope was a useful remote-sensing tool for high-dose dosimetry. - Highlights: • A radiophotoluminescence (RPL) light scope was developed for high-dose dosimetry. • The RPL light scope has high sensitivity and accuracy in high-dose dosimetry. • Two-dimensional radiation dose distribution was obtained by the RPL light scope.

  14. Precision, high dose radiotherapy: helium ion treatment of uveal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Saunders, W.M.; Char, D.H.; Quivey, J.M.; Castro, J.R.; Chen, G.T.Y.; Collier, J.M.; Cartigny, A.; Blakely, E.A.; Lyman, J.T.; Zink, S.R.

    1985-02-01

    The authors report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a helium ion beam over the tumor volume. The technique localizes the high dose region very tightly around the tumor volume. This allows critical structures, such as the optic disc and the macula, to be excluded from the high dose region as long as they are 3 to 4 mm away from the edge of the tumor. Careful attention to tumor localization, treatment planning, patient immobilization and treatment verification is required. With a mean follow-up of 22 months (3 to 60 months) the authors have had only five patients with a local recurrence, all of whom were salvaged with another treatment. Pretreatment visual acuity has generally been preserved as long as the tumor edge is at least 4 mm away from the macula and optic disc. The only serious complication to date has been an 18% incidence of neovascular glaucoma in the patients treated at our highest dose level. Clinical results and details of the technique are presented to illustrate potential clinical precision in administering high dose radiotherapy with charged particles such as helium ions or protons.

  15. Precision, high dose radiotherapy: helium ion treatment of uveal melanoma

    International Nuclear Information System (INIS)

    Saunders, W.M.; Char, D.H.; Quivey, J.M.

    1985-01-01

    The authors report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a helium ion beam over the tumor volume. The technique localizes the high dose region very tightly around the tumor volume. This allows critical structures, such as the optic disc and the macula, to be excluded from the high dose region as long as they are 3 to 4 mm away from the edge of the tumor. Careful attention to tumor localization, treatment planning, patient immobilization and treatment verification is required. With a mean follow-up of 22 months (3 to 60 months) the authors have had only five patients with a local recurrence, all of whom were salvaged with another treatment. Pretreatment visual acuity has generally been preserved as long as the tumor edge is at least 4 mm away from the macula and optic disc. The only serious complication to date has been an 18% incidence of neovascular glaucoma in the patients treated at our highest dose level. Clinical results and details of the technique are presented to illustrate potential clinical precision in administering high dose radiotherapy with charged particles such as helium ions or protons

  16. High dose Gd-DTPA-BMA (gadodiamide) for diagnostic imaging and therapy monitoring of malignant bone tumors

    International Nuclear Information System (INIS)

    Haeussler, M.D.; Rummeny, E.J.; Raufhake, C.; Blasius, S.; Lindner, N.; Daldrup, H.E.; Reimer, P.; Peters, P.E.

    1996-01-01

    Purpose: To evaluate the efficacy of high-dose Gd-DTPA-BMA (gadodiamide, Omniscan) as a contrast for magnetic resonance imaging of malignant bone tumors and the use of high-dose dynamic studies for predicting the response to preoperative chemotherapy. Materials and methods: Examinations were performed in 22 patients with suspected malignant bone tumor on a 1.5 T system. In 8 cases a follow-up examination was done after preoperative chemotherapy. Static studies included Pd- and T2-weighted spin-echo sequences as well as T1-weighted spin-echo sequences, obtained pre- and post-contrast. Dynamic studies were performed using a FLASH 2D-gradient-echo sequence (TR 40 ms/TE 10 ms, 90 flip angle) every 20 s after intravenous bolus injection of Gd-DTPA-BMA (0.3 mmol/kg body weight). MR images were evaluated qualitatively by visual assessment of conspicuity size, extraosseous delineation and structure of the lesion and quantitatively by measurement of the signal intensities and calculation of the relative increase in signal intensity. Results: Qualitative image analysis showed best demonstration of the lesions on contrast-enhanced T1-weighted images. Comparison of T1-weighted pre- and postcontrast spin-echo sequences revealed significantly better assessment of tumor structure after administration of contrast media. After preoperative chemotherapy, all responders showed a markedly stronger reduction in relative increase in signal intensity in dynamic studies compared to nonresponders. Conclusion: Gd-DTPA-BMA is effective for magnetic resonance imaging of musculoskeletal lesions and improves assessment of the tumor structure. Dynamic studies may help to predict the response to preoperative chemotherapy. (orig.) [de

  17. Improved Metastasis- and Disease-Free Survival With Preoperative Sequential Short-Course Radiation Therapy and FOLFOX Chemotherapy for Rectal Cancer Compared With Neoadjuvant Long-Course Chemoradiotherapy: Results of a Matched Pair Analysis.

    Science.gov (United States)

    Markovina, Stephanie; Youssef, Fady; Roy, Amit; Aggarwal, Sonya; Khwaja, Shariq; DeWees, Todd; Tan, Benjamin; Hunt, Steven; Myerson, Robert J; Chang, Daniel T; Parikh, Parag J; Olsen, Jeffrey R

    2017-10-01

    To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log-rank test was used to compare local control, distant metastasis-free survival, disease-free survival, and overall survival. Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). Patients treated with nTNT had higher T-downstaging and superior distant metastasis-free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a

  18. High dose vitamin K3 infusion in advanced hepatocellular carcinoma.

    Science.gov (United States)

    Sarin, Shiv K; Kumar, Manoj; Garg, Sanjay; Hissar, Syed; Pandey, Chandana; Sharma, Barjesh C

    2006-09-01

    The survival of patients with unresectable advanced hepatocellular carcinoma (HCC) with portal vein thrombosis is dismal. Current therapeutic options have limited efficacy. Vitamin K has been shown to have antitumor effect on HCC cells both in cell lines and patients with advanced HCC. The aim of this study was to assess the clinical efficacy of high dose vitamin K3 in the treatment of advanced HCC with portal vein thrombosis. Forty-two consecutive patients with advanced HCC (Stage C according to BCLC staging system) with portal vein thrombosis were randomized into two groups: (i) high dose vitamin K3 (n = 23); and (ii) placebo (n = 19). The vitamin K3 was administered by i.v. infusion of 50 mg/day with daily increase of dose by 50 mg for 6 days, followed by 20 mg i.m. twice daily for 2 weeks. Of the 23 patients treated with vitamin K, one (4.3%) achieved complete response and three (13%) partial response, for a total of four (17.4%) objective responders overall. The overall mean survival was 8.9 +/- 8.8 months (median: 6; range 1-37 months) in the vitamin K group and 6.8 +/- 5.3 months (median: 5; range 1.5-21 months) in the placebo group (P = 0.552). The mean duration of survival was longer in patients in the vitamin K group who achieved objective response (22.5 +/- 12.2; median: 21; range 11-37 months) as compared to patients not achieving objective response (6.1 +/- 4.6; median: 5; range 1-16 months) (P = 0.0.002). Portal vein thrombosis resolved with complete patency in one (4.35%) patient. Treatment with high dose vitamin K produces objective response in 17% patients with improved survival in patients achieving objective response; however, it does not affect the overall survival.

  19. Cooperative binding mitigates the high-dose hook effect.

    Science.gov (United States)

    Roy, Ranjita Dutta; Rosenmund, Christian; Stefan, Melanie I

    2017-08-14

    The high-dose hook effect (also called prozone effect) refers to the observation that if a multivalent protein acts as a linker between two parts of a protein complex, then increasing the amount of linker protein in the mixture does not always increase the amount of fully formed complex. On the contrary, at a high enough concentration range the amount of fully formed complex actually decreases. It has been observed that allosterically regulated proteins seem less susceptible to this effect. The aim of this study was two-fold: First, to investigate the mathematical basis of how allostery mitigates the prozone effect. And second, to explore the consequences of allostery and the high-dose hook effect using the example of calmodulin, a calcium-sensing protein that regulates the switch between long-term potentiation and long-term depression in neurons. We use a combinatorial model of a "perfect linker protein" (with infinite binding affinity) to mathematically describe the hook effect and its behaviour under allosteric conditions. We show that allosteric regulation does indeed mitigate the high-dose hook effect. We then turn to calmodulin as a real-life example of an allosteric protein. Using kinetic simulations, we show that calmodulin is indeed subject to a hook effect. We also show that this effect is stronger in the presence of the allosteric activator Ca 2+ /calmodulin-dependent kinase II (CaMKII), because it reduces the overall cooperativity of the calcium-calmodulin system. It follows that, surprisingly, there are conditions where increased amounts of allosteric activator actually decrease the activity of a protein. We show that cooperative binding can indeed act as a protective mechanism against the hook effect. This will have implications in vivo where the extent of cooperativity of a protein can be modulated, for instance, by allosteric activators or inhibitors. This can result in counterintuitive effects of decreased activity with increased concentrations of

  20. Radiation processing and high-dose dosimetry at ANSTO

    International Nuclear Information System (INIS)

    Gant, G.J.; Saunders, M.; Banos, C.; Mo, L.; Davies, J.; Evans, O.

    2001-01-01

    The Radiation Technology group at ANSTO is part of the Physics Division and provides services and advice in the areas of gamma irradiation and high-dose dosimetry. ANSTO's irradiation facilities are designed for maximum dose uniformity and provide a precision irradiation service unique in Australia. Radiation Technology makes and sells reference and transfer standard dosimeters which are purchased by users and suppliers of commercial irradiation services in Australia and the Asia-Pacific region. A calibration service is also provided for dosimeters purchased from other suppliers

  1. An evaluation of high-dose jobs for ALARA improvement

    International Nuclear Information System (INIS)

    Mun, J. H.; Kim, H. S.

    1997-01-01

    It is well known that about 70 percent of occupational dose have incurred from maintenance jobs at outage period. To reduce occupational dose, first, the high-dose jobs at the outage period should be identified and evaluated. For this, the database program is used, which contains the ORE data of reference plants, Kori Units 3 and 4. As a result, it is found that the jobs related to steam generator are the highest dose jobs in terms of collective ORE dose. From the analysis of the job procedures of those jobs, the ALARA improvements are also derived

  2. Australian high-dose-rate brachytherapy protocols for gynaecological malignancy

    International Nuclear Information System (INIS)

    MacLeod, C.; Dally, M.; Stevens, M.; Thornton, D.; Carruthers, S.; Jeal, P.

    2001-01-01

    There is no consensus over the optimal dose fractionation schedules for high-dose-rate (HDR) brachytherapy used for gynaecological malignancy. In Australian public hospital departments of radiation oncology, HDR brachytherapy for gynaecological cancer is being more commonly used. A survey of public departments that are using this technology, or that plan to introduce this technology, was performed. Their current protocols are presented. In general, protocols are similar biologically; however, the practical aspects such as the number of fractions given do vary and may reflect resource restrictions or, alternatively, differences in interpretations of the literature and of the best protocols by clinicians. Copyright (2001) Blackwell Science Pty Ltd

  3. Prehospital high-dose sublingual nitroglycerin rarely causes hypotension.

    Science.gov (United States)

    Clemency, Brian M; Thompson, Jeffrey J; Tundo, Gina N; Lindstrom, Heather A

    2013-10-01

    High-dose intravenous nitroglycerin is a common in-hospital treatment for respiratory distress due to congestive heart failure (CHF) with hypertension. Intravenous (IV) nitroglycerin administration is impractical in the prehospital setting. In 2011, a new regional Emergency Medical Services (EMS) protocol was introduced allowing advanced providers to treat CHF with high-dose oral nitroglycerin. The protocol calls for patients to be treated with two sublingual tabs (0.8 mg) when systolic blood pressure (SBP) was >160 mm Hg, or three sublingual tabs (1.2 mg) when SBP was >200 mm Hg, every five minutes as needed. Hypothesis/Problem To assess the protocol's safety, the incidence of hypotension following prehospital administration of multiple simultaneous nitroglycerin (MSN) tabs by EMS providers was studied. This study was a retrospective cohort study of patients from a single commercial EMS agency over a 6-month period. Records from patients with at least one administration of MSN were reviewed. For each administration, the first documented vital signs pre- and post-administration were compared. Administrations were excluded if pre- or post-administration vital signs were missing. One hundred case-patients had at least one MSN administration by an advanced provider during the study period. Twenty-five case-patients were excluded due to incomplete vital signs. Seventy-five case-patients with 95 individual MSN administrations were included for analysis. There were 65 administrations of two tabs, 29 administrations of three tabs, and one administration of four tabs. The mean change in SBP following MSN was -14.7 mm Hg (SD = 30.7; range, +59 to -132). Three administrations had documented systolic hypotension in the post-administration vital signs (97/71, 78/50 and 66/47). All three patients were over 65 years old, were administered two tabs, had documented improved respiratory status, and had repeat SBP of at least 100. The incidence of hypotension following MSN

  4. High-dose irradiated food: Current progress, applications, and prospects

    Science.gov (United States)

    Feliciano, Chitho P.

    2018-03-01

    Food irradiation as an established and mature technology has gained more attention in the food industry for ensuring food safety and quality. Primarily used for phytosanitary applications, its use has been expanded for developing various food products for varied purposes (e.g. ready-to-eat & ready-to-cook foods, hospital diets, etc.). This paper summarized and analyzed the recent progress and application of high-dose irradiation and discussed its prospects in the field of food product development, its safety and quality.

  5. Establishment of a dosimetric system for high doses using glasses

    International Nuclear Information System (INIS)

    Correa Quezada, Valeria de la Asuncion

    1997-01-01

    A routine dosimetric system was developed using commercial glass samples. The dosimetric characteristics of national and imported samples were studied: batch uniformity, response repeatability, reutilization, absorbed dose response, detection range, response stability as a function of absorbed dose, storage temperature and thermal treatments pre- and post-irradiation, using the optical absorption technique. As an application, the dosimetric system was tested in a flower irradiation process at IPEN. All the obtained results show the usefulness of the proposed system for high dose dosimetry. (author)

  6. High-dose simultaneously integrated breast boost using intensity-modulated radiotherapy and inverse optimization

    International Nuclear Information System (INIS)

    Hurkmans, Coen W.; Meijer, Gert J.; Vliet-Vroegindeweij, Corine van; Sangen, Maurice J. van der; Cassee, Jorien

    2006-01-01

    Purpose: Recently a Phase III randomized trial has started comparing a boost of 16 Gy as part of whole-breast irradiation to a high boost of 26 Gy in young women. Our main aim was to develop an efficient simultaneously integrated boost (SIB) technique for the high-dose arm of the trial. Methods and Materials: Treatment planning was performed for 5 left-sided and 5 right-sided tumors. A tangential field intensity-modulated radiotherapy technique added to a sequentially planned 3-field boost (SEQ) was compared with a simultaneously planned technique (SIB) using inverse optimization. Normalized total dose (NTD)-corrected dose volume histogram parameters were calculated and compared. Results: The intended NTD was produced by 31 fractions of 1.66 Gy to the whole breast and 2.38 Gy to the boost volume. The average volume of the PTV-breast and PTV-boost receiving more than 95% of the prescribed dose was 97% or more for both techniques. Also, the mean lung dose and mean heart dose did not differ much between the techniques, with on average 3.5 Gy and 2.6 Gy for the SEQ and 3.8 Gy and 2.6 Gy for the SIB, respectively. However, the SIB resulted in a significantly more conformal irradiation of the PTV-boost. The volume of the PTV-breast, excluding the PTV-boost, receiving a dose higher than 95% of the boost dose could be reduced considerably using the SIB as compared with the SEQ from 129 cc (range, 48-262 cc) to 58 cc (range, 30-102 cc). Conclusions: A high-dose simultaneously integrated breast boost technique has been developed. The unwanted excessive dose to the breast was significantly reduced

  7. High-doses of proton pump inhibitors in refractory gastro-intestinal cancer: A case series and the state of art.

    Science.gov (United States)

    Falcone, Rosa; Roberto, Michela; D'Antonio, Chiara; Romiti, Adriana; Milano, Annalisa; Onesti, Concetta Elisa; Marchetti, Paolo; Fais, Stefano

    2016-12-01

    In recent years, proton pump inhibitors (PPIs) have been investigated at high-dose to modulate tumour microenvironment acidification thus restoring chemotherapeutic sensitivity. Moreover, several clinical data supports the role of cytotoxic drugs at low-dose continuously delivered as anticancer therapy. Clinical records of three patients affected with gastrointestinal cancer refractory to standard treatments, who had received a combination of high-dose rabeprazole and metronomic chemotherapy were reviewed. The first case, a 78-year-old man was treated for lung metastasis from colon adenocarcinoma. The second case, a 73-year-old man was treated for metastatic rectal cancer to the liver. The third one, a 68-year-old man, underwent the combination regimen for colon cancer with lung, liver and peritoneal metastases. Despite the failure of previous standard chemotherapy for metastatic disease, good clinical outcome was shown in these patients treated with an unconventional association of high-dose PPIs and metronomic chemotherapy. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  8. Management of chemotherapy induced diarrhea (abstract)

    International Nuclear Information System (INIS)

    Qureshi, A.M.

    1998-01-01

    Diarrhoea is seen with many tumors and following several chemotherapy regimen esp. those containing 5-fluorouracil and high dose folinic acid it causes debility even death, delays cancer treatment, reduces compliance increases cost. It causes dehydration, renal failure volume depletion. Quality of life is worsened and hospitalization may be needed in multifactorial, with secretion; absorption imbalance due to mucosal damage, necrosis or inflammation. Local infection is set up by opportunistic organism and cell necrosis. The large volume of fluid and electrolytes overwhelms colonic absorptive capacity. Agent usually used for treatment is opioids (such as Diphenoxylate / Loperamide]. Bismuth (for inflammatory diarrhea). NSAIDs or alpha 2-agonists. For optimal management, the cause and severity should be assessed and treatment planned. Advice is given about certain dietary restraints and avoidance of some drugs. Fever, infection, dehydration and electrolyte losses are treated, pain relieved. Diphenoxylate / Loperamide (later is more effective; 4 mg, STAT, then 2mg every 4 hours or even 2 hourly) may be used. It is moderately effective in CID. Octreotide is useful in carcinoid. VIPoma, AIDS idiopathic secretary diarrhea, ileostomy, dumping syndrome. It acts directly on epithelial cells to reduce secretin, motilin pancreatic polypeptide. It slows transit time, reduces fluid and electrolyte secretin, increases absorption of electrolytes. It is effective in 5 FU and high dose chemotherapy with a 90% response rates seen after 3 days treatment. High Dose Chemotherapy and total body irradiation - induced diarrhea usually resolves within 72 hours. (author)

  9. The influence of high doses of radiation in citrine stones

    International Nuclear Information System (INIS)

    Teixeira, M. I.; Caldas, L. V. E.

    2014-08-01

    The possibility of using samples of Brazilian stones as quartz, amethyst, topaz, jasper, etc. for high-dose dosimetry has been studied in recent years at IPEN, using the techniques of optical absorption (Oa), thermoluminescent (Tl), optically stimulated luminescence (OSL) and resonance paramagnetic electron (EPR). In this work, the Tl properties of citrine samples were studied. They were exposed to different doses of gamma radiation ( 60 Co). The natural citrine stone was extracted from a mine in Minas Gerais state, Brazil; it is a tecto silicate ranked as one of three-dimensional structure, showing clear yellow to golden brown color. The natural citrine stone is classified as quartz (SiO 2 ), and it has a lower symmetry and more compact reticulum. The Tl emission curve showed two peaks at 160 grades C and 220 grades C. To remove the Tl peak (160 grades C) of the sintered citrine pellet glow curves, different thermal treatments were tested during several time intervals. The Tl dose-response curve between 50 Gy and 100 kGy, the reproducibility of Tl response and the lower detection dose were obtained. The results show that citrine may be useful as high-dose detectors. (Author)

  10. High-dose contrast-enhanced MRI in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Koudriavtseva, T. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Pozzilli, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Di Biasi, C. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Iannilli, M. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Trasimeni, G. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Gasperini, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Argentino, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Gualdi, G.F. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy)

    1996-05-01

    Contrast-enhanced MRI is effective for assessing disease activity in multiple sclerosis (MS) and may provide an outcome measure for testing the efficacy of treatment in clinical trials. To compare the sensitivity of high-dose gadolinium-HP-DO3A with that of a standard dose of gadolinium-DTPA, we studied 16 patients with relapsing-remitting MS in the acute phase of the disease. Each underwent two MRI examinations within at most 48 h. The initial MRI study was with a standard dose of gadolinium-DTPA (0.1 mmol/kg), and the second one an experimental dose of gadolinium-HP-DO3A (0.3 mmol/kg). No adverse effects were attributed to the contrast media. The high-dose study revealed more enhancing lesions than the standard-dose study (56 vs 38). This difference was found to be more relevant for infratentorial and small lesions. Furthermore, with the higher dose, there was a marked qualitative improvement in the visibility and delineation of the lesions. (orig.). With 4 figs., 2 tabs.

  11. TL response of citrine samples for high-dose dosimetry

    International Nuclear Information System (INIS)

    Teixeira, Maria Ines; Caldas, Linda V.E.

    2011-01-01

    The possibility of using samples of Brazilian stones as quartz, amethyst, topaz, etc. for high-dose dosimetry has been studied in recent years at IPEN, using the thermoluminescence technique (TL). In this work, the TL properties of citrine samples were studied. They were exposed to different doses of gamma radiation ( 60 Co). The natural citrine stone was extracted from a mine in Minas Gerais state, Brazil; it is a tectosilicate ranked as one of three-dimensional structure, showing clear yellow to golden brown color. The natural citrine stone is classified as quartz (SiO 2 ), and it has a lower symmetry and more compact reticulum. The citrine stone samples were powdered, and the selected grains were mixed with Teflon in the proportion 2 (Teflon):1 (Citrine). The mixture was pressed and sintered for production of Citrine -Teflon pellets of 50 mg. The TL emission curve showed two peaks at 160 deg C and 220 deg C. To remove the TL peak (160 deg C) of the sintered citrine pellet glow curves, different thermal treatments were tested during several time intervals. The TL dose-response curve between 50 Gy and 100 kGy, the reproducibility of TL response and the lower detection dose were obtained. The preliminary results show that citrine may be useful for high-dose dosimetry. (author)

  12. Spectroscopic gamma camera for use in high dose environments

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, Yuichiro, E-mail: yuichiro.ueno.bv@hitachi.com [Research and Development Group, Hitachi, Ltd., Hitachi-shi, Ibaraki-ken 319-1221 (Japan); Takahashi, Isao; Ishitsu, Takafumi; Tadokoro, Takahiro; Okada, Koichi; Nagumo, Yasushi [Research and Development Group, Hitachi, Ltd., Hitachi-shi, Ibaraki-ken 319-1221 (Japan); Fujishima, Yasutake; Kometani, Yutaka [Hitachi Works, Hitachi-GE Nuclear Energy, Ltd., Hitachi-shi, Ibaraki-ken (Japan); Suzuki, Yasuhiko [Measuring Systems Engineering Dept., Hitachi Aloka Medical, Ltd., Ome-shi, Tokyo (Japan); Umegaki, Kikuo [Faculty of Engineering, Hokkaido University, Sapporo-shi, Hokkaido (Japan)

    2016-06-21

    We developed a pinhole gamma camera to measure distributions of radioactive material contaminants and to identify radionuclides in extraordinarily high dose regions (1000 mSv/h). The developed gamma camera is characterized by: (1) tolerance for high dose rate environments; (2) high spatial and spectral resolution for identifying unknown contaminating sources; and (3) good usability for being carried on a robot and remotely controlled. These are achieved by using a compact pixelated detector module with CdTe semiconductors, efficient shielding, and a fine resolution pinhole collimator. The gamma camera weighs less than 100 kg, and its field of view is an 8 m square in the case of a distance of 10 m and its image is divided into 256 (16×16) pixels. From the laboratory test, we found the energy resolution at the 662 keV photopeak was 2.3% FWHM, which is enough to identify the radionuclides. We found that the count rate per background dose rate was 220 cps h/mSv and the maximum count rate was 300 kcps, so the maximum dose rate of the environment where the gamma camera can be operated was calculated as 1400 mSv/h. We investigated the reactor building of Unit 1 at the Fukushima Dai-ichi Nuclear Power Plant using the gamma camera and could identify the unknown contaminating source in the dose rate environment that was as high as 659 mSv/h.

  13. High-dose contrast-enhanced MRI in multiple sclerosis

    International Nuclear Information System (INIS)

    Koudriavtseva, T.; Pozzilli, C.; Di Biasi, C.; Iannilli, M.; Trasimeni, G.; Gasperini, C.; Argentino, C.; Gualdi, G.F.

    1996-01-01

    Contrast-enhanced MRI is effective for assessing disease activity in multiple sclerosis (MS) and may provide an outcome measure for testing the efficacy of treatment in clinical trials. To compare the sensitivity of high-dose gadolinium-HP-DO3A with that of a standard dose of gadolinium-DTPA, we studied 16 patients with relapsing-remitting MS in the acute phase of the disease. Each underwent two MRI examinations within at most 48 h. The initial MRI study was with a standard dose of gadolinium-DTPA (0.1 mmol/kg), and the second one an experimental dose of gadolinium-HP-DO3A (0.3 mmol/kg). No adverse effects were attributed to the contrast media. The high-dose study revealed more enhancing lesions than the standard-dose study (56 vs 38). This difference was found to be more relevant for infratentorial and small lesions. Furthermore, with the higher dose, there was a marked qualitative improvement in the visibility and delineation of the lesions. (orig.). With 4 figs., 2 tabs

  14. Radiation safety program in a high dose rate brachytherapy facility

    International Nuclear Information System (INIS)

    Rodriguez, L.V.; Hermoso, T.M.; Solis, R.C.

    2001-01-01

    The use of remote afterloading equipment has been developed to improve radiation safety in the delivery of treatment in brachytherapy. Several accidents, however, have been reported involving high dose-rate brachytherapy system. These events, together with the desire to address the concerns of radiation workers, and the anticipated adoption of the International Basic Safety Standards for Protection Against Ionizing Radiation (IAEA, 1996), led to the development of the radiation safety program at the Department of Radiotherapy, Jose R. Reyes Memorial Medical Center and at the Division of Radiation Oncology, St. Luke's Medical Center. The radiation safety program covers five major aspects: quality control/quality assurance, radiation monitoring, preventive maintenance, administrative measures and quality audit. Measures for evaluation of effectiveness of the program include decreased unnecessary exposures of patients and staff, improved accuracy in treatment delivery and increased department efficiency due to the development of staff vigilance and decreased anxiety. The success in the implementation required the participation and cooperation of all the personnel involved in the procedures and strong management support. This paper will discuss the radiation safety program for a high dose rate brachytherapy facility developed at these two institutes which may serve as a guideline for other hospitals intending to install a similar facility. (author)

  15. ELDRS Characterization for a Very High Dose Mission

    Science.gov (United States)

    Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

    2010-01-01

    Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

  16. Methodology of high dose research in medical radiodiagnostic

    International Nuclear Information System (INIS)

    Barboza, Adriana E.; Martins, Cintia P. de S.

    2013-01-01

    This work has as main purpose to study occupational exposure in diagnostic radiology in medical cases of high doses recorded in 2011 at the national level . These doses were recorded by monitoring individual of the occupationally exposed individuals (OEI's). This monitoring of the doses received by ionizing radiation has as main objective to ensure that the principle of dose limitation is respected. In this study it were evaluated doses of 372 OEI's radiology in different Brazilian states. Doses were extracted from the database of Sector Management Doses of the Institute for Radioprotection and Dosimetry - IRD/CNEN-RJ, Brazil. The information from the database provide reports of doses from several states, which allows to quantify statistically, showing those with the highest doses in four areas: dose greater than or equal to 20 mSv apron and chest and dose greater than or equal to 100 mSv apron and chest. The identification of these states allows the respective Sanitary Surveillance (VISA), be aware of the events and make plans to reduce them. This study clarified the required procedures when there is a record of high dose emphasizing the importance of using protective radiological equipment, dosimeter and provide a safety environment work by maintaining work equipment. Proposes the ongoing training of professionals, emphasizing the relevance of the concepts of radiation protection and the use of the questionnaire with their investigative systematic sequence, which will allow quickly and efficiently the success the investigations

  17. Dosimetric properties of commercial glasses and sand for high doses

    International Nuclear Information System (INIS)

    Teixeira, Maria Ines

    2004-01-01

    Commercial glasses (transparent and colored) produced by Cebrace, Brazil, Sao Paulo, and sand samples of different Brazilian beaches were studied, due to their low cost and easy handling, to verify the possibility of their use in high dose dosimetry. The main dosimetric characteristics were determined using a densitometer, a spectrophotometer, a thermoluminescent (TL) reader and an electronic paramagnetic resonance system. The gamma irradiations were carried out using a Gamma-Cell 220 and a panoramic source ( 60 Co) of IPEN. An optical absorption band was observed at 420 nm in the glass samples. The TL glow curves presented peaks at 205 deg C, 135 deg C, 150 deg C and 145 deg C for the transparent, bronze, brown and green glass samples, respectively. All EPR spectra of the glasses showed Fe 3+ characteristic signals at g = 4.27 and 2.01. The gamma irradiated sand samples presented two peaks at 110 deg C and 170 deg C and an EPR signal at g= 1.999. However, these materials present a pronounced thermal fading at room temperature after irradiation. With the objective to minimize this thermal fading, both glass and sand samples were submitted to different pre- and post-irradiation thermal treatments. The glass and sand samples showed the possibility of utilization for high dose dosimetry and as Yes/No irradiation detectors. (author)

  18. Multifocal Electroretinography after High Dose Chloroquine Therapy for Malaria

    Directory of Open Access Journals (Sweden)

    Aline Correa de Carvalho

    2013-01-01

    Full Text Available Purpose: To investigate changes in multifocal electroretinography (mfERG parameters associated with high dose chloroquine therapy for treatment of malaria in the Amazonia region of Brazil. Methods: Forty-eight subjects who had received chloroquine treatment for single or multiple malaria infections with a cumulative dose ranging from 1,050 to 27,000mg were included. The control group consisted of 37 healthy aged-matched subjects. Data was collected on amplitude and implicit time of the N1, P1 and N2 waves in the central macular hexagon (R1 and in five concentric rings at different retinal eccentricities (R2-R6. Results: No significant difference was observed in any mfERG parameter between chloroquine treated patients and control subjects. A comparison with previous data obtained from patients with rheumatologic disorders in the same region of Brazil who had received larger cumulative doses of chloroquine and had displayed mfERG changes, indicated that retinal toxicity seems to be dependent on cumulative dose. Conclusion: Lack of mfERG changes in the current study suggests that intensive high dose chloroquine therapy for treatment of malaria is not associated with retinal toxicity.

  19. The influence of high doses of radiation in citrine stones

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, M. I. [Universidade Nove de Julho - UNINOVE, Rua Vergueiro 235/249, 01504-001 Sao Paulo (Brazil); Caldas, L. V. E., E-mail: miteixeira@ipen.br [Instituto de Pesquisas Energeticas e Nucleares / CNEN, Av. Lineu Prestes 2242, Cidade Universitaria, 05508-000 Sao Paulo (Brazil)

    2014-08-15

    The possibility of using samples of Brazilian stones as quartz, amethyst, topaz, jasper, etc. for high-dose dosimetry has been studied in recent years at IPEN, using the techniques of optical absorption (Oa), thermoluminescent (Tl), optically stimulated luminescence (OSL) and resonance paramagnetic electron (EPR). In this work, the Tl properties of citrine samples were studied. They were exposed to different doses of gamma radiation ({sup 60}Co). The natural citrine stone was extracted from a mine in Minas Gerais state, Brazil; it is a tecto silicate ranked as one of three-dimensional structure, showing clear yellow to golden brown color. The natural citrine stone is classified as quartz (SiO{sub 2}), and it has a lower symmetry and more compact reticulum. The Tl emission curve showed two peaks at 160 grades C and 220 grades C. To remove the Tl peak (160 grades C) of the sintered citrine pellet glow curves, different thermal treatments were tested during several time intervals. The Tl dose-response curve between 50 Gy and 100 kGy, the reproducibility of Tl response and the lower detection dose were obtained. The results show that citrine may be useful as high-dose detectors. (Author)

  20. Audits in high dose rate brachytherapy in Brazil

    International Nuclear Information System (INIS)

    Marechal, M.H.; Rosa, L.A.; Velasco, A.; Paiva, E. de; Goncalves, M.; Castelo, L.C.

    2002-01-01

    The lack of well established dosimetry protocols for HDR sources is a point of great concern regarding the uniformity of procedures within a particular country. The main objective of this paper is to report the results of an implementation of the audit program in dosimetry of high dose rate brachytherapy sources used by the radiation therapy centers in Brazil. In Brazil, among 169 radiotherapy centers, 35 have HDR brachytherapy systems. This program started in August 2001 and until now eight radiotherapy services were audited. The audit program consists of the visit in loco to each center and the evaluation of the intensity of the source with a well type chamber specially design for HDR 192 Ir sources. The measurements was carried out with a HDR1000PLUS Brachytherapy Well Type Chamber and a MAX 4000 Electrometer, both manufactured by Standard Imaging Inc. The chamber was calibrated in air kerma strength by the Accredited Dosimetry Calibration Laboratory, Department of Medical Physics, University of Wisconsin in the USA. The same chamber was calibrated in Brazil using a 192 lr high dose rate source whose intensity was determined by 60 Co gamma rays and 250 kV x rays interpolation methodology. The Nk of 60 Co and 250 kV x rays were provided by the Brazilian National Standard Laboratory for Ionizing Radiation (LMNRI)

  1. Stock selection of high-dose-irradiation-resistant materials for filter press under high-dose irradiation operation

    International Nuclear Information System (INIS)

    Ishiyama, Shintaro; Minami, Mamoru; Hara, Kouji; Yamashita, Manabu

    2015-01-01

    In a volume reduction process for the decontamination of contained soil, the performance degradation of a filter press is expected owing to material deterioration under high-dose irradiation. Eleven-stock selection of candidate materials including polymers, fibers and rubbers for the filter press was conducted to achieve a high performance of volume reduction of contaminated soil and the following results were derived. Crude rubber and nylon were selected as prime candidates for packing, diaphragm and filter plate materials. Polyethylene was also selected as a prime candidate for the filter cloth material. (author)

  2. Reduced supportive capacity of bone marrow stroma upon chemotherapy is mediated via changes in glycosaminoglycan profile

    NARCIS (Netherlands)

    Zweegman, Sonja; Kessler, Floortje L.; Kerkhoven, Ron M.; Heimerikx, Mike; Celie, Johanna W. A. M.; Janssen, Jeroen J. W. M.; Huijgens, Peter C.; Drager, Angelika M.; van den Born, Jacob

    High dose chemotherapy and radiation have been found to impair the hematopoiesis-supportive capacity of bone marrow stroma. We now provide evidence for an important role of chemotherapy-induced alterations in stromal glycosaminoglycans (GAGs) in reduction of the supportive properties of stromal

  3. High Doses Gamma Radiolysis of PVC: Mechanisms of Degradation

    International Nuclear Information System (INIS)

    Colombani, J.

    2006-01-01

    PVC radiolysis leads to the formation of various degradation products: radicals, gas, oxidized products or polyenes. In order to predict the formation of the degradation products with regard to irradiation and ageing parameters, it is important to improve the understanding of the radiolysis mechanisms of PVC. Thus, we used several analytical techniques (Electron Spin Resonance, Fourier Transform Infrared spectroscopy, Nuclear Magnetic Resonance, Size Exclusion Chromatography) to get information on PVC samples irradiated at high doses (up to 4MGy) under different conditions. Gamma irradiation induces the formation of various radicals into PVC. Older studies were generally focused on the effect of low dose and/or low temperature irradiations on PVC. We present here ESR signals of PVC irradiated at high doses and at room temperature. We show that peroxyl radicals are producted by radiolysis under aerobe conditions and that polyenyl radicals are formed under anaerobe conditions. PVC radiolysis induces gas production and especially hydrogen chloride. Production of hydrogen chloride is well known until 1 MGy. We have studied by FTIR, the evolution of the quantity of HCl produced until 4 MGy. We show that higher irradiation dose leads to the lower radiolytic yield of HCl (G(HCl)). Moreover, G(HCl) obtained in aerobe conditions is about fourfold as great as G(HCl) observed in anaerobe radiolysis. Propagation and termination reactions induce degradation products: polyene sequences and crosslinking reactions are observed under anaerobe conditions; oxidized products with addition of chain scissions are formed under aerobe conditions. Although the literature about PVC radiolysis is rich, the main reacting pathways are not well established. Moreover the high doses studies are almost non-existent. We show by FTIR that aerobe radiolysis induces formation of ketons and acids. NMR experiments confirme these results but also focuse on small acids formed (with 2, 3 or 4 carbons). The

  4. High-dose radioiodine therapy of Graves disease

    International Nuclear Information System (INIS)

    Solodky, V.; Fomin, D.; Pestritskaya, E.

    2015-01-01

    Full text of publication follows. Objectives: to estimate the effectiveness and safety of the disease treatment under different modes of applying RIT. Materials and methods: 67 patients with the thyrotoxicosis condition associated with Graves disease were researched. The patients were divided into 2 groups: a control group with 25 people (18 women and 7 men), who underwent a low-dose therapy of 150-500 MBq; and a main group of 42 people (32 women and 10 men), who underwent a high-dose therapy of 550 and 800 MBq. The volume of thyroid prior to the treatment made up 23.8 ± 20 ml in the main group and 30.2 ± 23 ml in the control one. The average age in the high-dose group was 44.6 ±23 years old and in the low-dose -47.2 ± 24 years old. In terms of the hormone level before the RIT, 52% of the main group patients experienced euthyroidism, while 48% - thyrotoxicosis. The corresponding indices in the control group were 42% and 58% respectively. The cessation of the thyreostatic therapy came on 5. to 21. day prior to the treatment, with the average of 14 ±7 days in both groups. The diagnosis of the disease was based on ultrasonography, planar scintigraphy, the hormone level and antibody titer. The performance was assessed through the attainment of hypo-thyrosis and the transition to a substitutive hormonal therapy with L-thyroxine in 6 months or more. The attainment of euthyroidism was seen as a partial effect due to a possibility of relapse. Results: in 6 months a positive result in the form of hypo-thyrosis was achieved for 39 patients in the main group, which accounted for 93%, and 3 patients (7%) experienced euthyroidism. No symptomatic thyrotoxicosis relapses were revealed. In the control group, hypo-thyrosis was achieved by 18 patients, which accounted for 72%; euthyroidism came up to 12%; 4 patients needed a refresher course of RIT, which made up 16% of the group. 93% of the main group patients tolerated the treatment favourably. 3 patients complained of the

  5. Routine quality control of high dose rate brachytherapy equipment

    International Nuclear Information System (INIS)

    Guzman Calcina, Carmen S.; Almeida, Adelaide de; Rocha, Jose R. Oliveira

    2001-01-01

    A Quality Assurance program should be installed also for High Dose Rate brachytherapy, in the order to achieve a correct dose administration to the patient and for the safety to those involved directly with the treatment. The work presented here has the following purposes: Analyze the types of equipment tests presented by the official protocols (TG40, TG56 e ARCAL XXX), evaluate the brachytherapy routine tests of protocols from various national and international radiotherapy services and compare the latter with those presented in the official protocols. As a result, we conclude the following: TG56 presents a higher number of tests when compared to the other official protocols and most of the tests presented by the analyzed services are present in TG56. A suggestion for a basic protocol is presented, emphasizing the periodicity and tolerance level of each of the tests. (author)

  6. Surface sputtering in high-dose Fe ion implanted Si

    International Nuclear Information System (INIS)

    Ishimaru, Manabu

    2007-01-01

    Microstructures and elemental distributions in high-dose Fe ion implanted Si were characterized by means of transmission electron microscopy and Rutherford backscattering spectroscopy. Single crystalline Si(0 0 1) substrates were implanted at 350 deg. C with 120 keV Fe ions to fluences ranging from 0.1 x 10 17 to 4.0 x 10 17 /cm 2 . Extensive damage induced by ion implantation was observed inside the substrate below 1.0 x 10 17 /cm 2 , while a continuous iron silicide layer was formed at 4.0 x 10 17 /cm 2 . It was found that the spatial distribution of Fe projectiles drastically changes at the fluence between 1.0 x 10 17 and 4.0 x 10 17 /cm 2 due to surface sputtering during implantation

  7. measurement of high dose radiation using yellow perspex dosimeter

    International Nuclear Information System (INIS)

    Thamrin, M Thoyib; Sofyan, Hasnel

    1996-01-01

    Measurement of high dose radiation using yellow perspex dosemeter has been carried out. Dose range used was between 0.1 to 3.0 kGy. Measurement of dose rate against Fricke dosemeter as a standard dose meter From the irradiation of Fricke dosemeter with time variation of 3,6,9,12,15 and 18 minute, it was obtained average dose rate of 955.57 Gy/hour, linear equation of dose was Y= 2.333+15.776 X with its correlation factor r = 0.9999. Measurement result using yellow perspex show that correlation between net optical density and radiation dose was not linear with its equation was ODc exp. [Bo + In(dose).Bi] Value of Bo = -0.215 and Bi=0.5020. From the experiment it was suggested that routine dosimeter (yellow perspex) should be calibrated formerly against standard dosemeters

  8. High Fidelity Ion Beam Simulation of High Dose Neutron Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Was, Gary; Wirth, Brian; Motta, Athur; Morgan, Dane; Kaoumi, Djamel; Hosemann, Peter; Odette, Robert

    2018-04-30

    Project Objective: The objective of this proposal is to demonstrate the capability to predict the evolution of microstructure and properties of structural materials in-reactor and at high doses, using ion irradiation as a surrogate for reactor irradiations. “Properties” includes both physical properties (irradiated microstructure) and the mechanical properties of the material. Demonstration of the capability to predict properties has two components. One is ion irradiation of a set of alloys to yield an irradiated microstructure and corresponding mechanical behavior that are substantially the same as results from neutron exposure in the appropriate reactor environment. Second is the capability to predict the irradiated microstructure and corresponding mechanical behavior on the basis of improved models, validated against both ion and reactor irradiations and verified against ion irradiations. Taken together, achievement of these objectives will yield an enhanced capability for simulating the behavior of materials in reactor irradiations

  9. High-dose erythropoietin in patients with progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Schreiber, Karen; Magyari, Melinda; Sellebjerg, Finn

    2017-01-01

    BACKGROUND: Erythropoietin (EPO) is a part of an endogenous neuroprotective system in the brain and may address pathophysiological mechanisms in progressive multiple sclerosis (MS). OBJECTIVE: To evaluate a treatment effect of EPO on progressive MS. METHODS: This was a single-center, randomized......, double-blind, placebo-controlled phase 2 trial, in which 52 patients with secondary or primary progressive MS were allocated to treatment with recombinant EPO (48,000 IU) or placebo, administered intravenously 17 times during 24 weeks. Patients had an Expanded Disability Status Score (EDSS) from 4 to 6......: This study provides class II evidence that treatment with high-dose EPO is not an effective treatment in patients with moderately advanced progressive MS....

  10. Safety handling manual for high dose rate remote afterloading system

    International Nuclear Information System (INIS)

    1999-01-01

    This manual is mainly for safety handling of 192 Ir-RALS (remote afterloading system) of high dose rate and followings were presented: Procedure and document format for the RALS therapy and for handling of its radiation source with the purpose of prevention of human errors and unexpected accidents, Procedure for preventing errors occurring in the treatment schedule and operation, and Procedure and format necessary for newly introducing the system into a facility. Consistency was intended in the description with the quality assurance guideline for therapy with small sealed radiation sources made by JASTRO (Japan Society for Therapeutic Radiology and Oncology). Use of the old type 60 Co-RALS was pointed out to be a serious problem remained and its safety handling procedure was also presented. (K.H.)

  11. Pharmacokinetics of high-dose intravenous melatonin in humans

    DEFF Research Database (Denmark)

    Andersen, Lars P H; Werner, Mads U; Rosenkilde, Mette Marie

    2016-01-01

    This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60......, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments...... of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221...

  12. Calibration of {sup 192}Ir high dose rate brachytherapy sources

    Energy Technology Data Exchange (ETDEWEB)

    Marechal, M H [Instituto de Radioprotecao e Dozimetria, Rio de Jainero (Brazil); Almeida, C.E. de [Laboratorio de Ciencias Radiologicas, UERL, Rio de Janeiro (Brazil); Sibata, C H [Roswell Park Cancer Inst., Buffalo, NY (United States)

    1996-08-01

    A method for calibration of high dose rate sources used in afterloading brachytherapy systems is described. The calibration for {sup 192}Ir is determined by interpolating {sup 60}Co gamma-rays and 250 kV x-rays calibration factors. All measurements were done using the same build up caps as described by Goetsch et al and recommended by AAPM. The attenuation correction factors were determined to be 0.9903, 0.9928 and 0.9993 for {sup 192}Ir, {sup 60}Co and 250 kV x-ray, respectively. A wall + cap thickness of 0.421 g.cm{sup -2} is recommended for all measurements to ensure electronic equilibrium for {sup 60}Co and {sup 192}Ir gamma-ray beams. A mathematical formalism is described for determination of (N{sub x}){sub Ir}. (author). 5 refs, 1 fig.

  13. Neuropsychological function in adults after high dose fractionated radiation therapy of skull base tumors

    International Nuclear Information System (INIS)

    Glosser, Guila; McManus, Pat; Munzenrider, John; Austin-Seymour, Mary; Fullerton, Barbara; Adams, Judy; Urie, Marcia M.

    1997-01-01

    Purpose: To evaluate the long term effects of high dose fractionated radiation therapy on brain functioning prospectively in adults without primary brain tumors. Methods and Materials: Seventeen patients with histologically confirmed chordomas and low grade chondrosarcomas of the skull base were evaluated with neuropsychological measures of intelligence, language, memory, attention, motor function and mood following surgical resection/biopsy of the tumor prior to irradiation, and then at about 6 months, 2 years and 4 years following completion of treatment. None received chemotherapy. Results: In the patients without tumor recurrence or radiation necrosis, there were no indications of adverse effects on cognitive functioning in the post-acute through the late stages after brain irradiation. Even in patients who received doses of radiation up to 66 Cobalt Gy equivalent through nondiseased (temporal lobe) brain tissue, memory and cognitive functioning remained stable for up to 5 years after treatment. A mild decline in psycho-motor speed was seen in more than half of the patients, and motor slowing was related to higher radiation doses in midline and temporal lobe brain structures. Conclusion: Results suggest that in adults, tolerance for focused radiation is relatively high in cortical brain structures

  14. Escalation to High Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease

    Science.gov (United States)

    Triplett, Brandon M.; Kuttab, Hani I.; Kang, Guolian; Leung, Wing

    2015-01-01

    Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those utilized in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial, 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. There was no observed increase in toxicity until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10–100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, while those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (p=0.008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose escalation strategy remains unclear, as outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD. PMID:26278046

  15. Escalation to High-Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease.

    Science.gov (United States)

    Triplett, Brandon M; Kuttab, Hani I; Kang, Guolian; Leung, Wing

    2015-12-01

    Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those used in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. Increased toxicity was not observed until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10 and 100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, whereas those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (P = .008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose-escalation strategy remains unclear, because outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  16. High-dose MeV electron irradiation of Si-SiO2 structures implanted with high doses Si+

    Science.gov (United States)

    Kaschieva, S.; Angelov, Ch; Dmitriev, S. N.

    2018-03-01

    The influence was studied of 22-MeV electron irradiation on Si-SiO2 structures implanted with high-fluence Si+ ions. Our earlier works demonstrated that Si redistribution is observed in Si+-ion-implanted Si-SiO2 structures (after MeV electron irradiation) only in the case when ion implantation is carried out with a higher fluence (1016 cm-2). We focused our attention on the interaction of high-dose MeV electron irradiation (6.0×1016 cm-2) with n-Si-SiO2 structures implanted with Si+ ions (fluence 5.4×1016 cm-2 of the same order magnitude). The redistribution of both oxygen and silicon atoms in the implanted Si-SiO2 samples after MeV electron irradiation was studied by Rutherford back-scattering (RBS) spectroscopy in combination with a channeling technique (RBS/C). Our results demonstrated that the redistribution of oxygen and silicon atoms in the implanted samples reaches saturation after these high doses of MeV electron irradiation. The transformation of amorphous SiO2 surface into crystalline Si nanostructures (after MeV electron irradiation) was evidenced by atomic force microscopy (AFM). Silicon nanocrystals are formed on the SiO2 surface after MeV electron irradiation. The shape and number of the Si nanocrystals on the SiO2 surface depend on the MeV electron irradiation, while their size increases with the dose. The mean Si nanocrystals height is 16-20 nm after irradiation with MeV electrons at the dose of 6.0×1016 cm-2.

  17. Types of chemotherapy

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000910.htm Types of chemotherapy To use the sharing features on this page, ... cancer.org/treatment/treatments-and-side-effects/treatment-types/chemotherapy/how-chemotherapy-drugs-work.html . Updated February 15, ...

  18. High dose rate brachytherapy for superficial cancer of the esophagus

    International Nuclear Information System (INIS)

    Maingon, Philippe; D'Hombres, Anne; Truc, Gilles; Barillot, Isabelle; Michiels, Christophe; Bedenne, Laurent; Horiot, Jean Claude

    2000-01-01

    Purpose: We analyzed our experience with external radiotherapy, combined modality treatment, or HDR brachytherapy alone to limited esophageal cancers. Methods and Materials: From 1991 to 1996, 25 patients with limited superficial esophagus carcinomas were treated by high dose rate brachytherapy. The mean age was 63 years (43-86 years). Five patients showed superficial local recurrence after external radiotherapy. Eleven patients without invasion of the basal membrane were staged as Tis. Fourteen patients with tumors involving the submucosa without spreading to the muscle were staged as T1. Treatment consisted of HDR brachytherapy alone in 13 patients, external radiotherapy and brachytherapy in 8 cases, and concomitant chemo- and radiotherapy in 4 cases. External beam radiation was administered to a total dose of 50 Gy using 2 Gy daily fractions in 5 weeks. In cases of HDR brachytherapy alone (13 patients), 6 applications were performed once a week. Results: The mean follow-up is 31 months (range 24-96 months). Twelve patients received 2 applications and 13 patients received 6 applications. Twelve patients experienced a failure (48%), 11/12 located in the esophagus, all of them in the treated volume. One patient presented an isolated distant metastasis. In the patients treated for superficial recurrence, 4/5 were locally controlled (80%) by brachytherapy alone. After brachytherapy alone, 8/13 patients were controlled (61%). The mean disease-free survival is 14 months (1-36 months). Overall survival is 76% at 1 year, 37% at 2 years, and 14% at 3 years. Overall survival for Tis patients is 24% vs. 20% for T1 (p 0.83). Overall survival for patients treated by HDR brachytherapy alone is 43%. One patient presented with a fistula with local failure after external radiotherapy and brachytherapy. Four stenosis were registered, two were diagnosed on barium swallowing without symptoms, and two required dilatations. Conclusion: High dose rate brachytherapy permits the treating

  19. High dose implantations of antimony for buried layer applications

    International Nuclear Information System (INIS)

    Gailliard, J.P.; Dupuy, M.; Garcia, M.; Roussin, J.C.

    1978-01-01

    Electrical and physical properties of high dose implantations of antimony in silicon have been studied for use in buried layer applications. The results have been obtained both on and oriented silicon wafers. Following implantations which lead to amorphization we perform an annealing at 600 0 C for 10 mn in order to recrystallize the layer. The observed electrical properties (μ, R) show that the concentration of electrically active antimony ions is greater than that predicted from the solubility of antimony in silicon. Further annealing (in the range 1050 0 - 1200 0 ) induces: firstly a precipitation of the Sb and secondly a diffusion and dissolution of the precipitates. There is a different evolution of the defects in the and silicon slices. T.E.M. reveals no defects in the wafers after one hour annealing at 1200 0 C, whereas defects and twins remain in wafers. Having obtained the evolution of R with time and temperature it is then determined the implantation and annealing conditions which lead to the low resistivity (R = 10) needed for buried layer applications. Results with very many industrially made devices are discussed

  20. Optimized dose distribution of a high dose rate vaginal cylinder

    International Nuclear Information System (INIS)

    Li Zuofeng; Liu, Chihray; Palta, Jatinder R.

    1998-01-01

    Purpose: To present a comparison of optimized dose distributions for a set of high-dose-rate (HDR) vaginal cylinders calculated by a commercial treatment-planning system with benchmark calculations using Monte-Carlo-calculated dosimetry data. Methods and Materials: Optimized dose distributions using both an isotropic and an anisotropic dose calculation model were obtained for a set of HDR vaginal cylinders. Mathematical optimization techniques available in the computer treatment-planning system were used to calculate dwell times and positions. These dose distributions were compared with benchmark calculations with TG43 formalism and using Monte-Carlo-calculated data. The same dwell times and positions were used for a quantitative comparison of dose calculated with three dose models. Results: The isotropic dose calculation model can result in discrepancies as high as 50%. The anisotropic dose calculation model compared better with benchmark calculations. The differences were more significant at the apex of the vaginal cylinder, which is typically used as the prescription point. Conclusion: Dose calculation models available in a computer treatment-planning system must be evaluated carefully to ensure their correct application. It should also be noted that when optimized dose distribution at a distance from the cylinder surface is calculated using an accurate dose calculation model, the vaginal mucosa dose becomes significantly higher, and therefore should be carefully monitored

  1. Shelf-stable food through high dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Placek, V. E-mail: pla@ujv.cz; Svobodova, V.; Bartonicek, B.; Rosmus, J.; Camra, M

    2004-10-01

    Irradiation of food with high doses (radappertization) is a way, how to prepare shelf-stable ready-to-eat food. The radappertization process requires that the food be heated at first to an internal temperature of at least 75 deg. C to inactivate autolytic enzyme, which could cause the spoilage during storage without refrigeration. In order to prevent radiation induced changes in sensory properties (off flavors, odors, undesirable color change, etc.) the food was vacuum packed and irradiated in frozen state at -30 deg. C or less to a minimum dose of 35 kGy. Such products have characteristics of fresh food prepared for eating even if they are stored for long time under tropical conditions. The wholesomeness (safety for consumption) has been confirmed during 40 years of testing. Within the NRI Rez 10 kinds of shelf-stable meat products have been prepared. The meat was cooked, vacuum packed in SiO{sub x}-containing pouch, freezed in liquid nitrogen and irradiated with electron beam accelerator. The microbial, chemical, and organoleptic properties have been tested.

  2. High-dose processing and application to Korean space foods

    Energy Technology Data Exchange (ETDEWEB)

    Song, Beom-Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Choi, Jong-il [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Kim, Jae-Hun [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Korea Astronaut Project Division, Korea Aerospace Research Institute, Daejeon 305-333 (Korea, Republic of); Byun, Myung-Woo [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Kang, Sang-Wook; Choi, Gi-Hyuk [Korea Astronaut Project Division, Korea Aerospace Research Institute, Daejeon 305-333 (Korea, Republic of); Lee, Ju-Woon [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of)], E-mail: sjwlee@kaeri.re.kr

    2009-07-15

    Nutrition bar, Ramen (ready-to-cook noodle), and two Korean traditional foods (Kimchi, fermented vegetable; Sujeonggwa, cinnamon beverage) have been developed as space foods using high-dose gamma irradiation. Addition of calcium lactate and vitamin C, a mild heating, deep-freezing, and gamma irradiation at 25 kGy were conducted to prepare Kimchi as a ready-to-eat space food. Sterilization of Space Kimchi (SK) was confirmed by a microbiological test. The hardness of the Space Kimchi was lower than the untreated Kimchi (CON), but higher than the irradiated only Kimchi. Sensory attributes of the SK were similar to CON, and maintained during preservation at 35 {sup o}C for 30 days. The optimal doses for eliminating the contaminated microbes and maintaining the qualities of the Nutrition bars, Ramen, and Sujeonggwa were determined at 15, 10 and 6 kGy, respectively. All the Korean space food were certificated for use in space flight conditions of 30 days by the Russian Institute for Biomedical Problems.

  3. Characterization of Thymol blue Radiochromic dosimeters for high dose applications

    Directory of Open Access Journals (Sweden)

    Feras M. Aldweri

    2018-03-01

    Full Text Available Thymol blue (TB solutions and Thymol blue Polyvinyl Alcohol (TB-PVA films have been introduced as Radiochromic dosimeter for high dose applications. The dosimeters were irradiated with gamma ray (60Co source from 5 to 30 kGy for film, and from 0.150 kGy to 4 kGy for solution. The optical density of unirradiated and irradiated TB solution as well as TB-PVA film dosimeters were studied in terms of absorbance at 434 nm using UV/VIS spectrophotometer. The effects of scan temperature, light pre-gamma irradiation, dose rate, relative humidity and stability of the absorbance of solutions and films after irradiation were investigated. We found the dose sensitivity of TB solution and TB-PVA film dosimeters increases significantly with increases of the absorbed dose as well as with the increases of TB dye concentrations. The useful dose range of developed TB solutions and TB-PVA films dosimeters is in the range 0.125–1 kGy and of 5–20 kGy, respectively. Keywords: Dose sensitivity, Radio-chromic dosimeter, Thymol blue, Absorbance, Concentrations

  4. Shelf-stable food through high dose irradiation

    International Nuclear Information System (INIS)

    Placek, V.; Svobodova, V.; Bartonicek, B.; Rosmus, J.; Camra, M.

    2004-01-01

    Irradiation of food with high doses (radappertization) is a way, how to prepare shelf-stable ready-to-eat food. The radappertization process requires that the food be heated at first to an internal temperature of at least 75 deg. C to inactivate autolytic enzyme, which could cause the spoilage during storage without refrigeration. In order to prevent radiation induced changes in sensory properties (off flavors, odors, undesirable color change, etc.) the food was vacuum packed and irradiated in frozen state at -30 deg. C or less to a minimum dose of 35 kGy. Such products have characteristics of fresh food prepared for eating even if they are stored for long time under tropical conditions. The wholesomeness (safety for consumption) has been confirmed during 40 years of testing. Within the NRI Rez 10 kinds of shelf-stable meat products have been prepared. The meat was cooked, vacuum packed in SiO x -containing pouch, freezed in liquid nitrogen and irradiated with electron beam accelerator. The microbial, chemical, and organoleptic properties have been tested

  5. Ion exchange resins as high-dose radiation dosimeters

    International Nuclear Information System (INIS)

    Alian, A.; Dessouki, A.; El-Assay, N.B.

    1984-01-01

    This paper reports on the possibility of using various types of ion exchange resins as high-dose radiation dosimeters, by analysis of the decrease in exchange capacity with absorbed dose. The resins studied are Sojuzchim-export-Moscow Cation Exchanger KU-2 and Anion Exchanger AV-17 and Merck Cation Exchanger I, and Merck Anion Exchangers II and III. Over the dose range 1 to 100 kGy, the systems show linearity between log absorbed dose and decrease in resin ion exchange capacity. The slope of this response function differs for the different resins, depending on their ionic form and degree of cross-linking. The radiation sensitivity increases in the order KU-2; Exchanger I; AV-17; Exchanger II; Exchanger III. Merck resins with moisture content of 21% showed considerably higher radiation sensitivity than those with 2 to 3% moisture content. The mechanism of radiation-induced denaturing of the ion exchanger resins involves cleavage and decomposition of functional substituents, with crosslinking playing a stabilizing role, with water and its radiolytic products serving to inhibit radical recombination and interfering with the protection cage effect of crosslinking. (author)

  6. High dose rate brachytherapy for the palliation of malignant dysphagia

    International Nuclear Information System (INIS)

    Homs, Marjolein Y.V.; Eijkenboom, Wilhelmina M.H.; Coen, Veronique L.M.A.; Haringsma, Jelle; Blankenstein, Mark van; Kuipers, Ernst J.; Siersema, Peter D.

    2003-01-01

    Background and purpose: High dose rate (HDR) brachytherapy is a commonly used palliative treatment for esophageal carcinoma. We evaluated the outcome of HDR brachytherapy in patients with malignant dysphagia. Material and methods: A retrospective analysis over a 10-year period was performed of 149 patients treated with HDR brachytherapy, administered in one or two sessions, at a median dose of 15 Gy. Patients were evaluated for functional outcome, complications, recurrent dysphagia, and survival. Results: At 6 weeks after HDR brachytherapy, dysphagia scores had improved from a median of 3 to 2 (n=104; P<0.001), however, dysphagia had not improved in 51 (49%) patients. Procedure-related complications occurred in seven (5%) patients. Late complications, including fistula formation or bleeding, occurred in 11 (7%) patients. Twelve (8%) patients experienced minor retrosternal pain. Median survival of the patients was 160 days with a 1-year survival rate of 15%. Procedure-related mortality was 2%. At follow-up, 55 (37%) patients experienced recurrent dysphagia. In 34 (23%) patients a metal stent was placed to relieve persistent or recurrent dysphagia. Conclusion: HDR brachytherapy is a moderately effective treatment for the palliation of malignant dysphagia. The incidence of early major complications is low, however, persistent and recurrent dysphagia occur frequently, and require often additional treatment

  7. High dose tetrabromobisphenol A impairs hippocampal neurogenesis and memory retention.

    Science.gov (United States)

    Kim, Ah Hyun; Chun, Hye Jeong; Lee, Seulah; Kim, Hyung Sik; Lee, Jaewon

    2017-08-01

    Tetrabromobisphenol A (TBBPA) is a brominated flame retardant that is commonly used in commercial and household products, such as, computers, televisions, mobile phones, and electronic boards. TBBPA can accumulate in human body fluids, and it has been reported that TBBPA possesses endocrine disruptive activity. However, the neurotoxic effect of TBBPA on hippocampal neurogenesis has not yet been investigated. Accordingly, the present study was undertaken to evaluate the effect of TBBPA on adult hippocampal neurogenesis and cognitive function. Male C57BL/6 mice were orally administrated vehicle or TBBPA (20 mg/kg, 100 mg/kg, or 500 mg/kg daily) for two weeks. TBBPA was observed to significantly and dose-dependently reduce the survival of newly generated cells in the hippocampus but not to affect the proliferation of newly generated cells. Numbers of hippocampal BrdU and NeuN positive cells were dose-dependently reduced by TBBPA, indicating impaired neurogenesis in the hippocampus. Interestingly, glial activation without neuronal death was observed in hippocampi exposed to TBBPA. Furthermore, memory retention was found to be adversely affected by TBBPA exposure by a mechanism involving suppression of the BDNF-CREB signaling pathway. The study suggests high dose TBBPA disrupts hippocampal neurogenesis and induces associated memory deficits. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Dimethyl sulfoxyde diethyl fumarate solution for high dose dosimetry

    International Nuclear Information System (INIS)

    Al-Kassiri, H.; Kattan, M.; Daher, Y.

    2007-06-01

    Dosimetric characterization of diethyl fumarate DEF in dimethyl sulfoxyde DMSO solution has been studied spectrophotometrically for possible application at high dose radiation dosimetry in the range (0-225 kGy). The absorption spectra of irradiated solution showed broad absorption bands between (325-400 nm) with a shoulder at 332 nm. The absorption increases as the dose is increased. Absorbance at 332 nm were measured and plotted against absorbed dose. Linear relationship and good response were found between absorbed dose and absorbance of 20% DEF concentration in the range (0-225 kGy) at the wave length, and linearity up to 250 kGy of absorbance at 332 nm .Good dose rate independence was observed in the range (14-33 kGy/h). The effect of post irradiation storage in darkness and indirect daylight conditions were not found to influence the absorption up to 700 h after irradiation. The effect of irradiation temperature within the range (0 to 60 centigrade degree) on the dosimetry performance was discussed.(author)

  9. Radiation Parameters of High Dose Rate Iridium -192 Sources

    Science.gov (United States)

    Podgorsak, Matthew B.

    A lack of physical data for high dose rate (HDR) Ir-192 sources has necessitated the use of basic radiation parameters measured with low dose rate (LDR) Ir-192 seeds and ribbons in HDR dosimetry calculations. A rigorous examination of the radiation parameters of several HDR Ir-192 sources has shown that this extension of physical data from LDR to HDR Ir-192 may be inaccurate. Uncertainty in any of the basic radiation parameters used in dosimetry calculations compromises the accuracy of the calculated dose distribution and the subsequent dose delivery. Dose errors of up to 0.3%, 6%, and 2% can result from the use of currently accepted values for the half-life, exposure rate constant, and dose buildup effect, respectively. Since an accuracy of 5% in the delivered dose is essential to prevent severe complications or tumor regrowth, the use of basic physical constants with uncertainties approaching 6% is unacceptable. A systematic evaluation of the pertinent radiation parameters contributes to a reduction in the overall uncertainty in HDR Ir-192 dose delivery. Moreover, the results of the studies described in this thesis contribute significantly to the establishment of standardized numerical values to be used in HDR Ir-192 dosimetry calculations.

  10. High-dose processing and application to Korean space foods

    Science.gov (United States)

    Song, Beom-Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Kang, Sang-Wook; Choi, Gi-Hyuk; Lee, Ju-Woon

    2009-07-01

    Nutrition bar, Ramen (ready-to-cook noodle), and two Korean traditional foods ( Kimchi, fermented vegetable; Sujeonggwa, cinnamon beverage) have been developed as space foods using high-dose gamma irradiation. Addition of calcium lactate and vitamin C, a mild heating, deep-freezing, and gamma irradiation at 25 kGy were conducted to prepare Kimchi as a ready-to-eat space food. Sterilization of Space Kimchi (SK) was confirmed by a microbiological test. The hardness of the Space Kimchi was lower than the untreated Kimchi (CON), but higher than the irradiated only Kimchi. Sensory attributes of the SK were similar to CON, and maintained during preservation at 35 °C for 30 days. The optimal doses for eliminating the contaminated microbes and maintaining the qualities of the Nutrition bars, Ramen, and Sujeonggwa were determined at 15, 10 and 6 kGy, respectively. All the Korean space food were certificated for use in space flight conditions of 30 days by the Russian Institute for Biomedical Problems.

  11. Colon mucosal cells after high-dose fractional irradiation

    International Nuclear Information System (INIS)

    Zorc-Pleskovic, R.; Vraspir-Porenta, O.; Petrovic, D.; Zorc, M.; Pleskovic, L.

    2000-01-01

    The aim of this study was to investigate histological and stereological changes in cryptal enterocytes, mucosal lymphocytes and mast cells 10 days after irradiation. For experimental model, 24 Beagle dogs 1-2 years old were used. Twelve dogs were irradiated 20 days with 32 Gy over the whole pelvis and tail. Another 12 dogs represented a control group. For the detection of apoptosis, the TUNEL technique was used. Histological and stereological analyses were performed using a Wild sampling microscope M 1000. In the irradiated group, volume density (P < 0.01), numerical density (P < 0.05) and average volume of lymphocytes (P < 0.001) were significantly lower than in the nonirradiated group. Numerical areal density of mast cells in the irradiated group was also significantly lower (P < 0.05). Volume density (P < 0.001) and average volume of mast cells (P < 0.001) were significantly higher in the irradiated group. The results of our experiments show that irradiation causes injury and loss of lymphocytes and mast cells in the colon mucosa. Apoptosis was detected in enterocytes and lymphocytes in the irradiated group and in nonirradiated group in equal numbers (2.5 ± 0.3 vs. 2.3 ± 0.3; ns.), suggesting that 10 days after high-dose irradiation, the cell loss is not due to apoptosis. (author)

  12. Tungsten and carbon surface change under high dose plasma exposure

    International Nuclear Information System (INIS)

    Martynenko, Y.V.; Khripunov, B.I.; Petrov, V.B.

    2009-01-01

    Study of surface composition dynamics has been made on the LENTA linear plasma simulator. Experiments have been made on tungsten and carbon materials subjected to steady-state plasma exposure. The achieved ion doses on the surface were 10 21 ion cm -2 . WL 10 tungsten containing 1% of La2O3 oxide and titanium-doped graphite RG-T were studied. The following experimental conditions were varied in these experiments: energy of ions, surface temperature, working gas. Irradiations of tungsten WL 10 were executed in deuterium plasma at low ion energies (about 20 eV) and at 200 eV for temperatures below 340 K. Graphite RG-T was exposed at 1300 K. Elevated surface temperature (about 1050K) was also characteristic of experiments on tungsten sample under nitrogen plasma impact (simulated inter-ELMs condition). Surface microstructure modification has been observed and surface composition changes were found on the materials showing influence of high dose plasma irradiations on element redistribution in the near surface layers. (author)

  13. High dose progesterone effects the growth of early chick embryo

    International Nuclear Information System (INIS)

    Iqbal, I.; Qamar, K.

    2014-01-01

    Objective: To find out the effect of high dose progesterone on the development of early chick embryo. Study Design: Lab based randomized controlled trial. Place and Duration of study: This study was carried out in Army Medical College and Post Graduate Institute of Poultry Sciences, Rawalpindi from June 2010 - December 2010. Material and Methods: Forty five specific pathogen free, fertile, eggs of Fyoumi species of chick were selected at zero hour of incubation. They were incubated at 37.5oC and 75% relative humidity for 26 hrs until the embryos reached stage 8 of the development. Then on stage 8 the eggs were divided into three groups consisting of 15 eggs per group. The first group (GI) was incubated without any operation. The second (G2) and third groups (G3) were injected with two and twenty times more than physiologic does of progesterone respectively. After 48 hours of incvbation, all embryos were examined for their development under light microscopy. Results: All the embryos of G1 and G2 showed normal development according to their stage of development, while 4 out of 11 embryos of G3 were under developed and their survival rate was also less. Conclusion: Exogenous progesterone at levels twenty times above its physiologic range effects the development of chick embryos. Further studies are needed to explain the mechanisms of this effect. (author)

  14. Calibration of high-dose radiation facilities (Handbook)

    International Nuclear Information System (INIS)

    Gupta, B.L.; Bhat, R.M.

    1986-01-01

    In India at present several high intensity radiation sources are used. There are 135 teletheraphy machines and 65 high intensity cobalt-60 sources in the form of gamma chambers (2.5 Ci) and PANBIT (50 Ci). Several food irradiation facilities and a medical sterilization plant ISOMED are also in operation. The application of these high intensity sources involve a wide variation of dose from 10 Gy to 100 kGy. Accurate and reproducible radiation dosimetry is essential in the use of these sources. This handbook is especially compiled for calibration of high-dose radiation facilities. The first few chapters discuss such topics as interaction of radiation with matter, radiation chemistry, radiation processing, commonly used high intensity radiation sources and their special features, radiation units and dosimetry principles. In the chapters which follow, chemical dosimeters are discussed in detail. This discussion covers Fricke dosimeter, FBX dosimeter, ceric sulphate dosimeter, free radical dosimetry, coloured indicators for irrdiation verification. A final chapter is devoted to practical hints to be followed in calibration work. (author)

  15. High-dose processing and application to Korean space foods

    International Nuclear Information System (INIS)

    Song, Beom-Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Kang, Sang-Wook; Choi, Gi-Hyuk; Lee, Ju-Woon

    2009-01-01

    Nutrition bar, Ramen (ready-to-cook noodle), and two Korean traditional foods (Kimchi, fermented vegetable; Sujeonggwa, cinnamon beverage) have been developed as space foods using high-dose gamma irradiation. Addition of calcium lactate and vitamin C, a mild heating, deep-freezing, and gamma irradiation at 25 kGy were conducted to prepare Kimchi as a ready-to-eat space food. Sterilization of Space Kimchi (SK) was confirmed by a microbiological test. The hardness of the Space Kimchi was lower than the untreated Kimchi (CON), but higher than the irradiated only Kimchi. Sensory attributes of the SK were similar to CON, and maintained during preservation at 35 o C for 30 days. The optimal doses for eliminating the contaminated microbes and maintaining the qualities of the Nutrition bars, Ramen, and Sujeonggwa were determined at 15, 10 and 6 kGy, respectively. All the Korean space food were certificated for use in space flight conditions of 30 days by the Russian Institute for Biomedical Problems.

  16. chemotherapy patients

    Directory of Open Access Journals (Sweden)

    Katarzyna Augustyniuk

    2016-02-01

    Full Text Available Background . Complementary and alternative medicine (CAM practices for cancer have become popular among oncology patients. An increasing interest in alternative medicine can be explained by the inefficiency of conventional treatment, dissatisfaction with treating patients like objects, and the will to use all available treatment methods. Objectives . The authors assessed how often patients use CAM methods, and which of them are most popular. Material and methods . The study was conducted in Military Hospital no. 109 and the Independent Public Clinical Hospital no. 1 in Szczecin among 100 chemotherapy patients. This survey-based study was performed using an original questionnaire. Results. Most respondents (68% did not use alternative methods to fight the disease. The most popular treatment methods were: herbal medicine (50%, alternative medicine preparations (38% and diet (25%, and the least common: hypnosis (3% and aromatherapy (3%. Analyzed sociodemographic factors had no effects on a choice of a CAM method. Patients obtained information about CAM methods mainly from the Internet (40%, medical staff (37% and literature (31%. Conclusions . 1. Using CAM by patients receiving chemotherapy for neoplasms is quite a common phenomenon. 2. CAM were more often chosen by women. Neither the duration of the disease nor sociodemographic data had effects on making the decision to use CAM methods. 3. The most popular CAM were: herbal medicine, alternative medicine preparations, and diet. 4. Cancer patients should receive special support from nurses and doctors as well as other members of the therapeutic team. Oncology patients should never be left on their own so that they were forced to seek help and support in therapies unconfirmed by scientific investigation.

  17. Esophageal Toxicity From High-Dose, Single-Fraction Paraspinal Stereotactic Radiosurgery

    International Nuclear Information System (INIS)

    Cox, Brett W.; Jackson, Andrew; Hunt, Margie; Bilsky, Mark; Yamada, Yoshiya

    2012-01-01

    Purpose: To report the esophageal toxicity from single-fraction paraspinal stereotactic radiosurgery (SRS) and identify dosimetric and clinical risk factors for toxicity. Methods and Materials: A total of 204 spinal metastases abutting the esophagus (182 patients) were treated with high-dose single-fraction SRS during 2003-2010. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Dose-volume histograms were combined to generate a comprehensive atlas of complication incidence that identifies risk factors for toxicity. Correlation of dose-volume factors with esophageal toxicity was assessed using Fisher’s exact test and logistic regression. Clinical factors were correlated with toxicity. Results: The median dose to the planning treatment volume was 24 Gy. Median follow-up was 12 months (range, 3-81). There were 31 (15%) acute and 24 (12%) late esophageal toxicities. The rate of grade ≥3 acute or late toxicity was 6.8% (14 patients). Fisher’s exact test resulted in significant median splits for grade ≥3 toxicity at V12 = 3.78 cm 3 (relative risk [RR] 3.7, P=.05), V15 = 1.87 cm 3 (RR 13, P=.0013), V20 = 0.11 cm 3 (RR 6, P=0.01), and V22 = 0.0 cm 3 (RR 13, P=.0013). The median split for D2.5 cm 3 (14.02 Gy) was also a significant predictor of toxicity (RR 6; P=.01). A highly significant logistic regression model was generated on the basis of D2.5 cm 3 . One hundred percent (n = 7) of grade ≥4 toxicities were associated with radiation recall reactions after doxorubicin or gemcitabine chemotherapy or iatrogenic manipulation of the irradiated esophagus. Conclusions: High-dose, single-fraction paraspinal SRS has a low rate of grade ≥3 esophageal toxicity. Severe esophageal toxicity is minimized with careful attention to esophageal doses during treatment planning. Iatrogenic manipulation of the irradiated esophagus and systemic agents classically associated with radiation recall reactions are

  18. High-dose myeloablative versus conventional low-dose radioimmunotherapy (RIT) of mantle cell lymphoma (MCL) with the chimeric anti-CD20 antibody C2B8

    International Nuclear Information System (INIS)

    Behr, T.M.; Gotthardt, M.; Schipperm, M.L.; Gratz, S.; Behe, M.P.; Brittinger, G.; Woermann, B.; Becker, W.

    2002-01-01

    CD20 has been used as target molecule for low-dose as well as high-dose, myeloablative RIT of B-cell NHL. MCL is an especially aggressive, prognostically unfavorable form of B-cell NHL. The aim of this study was to investigate whether high-dose, myeloablative RIT with the 131 I-labeled chimeric anti-CD20 antibody C2B8 (rituxan, Mabthera, Roche) may be therapeutically more effective than conventional low-dose therapy in MCL. A total of twelve patients with chemorefractory or relapsed mantle cell lymphoma were studied so far (all of them having relapsed after high-dose chemotherapy, seven of them combined with 12 Gy TBI). A diagnostic-dosimetric study was performed with 10 mCi of 131 I-C2B8 at a protein dose of 2.5 mg/kg. In case of splenic pooling, the protein dose was increased until a more 'favorable' biodistribution was obtained. Therapy was performed with conventional (30-75 mCi; n=4) or myeloablative activities (261-515 mCi; n=8) of 131 I-C2B8 at the previously optimized protein dose, aiming at whole-body doses of ≤ 0.8 Gy (for low-dose RIT) or lung doses of ≤ 27 Gy (for high-dose RIT). Clinical follow-up was obtained for up to 42 months. Overall, in 11 patients the 2.5 mg/kg protein dose was used, whereas in one patient with marked splenomegaly, 10 mg/kg were necessary to overcome the splenic antigenic sink. In the high-dose patients, non-hematologic toxicity was restricted to mild to moderate nausea, fever, transient bilirubin or liver enzyme elevations. Despite thyroid blocking, 6/8 high-dose (in contrast to 0/4 low-dose) patients developed hypothyroidism, requiring thyroxine substitution at 6-18 months after RIT. The response rate in the low-dose arm was only 1(PR)/4, whereas 7/8 high-dose patients experienced complete and the remainder a partial remission. 6 high-dose patients are still in CR (one of them relapsed locally at 3 months, one systemically at 26 months after RIT), and 7 are still alive for up to 42+ months. In contrast to low-dose therapy

  19. Physics and quality assurance for high dose rate brachytherapy

    International Nuclear Information System (INIS)

    Anderson, Lowell L.

    1995-01-01

    Purpose: To review the physical aspects of high dose rate (HDR) brachytherapy, including commissioning and quality assurance, source calibration and dose distribution measurements, and treatment planning methods. Following the introduction of afterloading in brachytherapy, development efforts to make it 'remote' culminated in 1964 with the near-simultaneous appearance of remote afterloaders in five major medical centers. Four of these machines were 'high dose rate', three employing 60Co and one (the GammaMed) using a single, cable-mounted 192Ir source. Stepping-motor source control was added to the GammaMed in 1974, making it the precursor of modern remote afterloaders, which are now suitable for interstitial as well as intracavitary brachytherapy by virtue of small source-diameter and indexer-accessed multiple channels. Because the 192Ir sources currently used in HDR remote afterloaders are supplied at a nominal air-kerma strength of 11.4 cGy cm2 s-1 (10 Ci), are not collimated in clinical use, and emit a significant fraction (15%) of photons at energies greater than 600 keV, shielding and facility design must be undertaken as carefully and thoroughly as for external beam installations. Licensing requirements of regulatory agencies must be met with respect both to maximum permissible dose limits and to the existence and functionality of safety devices (door interlocks, radiation monitors, etc.). Commissioning and quality assurance procedures that must be documented for HDR remote afterloading relate to (1) machine, applicator, guide-tube, and facility functionality checks, (2) source calibration, (3) emergency response readiness, (4) planning software evaluation, and (5) independent checks of clinical dose calculations. Source calibration checks must be performed locally, either by in-air measurement of air kerma strength or with a well ionization chamber calibrated (by an accredited standards laboratory) against an in-air measurement of air kerma strength for the

  20. Investigation of polymer composite for high dose dosimetry

    International Nuclear Information System (INIS)

    Pereira, E.L.M.; Batista, A.S.M.; Ribeiro, F.A.S.; Santos, A.P.; Faria, L.O.; Oliveira, A.H.

    2017-01-01

    Introduction: This paper presents the efficacy evaluation of PVDF and nanocomposites of the PVDF films for high gamma dosimetry. Our scope in this first part of our studies is the selection of the most promising film for future dosimetry trials, where the proportionality of response of the selected material will be investigated over a large range of doses and dose rates. Methods: Was prepared nanocomposites made by mixing Poly(vinylidene fluoride) (PVDF), zirconium oxide (ZrO 2 ) and multi-walled carbon nanotubes (MWCNTs) aiming to find dosimetric properties for applications in high dose dosimetry. The samples were irradiated with a Co-60 source at constant dose rate (16.7 kGy/h), with doses ranging from 100 to 2750 kGy. The UV-Vis and FTIR spectrophotometry have been used to monitor the appearing of C=C conjugated bonds and radio-oxidation of carbon (C=O). Results: FTIR spectrometry has that the absorbance intensities at 1715 cm -1 and 1730 cm -1 can be used for high dosimetry purposes for gamma doses ranging from 400 to 2750 kGy. In this range, it is possible to observe a linear relationship between Abs & Dose. Fading of signal was evaluated for one month and reproducibility in 2000 kGy dose. Conclusion: FTIR spectroscopic data revealed two optical absorption bands at 1715 cm -1 and 1730 cm -1 whose intensities are unambiguously related to gamma delivered dose ranging from 400 kGy to 2750 kGy. (author)

  1. Investigation of polymer composite for high dose dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, E.L.M.; Batista, A.S.M., E-mail: adriananuclear@yahoo.com.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Ribeiro, F.A.S.; Santos, A.P.; Faria, L.O.; Oliveira, A.H. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2017-07-01

    Introduction: This paper presents the efficacy evaluation of PVDF and nanocomposites of the PVDF films for high gamma dosimetry. Our scope in this first part of our studies is the selection of the most promising film for future dosimetry trials, where the proportionality of response of the selected material will be investigated over a large range of doses and dose rates. Methods: Was prepared nanocomposites made by mixing Poly(vinylidene fluoride) (PVDF), zirconium oxide (ZrO{sub 2}) and multi-walled carbon nanotubes (MWCNTs) aiming to find dosimetric properties for applications in high dose dosimetry. The samples were irradiated with a Co-60 source at constant dose rate (16.7 kGy/h), with doses ranging from 100 to 2750 kGy. The UV-Vis and FTIR spectrophotometry have been used to monitor the appearing of C=C conjugated bonds and radio-oxidation of carbon (C=O). Results: FTIR spectrometry has that the absorbance intensities at 1715 cm{sup -1} and 1730 cm{sup -1} can be used for high dosimetry purposes for gamma doses ranging from 400 to 2750 kGy. In this range, it is possible to observe a linear relationship between Abs & Dose. Fading of signal was evaluated for one month and reproducibility in 2000 kGy dose. Conclusion: FTIR spectroscopic data revealed two optical absorption bands at 1715 cm{sup -1} and 1730 cm{sup -1} whose intensities are unambiguously related to gamma delivered dose ranging from 400 kGy to 2750 kGy. (author)

  2. Urethral stricture following high dose rate brachytherapy for prostate cancer

    International Nuclear Information System (INIS)

    Sullivan, Lisa; Williams, Scott G.; Tai, Keen Hun; Foroudi, Farshad; Cleeve, L.; Duchesne, Gillian M.

    2009-01-01

    Purpose: To evaluate the incidence, timing, nature and outcome of urethral strictures following high dose rate brachytherapy (HDRB) for prostate carcinoma. Methods and materials: Data from 474 patients with clinically localised prostate cancer treated with HDRB were analysed. Ninety percent received HDRB as a boost to external beam radiotherapy (HDRBB) and the remainder as monotherapy (HDRBM). Urethral strictures were graded according to the Common Terminology Criteria for Adverse Events v3.0. Results: At a median follow-up of 41 months, 38 patients (8%) were diagnosed with a urethral stricture (6-year actuarial risk 12%). Stricture location was bulbo-membranous (BM) urethra in 92.1%. The overall actuarial rate of grade 2 or more BM urethral stricture was estimated at 10.8% (95% CI 7.0-14.9%), with a median time to diagnosis of 22 months (range 10-68 months). All strictures were initially managed with either dilatation (n = 15) or optical urethrotomy (n = 20). Second line therapy was required in 17 cases (49%), third line in three cases (9%) and 1 patient open urethroplasty (grade 3 toxicity). Predictive factors on multivariate analysis were prior trans-urethral resection of prostate (hazard ratio (HR) 2.81, 95% CI 1.15-6.85, p = 0.023); hypertension (HR 2.83, 95% CI 1.37-5.85, p = 0.005); and dose per fraction used in HDR (HR for 1 Gy increase per fraction 1.33, 95% CI 1.08-1.64, p = 0.008). Conclusions: BM urethral strictures are the most common late grade 2 or more urinary toxicity following HDR brachytherapy for prostate cancer. Most are manageable with minimally invasive procedures. Both clinical and dosimetric factors appear to influence the risk of stricture formation.

  3. Tolerance of the Brachial Plexus to High-Dose Reirradiation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Allen M., E-mail: achen5@kumc.edu; Yoshizaki, Taeko; Velez, Maria A.; Mikaeilian, Argin G.; Hsu, Sophia; Cao, Minsong

    2017-05-01

    Purpose: To study the tolerance of the brachial plexus to high doses of radiation exceeding historically accepted limits by analyzing human subjects treated with reirradiation for recurrent tumors of the head and neck. Methods and Materials: Data from 43 patients who were confirmed to have received overlapping dose to the brachial plexus after review of radiation treatment plans from the initial and reirradiation courses were used to model the tolerance of this normal tissue structure. A standardized instrument for symptoms of neuropathy believed to be related to brachial plexus injury was utilized to screen for toxicity. Cumulative dose was calculated by fusing the initial dose distributions onto the reirradiation plan, thereby creating a composite plan via deformable image registration. The median elapsed time from the initial course of radiation therapy to reirradiation was 24 months (range, 3-144 months). Results: The dominant complaints among patients with symptoms were ipsilateral pain (54%), numbness/tingling (31%), and motor weakness and/or difficulty with manual dexterity (15%). The cumulative maximum dose (Dmax) received by the brachial plexus ranged from 60.5 Gy to 150.1 Gy (median, 95.0 Gy). The cumulative mean (Dmean) dose ranged from 20.2 Gy to 111.5 Gy (median, 63.8 Gy). The 1-year freedom from brachial plexus–related neuropathy was 67% and 86% for subjects with a cumulative Dmax greater than and less than 95.0 Gy, respectively (P=.05). The 1-year complication-free rate was 66% and 87%, for those reirradiated within and after 2 years from the initial course, respectively (P=.06). Conclusion: The development of brachial plexus–related symptoms was less than expected owing to repair kinetics and to the relatively short survival of the subject population. Time-dose factors were demonstrated to be predictive of complications.

  4. Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure.

    Science.gov (United States)

    Teinturier, C; Hartmann, O; Valteau-Couanet, D; Benhamou, E; Bougneres, P F

    1998-11-01

    We studied pubertal status and ovarian function in 21 girls aged 11-21 years who had earlier received 1.2-13 years (median 7 years) high-dose chemotherapy and autologous BMT without TBI for malignant tumors. Ten of them were given busulfan (600 mg/m2) and melphalan (140 mg/m2) with or without cyclophosphamide (3.6 g/m2). Eleven others did not receive busulfan. Twelve girls (57%) had clinical and hormonal evidence of ovarian failure. Among nine others who had completed normal puberty, six had normal gonadotropin levels, one had elevated gonadotropin levels and two had gonadotropin levels at the upper limit of normal. The 10 girls who received busulfan all developed severe and persistent ovarian failure. High-dose busulfan is therefore a major cause of ovarian failure even when given in the prepubertal period. These findings emphasize the need for long-term endocrine follow-up of these patients in order to initiate estrogen replacement therapy.

  5. High dose rate brachytherapy in treatment of high grade astrocytomas

    International Nuclear Information System (INIS)

    Garcia-Alejo, R.; Delgado, J.M.; Cerro, E. del; Torres, J.J.; Martinez, R.

    1996-01-01

    From May 1994 to June 1995, 18 patients with high grade astrocytomas were entered prospectively on a selective protocol combining surgery, external beam radiotherapy, stereotactic interstitial implantation with HDR Iridium 192 and chemotherapy. Only those patients with tumor size 100cc or less average dimension, high grade astrocytoma, Karnofsky 70 or greater, unilateral, circumscribed, unifocal, tumor stable or responding to external radiation and supratentorial were included in the study. Ages ranged from 16 to 69 years. There were 13 males and 5 females. Surgery consisted of biopsy only in 3 patients, subtotal resection in 11, and gross total resection in 4 patients. Focal external beam radiation portals included the contrast enhancing mass on CT scan plus a 3 cm margin. The protocol called for minimum tumor dose of 60 Gy to be given in 2 Gy daily fractions. An interstitial brachytherapy boost was to be performed two weeks after the conclusion of external beam radiation. The dose was 30 Gy in 4 fractions. The authors analyze on basis on their personal experience, the possibilities and the limits offered by this therapeutic procedure in neuro-oncology. Using stereotactic techniques, interstitial brachytherapy of brain tumors was technically possible with negligible acute morbidity and mortality, and appeared to be effective and may provide for an increase in tumor control in selected cases

  6. 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

    Energy Technology Data Exchange (ETDEWEB)

    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 [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Chen, Yue, E-mail: chenyue5523@126.com [Department of Nuclear Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Wu, Jing-Bo, E-mail: wjb6147@163.com [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China)

    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.

  7. Malaria chemotherapy.

    Science.gov (United States)

    Winstanley, Peter; Ward, Stephen

    2006-01-01

    Most malaria control strategies today depend on safe and effective drugs, as they have done for decades. But sensitivity to chloroquine, hitherto the workhorse of malaria chemotherapy, has rapidly declined throughout the tropics since the 1980s, and this drug is now useless in many high-transmission areas. New options for resource-constrained governments are few, and there is growing evidence that the burden from malaria has been increasing, as has malaria mortality in Africa. In this chapter, we have tried to outline the main pharmacological properties of current drugs, and their therapeutic uses and limitations. We have summarised the ways in which these drugs are employed, both in the formal health sector and in self-medication. We have briefly touched on the limitations of current drug development, but have tried to pick out a few promising drugs that are under development. Given that Plasmodium falciparum is the organism that kills, and that has developed multi-drug resistance, we have tended to focus upon it. Similarly, given that around 90% of global mortality from malaria occurs in Africa, there is the tendency to dwell on this continent. We give no apology for placing our emphasis upon the use of antimalarial drugs in endemic populations rather than their use for prophylaxis in travellers.

  8. Chemotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Pfister, David G.

    1997-01-01

    Purpose/Objective: The role of chemotherapy in the management of squamous cell carcinoma of the upper aerodigestive tract is undergoing rapid evolution. Historically, the use of chemotherapy was limited to patients with incurable disease who had exhausted all surgical and radiation therapy options. The results of recent randomized trials, however, suggest an increasing role for chemotherapy as part of primary management in patients with unresectable disease; advanced larynx or hypopharynx cancer with the intent of larynx preservation, or advanced nasopharynx cancer. This refresher course will provide a comprehensive overview of the current indications for chemotherapy in the management of these malignancies, and will highlight areas of controversy and future directions of investigation. More specifically, the following areas will be emphasized. 1. The identification of drugs commonly used in the management of head and neck cancer, their customary dosing and side effects. 2. The impact of induction and/or adjuvant chemotherapy combined with surgery and radiation therapy as defined by randomized trials, including a discussion of the Head and Neck Contracts program and the Intergroup adjuvant trial. 3. The development of larynx/function preservation treatment programs, including a review of the Veterans Administration and EORTC larynx preservation studies. 4. The evolving role of chemotherapy as part of innovative combined modality programs, especially in patients with unresectable disease. The rationale and utility of sequential versus concomitant/alternating chemotherapy-radiation strategies, and relevant randomized clinical trials comparing the different strategies will be discussed. 5. The appropriate application of chemotherapy in the palliative setting, including a discussion of the relative merits of single-agent versus combination chemotherapy

  9. Chemotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Pfister, David G.

    1995-01-01

    Purpose/Objective: The role of chemotherapy in the management of squamous cell carcinoma of the upper aerodigestive tract is undergoing rapid evolution. Historically, the use of chemotherapy was limited to patients with incurable disease who had exhausted all surgical and radiation therapy options. The results of recent randomized trials, however, suggest an increasing role for chemotherapy as part of primary management in patients seeking to avoid potentially morbid surgical procedures or with unresectable disease. This refresher course will provide a comprehensive overview of the current indications for chemotherapy in the management of these malignancies, and will highlight areas of controversy and future directions of investigation. More specifically, the following areas will be emphasized. 1. The identification of drugs commonly used in the management of head and neck cancer, their customary dosing and side effects. 2. The impact of induction and/or adjuvant chemotherapy combined with surgery and radiation therapy as defined by randomized trials, including a discussion of the Head and Neck Contracts program and the Intergroup adjuvant trial. 3. The development of larynx/function preservation treatment programs, including a review of the Memorial Hospital experience with larynx preservation and the Veterans Administration larynx preservation study. 4. The evolving role of chemotherapy as part of innovative combined modality programs, especially in patients with unresectable disease. The rationale and utility of sequential versus concomitant/alternating chemotherapy-radiation strategies, and relevant randomized clinical trials comparing the different strategies will be discussed. 5. The appropriate application of chemotherapy in the palliative setting, including a discussion of the relative merits of single-agent versus combination chemotherapy

  10. Local vaginal anesthesia during high-dose-rate intracavitary brachytherapy for cervical cancer

    International Nuclear Information System (INIS)

    Chen, H.-C.; Wan Leung, Stephen; Wang, C.-J.; Sun, L.-M.; Fang, F.-M.; Huang, E.-Y.; Wang, S.-J.; Yang, C.-W.

    1998-01-01

    Purpose: To evaluate the clinical efficacy of local vaginal lidocaine application for pain relief during high-dose-rate (HDR) intracavitary brachytherapy for patients with cervical cancer, and to investigate sequential changes in serum levels of lidocaine during the procedures. Methods and Materials: This prospective study was designed to examine the analgesic effect, physical response, and side effects of local anesthesia during HDR intracavitary brachytherapy. Forty patients were enrolled. All patients received 10-15 MV X-rays to the pelvis with a total dose of 45-59.4 Gy 5-6 weeks before undergoing HDR intracavitary brachytherapy. All patients underwent first intracavitary brachytherapy under general anesthesia. These patients were randomly allocated to receive one of two different treatment protocols as follows: (1) treatment session - control session - treatment session - control session; or (2) control session - treatment session- control session - treatment session. In the treatment sessions, topical anesthesia was administered using 4 ml of 10% lidocaine solution sprayed liberally on the cervix and vagina during intracavitary brachytherapy. In the control sessions, a placebo was administered in the same manner during brachytherapy. The Hensche's applicators for brachytherapy were inserted into the cervix and vagina 5 min after lidocaine application. The visual analogue scale (VAS) was used to assess pain and discomfort during brachytherapy. Blood pressure and heart rates were measured to evaluate the physiological response. Another prospective study was then performed to investigate the sequential changes of serum lidocaine levels during the anesthetic procedure. Eleven additional patients with similar disease state and demographic characteristics were enrolled and blood samples were obtained before, and 5, 15, 30, and 45 min after the initiation of lidocaine application. Results: The mean VAS values recorded during the treatment sessions and control

  11. Interaction of 2-Gy Equivalent Dose and Margin Status in Perioperative High-Dose-Rate Brachytherapy

    International Nuclear Information System (INIS)

    Martinez-Monge, Rafael; Cambeiro, Mauricio; Moreno, Marta; Gaztanaga, Miren; San Julian, Mikel; Alcalde, Juan; Jurado, Matias

    2011-01-01

    Purpose: To determine patient, tumor, and treatment factors predictive of local control (LC) in a series of patients treated with either perioperative high-dose-rate brachytherapy (PHDRB) alone (Group 1) or with PHDRB combined with external-beam radiotherapy (EBRT) (Group 2). Patient and Methods: Patients (n = 312) enrolled in several PHDRB prospective Phase I-II studies conducted at the Clinica Universidad de Navarra were analyzed. Treatment with PHDRB alone, mainly because of prior irradiation, was used in 126 patients to total doses of 32 Gy/8 b.i.d. or 40 Gy/10 b.i.d. treatments after R0 or R1 resections. Treatment with PHDRB plus EBRT was used in 186 patients to total doses of 16 Gy/4 b.i.d. or 24 Gy/6 b.i.d. treatments after R0 or R1 resections along with 45 Gy of EBRT with or without concomitant chemotherapy. Results: No dose-margin interaction was observed in Group 1 patients. In Group 2 patients there was a significant interaction between margin status and 2-Gy equivalent (Eq2Gy) dose (p = 0.002): (1) patients with negative margins had 9-year LC of 95.7% at Eq2Gy = 62.9Gy; (2) patients with close margins of >1 mm had 9-year LC of 92.4% at Eq2Gy = 72.2Gy, and (3) patients with positive/close <1-mm margins had 9-year LC of 68.0% at Eq2Gy = 72.2Gy. Conclusions: Two-gray equivalent doses ≥70 Gy may compensate the effect of close margins ≥1 mm but do not counterbalance the detrimental effect of unfavorable (positive/close <1 mm) resection margins. No dose-margin interaction is observed in patients treated at lower Eq2Gy doses ≤50 Gy with PHDRB alone.

  12. High-Dose Lanreotide in the Treatment of Poorly Differentiated Pancreatic Neuroendocrine Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Frank Van Fraeyenhove

    2014-03-01

    Full Text Available Pancreatic neuroendocrine tumors (NETs, including poorly differentiated carcinomas (NECs, are rarely encountered. The majority of these tumors do not secrete excess hormones, but functioning NETs produce large amounts of vasoactive peptides and may cause carcinoid syndrome. Synthetic somatostatin analogs (SSAs have been widely used in NETs for control of hormonal syndromes. Here, we present a case of poorly differentiated, grade 3 pancreatic NEC associated with carcinoid syndrome, for which adequate symptom control was achieved for 2 years and 4 months using the long-acting SSA lanreotide Autogel®. In February 2009, a 55-year-old woman presented with episodes of flushing, diarrhea and epigastric pain. Imaging techniques revealed the presence of a metabolically active mass expressing somatostatin receptors in the hilar area of the liver. Histopathological examination confirmed the malignant nature of the mass, which was identified as a poorly differentiated grade 3 pancreatic NEC (TNM staging: T4NxM0. Therapeutic options were limited for the patient because of the extent of the primary mass involving the celiac axis, severe gastrointestinal toxicity experienced as a side effect of chemotherapy with cisplatin-etoposide and, later in the course of the disease, extensive liver metastases and carcinoid heart syndrome. Along with a palliative debulking surgery and right portal vein embolization, biotherapy with a high dose of lanreotide Autogel (120 mg/14 days contributed to alleviation of symptoms caused by hormone overproduction, even after the development of liver metastases. These results suggest that patients with poorly differentiated NECs who exhibit signs of carcinoid syndrome can benefit from treatment with somatostatin analogs.

  13. Reduced time for urinary alkalinization before high-dose methotrexate with preadmission oral bicarbonate.

    Science.gov (United States)

    Kintzel, Polly E; Campbell, Alan D; Yost, Kathleen J; Brinker, Brett T; Arradaza, Nicole V; Frobish, Daniel; Wehr, Alison M; O'Rourke, Timothy J

    2012-06-01

    Hydration and urinary alkalinization are essential for reducing renal dysfunction with high dose methotrexate (HDMTX). This report presents an analysis of institutional methods used to achieve adequate urinary alkalinization and output for patients receiving single agent HDMTX. Renal and metabolic parameters of tolerance were examined. Medical records of adult patients receiving HDMTX during the calendar years of 2008-2009 were retrospectively reviewed to determine the time to achieve urine pH > 7. Number of hospital days, bicarbonate dose, ordered hydration rate, urine output, and urine pH were assessed. A survival analysis model was run for time to urine pH > 7 using preadmission oral bicarbonate as a predictor variable and including a frailty term. Observational statistics were performed for other parameters. The analysis included 79 encounters for ten patients. Urine pH > 7 was achieved more rapidly in patients receiving preadmission oral bicarbonate (P = 0.012). The number of patients receiving HDMTX on the same day as admission was greater for those receiving preadmission oral bicarbonate (47%) in comparison to those who did not (2%), and they spent less time in the hospital. A standard regimen for hydration and urinary alkalinization based on this project is reported. The nature and frequency of adverse events were as expected for this treatment. At our institution, the time to achieve urinary alkalinization was reduced for patients receiving preadmission oral bicarbonate which facilitated chemotherapy infusion on the same day as admission and decreased the number of calendar days that patients stayed in the hospital.

  14. Near fatal 5-FU gut toxicity post surgery--remarkable effect of high-dose sucralfate.

    Science.gov (United States)

    Toh, James Wei Tatt; Morris, David; Chen, Zhuoran; Chen, Cindy

    2015-06-01

    The objective of this review article and case report was to investigate the effectiveness of high-dose sucralfate on severe life-threatening 5-fluorouracil (5-FU) gut toxicity, with reference to, but not limited to dihydropyrimidine dehydrogenase (DPD) deficiency. A search was conducted on PubMed from 1950 to July 2013 for original studies on 5-FU gut toxicity and sucralfate. Studies were limited to human trials and English language and all articles included in this study were assessed with the application of predetermined selection criteria. Each article was then reviewed independently by two reviewers. A case report from our own centre was included in this review. From 33 results, 6 manuscripts were identified including 4 randomized controlled trial. One trial evaluated the use of sucralfate to alleviate stomatitis in patients with 5-FU-based chemotherapy. The other three trials evaluated the role of sucralfate in radiation toxicity. There was one case report which showed gastroscopy confirmed normalization of severe dysplastic erosive gastroduodenitis attributed to hepatic arterial infusion of 5-FU following a 2-month course of sucralfate and cimetidine and one case series showing clinical and sigmoidoscopically demonstrated improvement in ulcerative colitis in majority of patients receiving sucralfate enemas. There was no current literature specifically focussed on the role of sucralfate in 5-FU gut toxicity. Our case report describes the clinical course and successful treatment with sucralfate of a patient with Pseudomyxoma peritonei (PMP) who experienced 5-FU gut toxicity resulting in life-threatening bleeding due to presumed DPD deficiency post intraperitoneal 5-FU administration. This review article showed a lack of literature concerning the use of sucralfate in 5-FU gut toxicity. In our patient's case, sucralfate had a crucial role in the management of near fatal 5-FU gut toxicity, and further evaluation is required.

  15. High-dose rate intra-operative radiation therapy for local advanced and recurrent colorectal cancer

    International Nuclear Information System (INIS)

    Harrison, L.B.; Mychalczak, B.; Enker, W.; Anderson, L.; Cohen, A.E.; Minsky, B.

    1996-01-01

    In an effort to improve the local control for advanced and recurrent cancers of the rectum, we have integrated high-dose rate intra-operative radiation therapy (HDR-IORT) into the treatment program. Between 11/92 and 10/95, 47 patients (pts) were treated. There were 26 males and 21 females whose ages ranged from 30-80 (median = 62) years. There were 19 pts with primary unresectable rectal cancer, and 28 pts who were treated for recurrent rectal cancer. Histology was adenocarcinoma - 45 pts, squamous cancer - 2 pts. The range of follow-up is 1-34 months (median = 14 months). The majority of primary unresectable pts received pre-operative radiation therapy (4500-5040 cGy) with chemotherapy (5-FU with Leucovorin) 4-6 weeks later, they underwent resection + HDR-IORT (1200 cGy). For the 28 pts with recurrent cancer, the majority received surgery and HDR-IORT alone because they had received prior RT. For the pts with primary unresectable disease, actuarial 2-year local control was 77%, actuarial distant metastasis-free survival was 71%, disease free survival was 66%, and overall survival was 84%. For those pts with recurrent disease, actuarial 2-year local control rate was 65%, distant metastasis-free survival was 65%, disease free survival was 47%, and overall survival was 61%. Complications occurred in 36%. There were no cases where the anatomical distribution of disease, or technical limitations prevented the adequate delivery of HDR-IORT. We conclude that this technique was most versatile, and enabled all appropriate pts to receive IORT. The preliminary data in terms of local control are encouraging, even for the poor prognostic sub-group of pts with recurrent cancer

  16. Neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy or surgery for operable thoracic esophageal carcinoma

    International Nuclear Information System (INIS)

    Masao, Murakami; Yasumasa, Kuroda; Yosiaki, Okamoto; Koichi, Kono; Eisaku, Yoden; Fusako, Kusumi; Kiyoshi, Hajiro; Satoru, Matsusue; Hiroshi, Takeda

    1997-01-01

    Purpose: A prospective clinical trial was undertaken to investigate the feasibility of concurrent chemoradiotherapy for the esophageal carcinoma. Materials and Methods: Between June 1989 and May 1996, forty patients with operable squamous cell carcinoma of the thoracic esophagus (stage 0 to III: UICC 1987), aged 45 to 78 (mean:64), were enrolled in a study of neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy (CRT group) or surgery (CRT-S group). Neoadjuvant chemoradiotherapy consisted of 44Gy in 40 fractions for 4 weeks (2.2Gy/2Fr./day) through 10MVX rays, with one or two courses of cisplatin (80-150mg/body, mean:90mg/m 2 , day 1, bolus injection) and 5-fluorouracil (500-1500mg/body/day, mean:600mg/m 2 , day 1-4, continuous infusion). After completion of neoadjuvant chemoradiotherapy, clinical complete response (CR) was observed in 16 patients, partial response (PR) in 22, and no change (NC) in 2. Thirty responding patients (CR:16, PR:14) entered in CRT group, and 10 non-responding patients (PR:8, NC:2) followed by surgery (CRT-S group). A cumulative median dose of 66Gy for Tis,T1 and 71Gy for T2-T4 tumor with/without high-dose-rate intraluminal brachytherapy, and one to three courses of chemotherapy were delivered in CRT group. Intraoperative radiotherapy for abdominal lymphatic system and postoperative supraclavicular irradiation were added in CRT-S group. Results: Clinical CR rate at the completion of treatment showed 90% in CRT group, and pathological CR rate 10% in CRT-S group. The overall median survival was 45 months, survival at 1, 2, 3 years being 100%, 72%, 56%, respectively. Loco-regional failure was observed in 7 patients (all in CRT group), distant failure in 6 (3 in CRT group, 3 in CRT-S group) and loco-regional with distant failure in 1 (CRT group). Four patients of loco-regional recurrence in CRT group were salvaged by surgery. Overall survival at 2-, 3-years for CRT vs. CRT-S group was 72%, 64% vs. (1(1)); 100

  17. Sequential charged particle reaction

    International Nuclear Information System (INIS)

    Hori, Jun-ichi; Ochiai, Kentaro; Sato, Satoshi; Yamauchi, Michinori; Nishitani, Takeo

    2004-01-01

    The effective cross sections for producing the sequential reaction products in F82H, pure vanadium and LiF with respect to the 14.9-MeV neutron were obtained and compared with the estimation ones. Since the sequential reactions depend on the secondary charged particles behavior, the effective cross sections are corresponding to the target nuclei and the material composition. The effective cross sections were also estimated by using the EAF-libraries and compared with the experimental ones. There were large discrepancies between estimated and experimental values. Additionally, we showed the contribution of the sequential reaction on the induced activity and dose rate in the boundary region with water. From the present study, it has been clarified that the sequential reactions are of great importance to evaluate the dose rates around the surface of cooling pipe and the activated corrosion products. (author)

  18. High dose rate 192Ir calibration: Indonesia experiences

    International Nuclear Information System (INIS)

    Nasukha; Tjiptanto, D.; Darmasyah, R.; Kurniawan, B.

    2002-01-01

    Indonesia with a population of more than 200 Million people which spread on about 5000 islands, up to now only has 23 radiotherapy centers and some not active anymore. As mention by Parkin et al that Cervix/Utery and breast cancer are the most estimated numbers of new cases of cancers in women for developing countries, stomach and lung cancers in men. Indonesia as a developing country is likely similar to other developing countries on numbers of new cases of cancers in women. But quite different in men, in Indonesia the most common cancers are nasopharynx and thyroid cancers. The use of lr-192 sources in high dose-rate (HDR) remotely afterloaded brachytherapy treatments have greatly increased in recent years and variety of such sources are commercially available. Nine radiotherapy centers in Indonesia installed Nucletron microSelectron HDR remote afterloader. Based on the data of CiptoMangunkusurno Hospital, Jakarta that the most common cancers are the cervix, breast, nasopharynx and thyroid cancers which of percentage are about 31%, 25 %, 13%, and 6 % respectively. It means that the use of HDR 192 Ir brachytherapy has to be an effective tool in the treatments. Two methods have been studied and applied to calibrate HDR 192 Ir brachytherapy in Indonesia, especially for Nucletron microSelectron HDR 192 lr remote afterloader brachytherapy. Calibration of HDR 192 Ir brachytherapy source has been done by Cavity lonization Chamber and with Well Type lonization Chamber. First, 0.6 cc of NE Farmer type dosimeter that was calibrated to 60 Co and 250 kV of x-rays in air kerma was used in this experiment. Position of measurement (detector and source) at the center of the room and about 1 meter from the floor. Eight variation of distances from 10 cm to 40 cms have been carried out measurement as recommended by IAEA-TECDOC-1079. Correction have been given for scatters, non-uniformity, and attenuation. To solve the problem of scatter correction factor was used Matlab programming

  19. High-dose-rate brachytherapy in uterine cervical carcinoma

    International Nuclear Information System (INIS)

    Patel, Firuza D.; Rai, Bhavana; Mallick, Indranil; Sharma, Suresh C.

    2005-01-01

    Purpose: High-dose-rate (HDR) brachytherapy is in wide use for curative treatment of cervical cancer. The American Brachytherapy Society has recommended that the individual fraction size be <7.5 Gy and the range of fractions should be four to eight; however, many fractionation schedules, varying from institution to institution, are in use. We use 9 Gy/fraction of HDR in two to five fractions in patients with carcinoma of the uterine cervix. We found that our results and toxicity were comparable to those reported in the literature and hereby present our experience with this fractionation schedule. Methods and Materials: A total of 121 patients with Stage I-III carcinoma of the uterine cervix were treated with HDR brachytherapy between 1996 and 2000. The total number of patients analyzed was 113. The median patient age was 53 years, and the histopathologic type was squamous cell carcinoma in 93% of patients. The patients were subdivided into Groups 1 and 2. In Group 1, 18 patients with Stage Ib-IIb disease, tumor size <4 cm, and preserved cervical anatomy underwent simultaneous external beam radiotherapy to the pelvis to a dose of 40 Gy in 20 fractions within 4 weeks with central shielding and HDR brachytherapy of 9 Gy/fraction, given weekly, and interdigitated with external beam radiotherapy. The 95 patients in Group 2, who had Stage IIb-IIIb disease underwent external beam radiotherapy to the pelvis to a dose of 46 Gy in 23 fractions within 4.5 weeks followed by two sessions of HDR intracavitary brachytherapy of 9 Gy each given 1 week apart. The follow-up range was 3-7 years (median, 36.4 months). Late toxicity was graded according to the Radiation Therapy Oncology Group criteria. Results: The 5-year actuarial local control and disease-free survival rate was 74.5% and 62.0%, respectively. The actuarial local control rate at 5 years was 100% for Stage I, 80% for Stage II, and 67.2% for Stage III patients. The 5-year actuarial disease-free survival rate was 88.8% for

  20. Optimized patient-trajectory for patients undergoing treatment with high-dose chemotherapy and autologous stem cell transplantation

    DEFF Research Database (Denmark)

    Bartels, Frederik Reith; Smith, Nicholas Simon; Gørløv, Jette Sønderskov

    2015-01-01

    was reported by using a patient diary, weekly questionnaire and count of daily attendance in supervised sessions during hospital stay. Data collection was scheduled shortly after diagnosis, admission, discharge and eight weeks after discharge. Success criteria were: no severe adverse events in relation...

  1. Physical Compatibility of Micafungin With Sodium Bicarbonate Hydration Fluids Commonly Used With High-Dose Methotrexate Chemotherapy.

    Science.gov (United States)

    Joiner, Logan C; Tynes, Clay; Arnold, John; Miller, Rachel R; Gorman, Greg

    2018-04-01

    Purpose: The purpose of this study was to determine the physical compatibility of micafungin with commonly used concentrations of sodium bicarbonate hydration fluids administered via a Y-site connected to a central venous catheter (Y-site/CVC). Methods: Micafungin sodium (evaluated concentration of 1.5 mg/mL) was combined in a 3:1 (vehicle:drug) ratio with the following commonly used hydration vehicles: 40 mEq/L sodium bicarbonate in 5% dextrose in water with ¼ normal saline (40SB-D5W-1/4NS), 75 mEq/L sodium bicarbonate in D5W (75SB-D5W), and 154 mEq/L sodium bicarbonate in D5W (154SB-D5W). A 3:1 ratio was used based on the flow rates (typically 125 mL/m 2 /h for bicarbonate-containing vehicles and 50 mL/h for micafungin) of the corresponding solutions in a clinical setting. Visual observations recorded to determine physical compatibility included visual inspection against different backgrounds (unaided, black, and white). Other physical observations were as follows: odor, evolution of gas, pH, and turbidity immediately recorded after mixing and at specified time points up to 2 hours. Evaluations at each time point were compared against baseline observation values at Time 0. Results: All combinations tested were found to be compatible up to 2 hours. Time points beyond 2 hours cannot be safely verified as compatible. Conclusion: Micafungin may be administered safely using a Y-site/CVC delivery system with all the vehicles tested in this study.

  2. The Role of High Dose Interleukin-2 in the Era of Targeted Therapy.

    Science.gov (United States)

    Gills, Jessie; Parker, William P; Pate, Scott; Niu, Sida; Van Veldhuizen, Peter; Mirza, Moben; Holzbeierlein, Jeffery M; Lee, Eugene K

    2017-09-01

    We assessed survival outcomes following high dose interleukin-2 in a contemporary cohort of patients during the era of targeted agents. We retrospectively reviewed the records of patients with metastatic renal cell carcinoma treated with high dose interleukin-2 between July 2007 and September 2014. Clinicopathological data were abstracted and patient response to therapy was based on RECIST (Response Evaluation Criteria In Solid Tumors), version 1.1 criteria. The Kaplan-Meier method was used to estimate progression-free and overall survival in the entire cohort, the response to high dose interleukin-2 in regard to previous targeted agent therapy and the response to the targeted agent in relation to the response to high dose interleukin-2. We identified 92 patients, of whom 87 had documentation of a response to high dose interleukin-2. Median overall survival was 34.4 months from the initiation of high dose interleukin-2 therapy in the entire cohort. Patients who received targeted therapy before high dose interleukin-2 had overall survival (median 34.4 and 30.0 months, p = 0.88) and progression-free survival (median 1.5 and 1.7 months, p = 0.8) similar to those in patients who received no prior therapy, respectively. Additionally, patients with a complete or partial response to high dose interleukin-2 had similar outcomes for subsequent targeted agents compared to patients whose best response was stable or progressive disease (median overall survival 30.1 vs 25.4 months, p = 0.4). Our data demonstrate that patient responses to high dose interleukin-2 and to targeted agents before and after receiving high dose interleukin-2 are independent. As such, carefully selected patients should be offered high dose interleukin-2 for the possibility of a complete and durable response without the fear of limiting the treatment benefit of targeted agents. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  3. Risks Associated with High-Dose Lactobacillus rhamnosus in an Escherichia coli Model of Piglet Diarrhoea

    DEFF Research Database (Denmark)

    Li, Xiao-Qiong; Zhu, Yao-Hong; Zhang, Hong-Fu

    2012-01-01

    might be more effective than a high dose at ameliorating diarrhoea. There is a risk that high-dose L. rhamnosus pretreatment may negate the preventative effects, thus decreasing the prophylactic benefits against potential enteric pathogens. Our data suggest a safe threshold for preventative use...

  4. Split high-dose oral levothyroxine treatment as a successful therapy option in myxedema coma.

    Science.gov (United States)

    Charoensri, Suranut; Sriphrapradang, Chutintorn; Nimitphong, Hataikarn

    2017-10-01

    High-dose intravenous thyroxine (T4) is the preferable treatment for myxedema coma. We describe the clinical course of a 69-year-old man who presented with myxedema coma and received oral levothyroxine (LT4) therapy (1 mg) in a split dose. This suggests split high-dose oral LT4 as a therapeutic option in myxedema coma.

  5. Chemotherapy to Treat Cancer

    Science.gov (United States)

    Chemotherapy is a type of cancer treatment that uses drugs to kill cancer cells. Learn how chemotherapy works against cancer, why it causes side effects, and how it is used with other cancer treatments.

  6. Sequential stochastic optimization

    CERN Document Server

    Cairoli, Renzo

    1996-01-01

    Sequential Stochastic Optimization provides mathematicians and applied researchers with a well-developed framework in which stochastic optimization problems can be formulated and solved. Offering much material that is either new or has never before appeared in book form, it lucidly presents a unified theory of optimal stopping and optimal sequential control of stochastic processes. This book has been carefully organized so that little prior knowledge of the subject is assumed; its only prerequisites are a standard graduate course in probability theory and some familiarity with discrete-paramet

  7. High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study.

    Science.gov (United States)

    Appelt, Ane L; Pløen, John; Harling, Henrik; Jensen, Frank S; Jensen, Lars H; Jørgensen, Jens C R; Lindebjerg, Jan; Rafaelsen, Søren R; Jakobsen, Anders

    2015-08-01

    Abdominoperineal resection is the standard treatment for patients with distal T2 or T3 rectal cancers; however, the procedure is extensive and mutilating, and alternative treatment strategies are being investigated. We did a prospective observational trial to assess whether high-dose radiotherapy with concomitant chemotherapy followed by observation (watchful waiting) was successful for non-surgical management of low rectal cancer. Patients with primary, resectable, T2 or T3, N0-N1 adenocarcinoma in the lower 6 cm of the rectum were given chemoradiotherapy (60 Gy in 30 fractions to tumour, 50 Gy in 30 fractions to elective lymph node volumes, 5 Gy endorectal brachytherapy boost, and oral tegafur-uracil 300 mg/m(2)) every weekday for 6 weeks. Endoscopies and biopsies of the tumour were done at baseline, throughout the course of treatment (weeks 2, 4, and 6), and 6 weeks after the end of treatment. We allocated patients with complete clinical tumour regression, negative tumour site biopsies, and no nodal or distant metastases on CT and MRI 6 weeks after treatment to the observation group (watchful waiting). We referred all other patients to standard surgery. Patients under observation were followed up closely with endoscopies and selected-site biopsies, with surgical resection given for local recurrence. The primary endpoint was local tumour recurrence 1 year after allocation to the observation group. This study is registered with ClinicalTrials.gov, number NCT00952926. Enrolment is closed, but follow-up continues for secondary endpoints. Between Oct 20, 2009, and Dec 23, 2013, we enrolled 55 patients. Patients were recruited from three surgical units throughout Denmark and treated in one tertiary cancer centre (Vejle Hospital, Vejle, Denmark). Of 51 patients who were eligible, 40 had clinical complete response and were allocated to observation. Median follow-up for local recurrence in the observation group was 23·9 months (IQR 15·3-31·0). Local recurrence in the

  8. Sequential memory: Binding dynamics

    Science.gov (United States)

    Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

    2015-10-01

    Temporal order memories are critical for everyday animal and human functioning. Experiments and our own experience show that the binding or association of various features of an event together and the maintaining of multimodality events in sequential order are the key components of any sequential memories—episodic, semantic, working, etc. We study a robustness of binding sequential dynamics based on our previously introduced model in the form of generalized Lotka-Volterra equations. In the phase space of the model, there exists a multi-dimensional binding heteroclinic network consisting of saddle equilibrium points and heteroclinic trajectories joining them. We prove here the robustness of the binding sequential dynamics, i.e., the feasibility phenomenon for coupled heteroclinic networks: for each collection of successive heteroclinic trajectories inside the unified networks, there is an open set of initial points such that the trajectory going through each of them follows the prescribed collection staying in a small neighborhood of it. We show also that the symbolic complexity function of the system restricted to this neighborhood is a polynomial of degree L - 1, where L is the number of modalities.

  9. Sequential Dependencies in Driving

    Science.gov (United States)

    Doshi, Anup; Tran, Cuong; Wilder, Matthew H.; Mozer, Michael C.; Trivedi, Mohan M.

    2012-01-01

    The effect of recent experience on current behavior has been studied extensively in simple laboratory tasks. We explore the nature of sequential effects in the more naturalistic setting of automobile driving. Driving is a safety-critical task in which delayed response times may have severe consequences. Using a realistic driving simulator, we find…

  10. Mining compressing sequential problems

    NARCIS (Netherlands)

    Hoang, T.L.; Mörchen, F.; Fradkin, D.; Calders, T.G.K.

    2012-01-01

    Compression based pattern mining has been successfully applied to many data mining tasks. We propose an approach based on the minimum description length principle to extract sequential patterns that compress a database of sequences well. We show that mining compressing patterns is NP-Hard and

  11. Inverse Planned High-Dose-Rate Brachytherapy for Locoregionally Advanced Cervical Cancer: 4-Year Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Tinkle, Christopher L.; Weinberg, Vivian [Department of Radiation Oncology, University of California, San Francisco, California (United States); Chen, Lee-May [Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, California (United States); Littell, Ramey [Gynecologic Oncology, The Permanente Medical Group, San Francisco, California (United States); Cunha, J. Adam M.; Sethi, Rajni A. [Department of Radiation Oncology, University of California, San Francisco, California (United States); Chan, John K. [Gynecologic Oncology, California Pacific Medical Center, San Francisco, California (United States); Hsu, I-Chow, E-mail: ichow.hsu@ucsf.edu [Department of Radiation Oncology, University of California, San Francisco, California (United States)

    2015-08-01

    Purpose: Evaluate the efficacy and toxicity of image guided brachytherapy using inverse planning simulated annealing (IPSA) high-dose-rate brachytherapy (HDRB) boost for locoregionally advanced cervical cancer. Methods and Materials: From December 2003 through September 2009, 111 patients with primary cervical cancer were treated definitively with IPSA-planned HDRB boost (28 Gy in 4 fractions) after external radiation at our institution. We performed a retrospective review of our experience using image guided brachytherapy. Of the patients, 70% had a tumor size >4 cm, 38% had regional nodal disease, and 15% had clinically evident distant metastasis, including nonregional nodal disease, at the time of diagnosis. Surgical staging involving pelvic lymph node dissection was performed in 15% of patients, and 93% received concurrent cisplatin-based chemotherapy. Toxicities are reported according to the Common Terminology Criteria for Adverse Events version 4.0 guidelines. Results: With a median follow-up time of 42 months (range, 3-84 months), no acute or late toxicities of grade 4 or higher were observed, and grade 3 toxicities (both acute and late) developed in 8 patients (1 constitutional, 1 hematologic, 2 genitourinary, 4 gastrointestinal). The 4-year Kaplan-Meier estimate of late grade 3 toxicity was 8%. Local recurrence developed in 5 patients (4 to 9 months after HDRB), regional recurrence in 3 (6, 16, and 72 months after HDRB), and locoregional recurrence in 1 (4 months after HDR boost). The 4-year estimates of local, locoregional, and distant control of disease were 94.0%, 91.9%, and 69.1%, respectively. The overall and disease-free survival rates at 4 years were 64.3% (95% confidence interval [CI] of 54%-73%) and 61.0% (95% CI, 51%-70%), respectively. Conclusions: Definitive radiation by use of inverse planned HDRB boost for locoregionally advanced cervical cancer is well tolerated and achieves excellent local control of disease. However, overall

  12. The carcinogenic risk of high dose total body irradiation in non-human primates

    International Nuclear Information System (INIS)

    Broerse, J.J.; Bartstra, R.W.; Bekkum, D.W. van; Hage, M.H. van der; Zurcher, C.; Zwieten, M.J. van; Hollander, C.F.

    2000-01-01

    High dose total body irradiation (TBI) in combination with chemotherapy, followed by rescue with bone marrow transplantation (BMT), is increasingly used for the treatment of haematological malignancies. With the increasing success of this treatment and its current introduction for treating refractory autoimmune diseases the risk of radiation carcinogenesis is of growing concern. Studies on turnout induction in non-human primates are of relevance in this context since the response of this species to radiation does not differ much from that in man. Since the early sixties, studies have been performed on acute effects in Rhesus monkeys and the protective action of bone marrow transplantation after irradiation with X-rays (average total body dose 6.8 Gy) and fission neutrons (average dose 3.4 Gy). Of those monkeys, which were irradiated and reconstituted with autologous bone marrow, 20 animals in the X-irradiated group and nine animals in the neutron group survived more than 3 years. A group of 21 non-irradiated Rhesus monkeys of a comparable age distribution served as controls. All animals were regularly screened for the occurrence of neoplasms. Complete necropsies were performed after natural death or euthanasia. At post-irradiation intervals of 4-21 years an appreciable number of tumours was observed. In the neutron irradiated group eight out of nine animals died with one or more malignant tumours. In the X-irradiated group this fraction was 10 out of 20. The tumours in the control group, in seven out of the 21 animals, appeared at much older a-e compared with those in the irradiated cohorts. The histogenesis of the tumours was diverse with a preponderance of renal carcinoma, sarcomas among which osteosarcormas, and malignant glomus tumours in the irradiated groups. When corrected for competing risks, the carcinogenic risk of TBI in the Rhesus monkeys is similar to that derived from the studies of the Japanese atomic bomb survivors. The increase of the risk by a

  13. Fractionated high dose rate intraluminal brachytherapy in palliation of advanced esophageal cancer

    International Nuclear Information System (INIS)

    Sur, Ranjan K.; Donde, Bernard; Levin, Victor C.; Mannell, Aylwyn

    1998-01-01

    Purpose: To optimize the dose of fractionated brachytherapy for palliation of advanced esophageal cancer. Methods and Materials: One hundred and seventy-two patients with advanced esophageal cancer were randomized to receive 12 Gy/2 fractions (group A); 16 Gy/2 fractions (group B), and 18 Gy/3 fractions (group C) by high dose rate intraluminal brachytherapy (HDRILBT). Treatment was given weekly and dose prescribed at 1 cm from the source axis. Patients were followed up monthly and assessed for dysphagia relief and development of complications. Results: Twenty-two patients died before completing treatment due to advanced disease and poor general condition. The overall survival was 19.4% at the end of 12 months for the whole group (A--9.8%, B--22.46%, C--35.32%; p > 0.05). The dysphagia-free survival was 28.9% at 12 months for the whole group (A--10.8%, B--25.43%, C--38.95%; p > 0.05). Forty-three patients developed fibrotic strictures needing dilatation (A--5 of 35, B--15 of 60, C--23 of 55; p = 0.032). Twenty-seven patients had persistent luminal disease (A--11, B--6, C--10), 15 of which progressed to fistulae (A--7, B--2, C--6; p = 0.032). There was no effect of age, sex, race, histology, performance status, previous dilation, presenting dysphagia score, presenting weight, grade, tumor length, and stage on overall survival, dysphagia-free, and complication-free survival (p > 0.05). On a multivariate analysis, brachytherapy dose (p = 0.002) and tumor length (p = 0.0209) were found to have a significant effect on overall survival; brachytherapy dose was the only factor that had an impact on local tumor control (p = 0.0005), while tumor length was the only factor that had an effect on dysphagia-free survival (p = 0.0475). When compared to other forms of palliation currently available (bypass surgery, laser, chemotherapy, intubation, external radiotherapy), fractionated brachytherapy gave the best results with a median survival of 6.2 months. Conclusions: Fractionated

  14. Computed Tomography–Planned High-Dose-Rate Brachytherapy for Treating Uterine Cervical Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zolciak-Siwinska, Agnieszka, E-mail: agnieszka.zolciak@wp.pl [Department of Brachytherapy, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Gruszczynska, Ewelina; Bijok, Michal [Department of Medical Physics, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Jonska-Gmyrek, Joanna [Department of Teleradiotherapy, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Dabkowski, Mateusz [Department of Brachytherapy, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Staniaszek, Jagna [Department of Teleradiotherapy, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Michalski, Wojciech [Department of Clinical Trials and Biostatistics, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Kowalczyk, Adam; Milanowska, Katarzyna [Department of Medical Physics, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland)

    2016-09-01

    Purpose: To evaluate the long-term results of computed tomography (CT)–planned high-dose-rate (HDR) brachytherapy (BT) for treating cervical cancer patients. Methods and Materials: CT-planned HDR BT was performed according to the adapted Group European de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) recommendations in 216 consecutive patients with locally advanced cervical cancer, International Federation of Gynecology and Obstetrics (FIGO) stage IB to IVA, who were treated with conformal external beam radiation therapy and concomitant chemotherapy. We analyzed outcomes and late side effects evaluated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Subjective, Objective, Management, Analysis evaluation scoring system and compared them with the results from a historical group. Results: The median age was 56 years (range, 32-83 years). The median follow-up time for living patients was 52 months (range 37-63 months). The 5-year cumulative incidence function for the local recurrence rate for patients with FIGO II and III was 5.5% and 20%, respectively (P=.001). The 5-year rates of overall survival (OS) and disease-free survival (DFS) were 66.4% and 58.5%, respectively. The relative risk of failure for OS and DFS for FIGO III in relation to FIGO II was 2.24 (P=.003) and 2.6 (P=.000) and for lymph node enlargement was 2.3 (P=.002) and 2 (P=.006), respectively. In 2 patients, rectovaginal fistula occurred, and in 1 patient, vesicovaginal fistula occurred without local progression. Comparison of late adverse effects in patients treated according to the GEC-ESTRO recommendations and in the historical group revealed a reduction in fistula formation of 59% and also a reduction in rectal grade 3 to 4 late toxicity of >59%. Conclusions: This is the largest report with mature data of CT-planned BT HDR for the treatment of cervical cancer with good local control and

  15. External beam radiotherapy boosted with high dose rate brachytherapy in completely resected uterine sarcomas. Is this a treatment option?

    Energy Technology Data Exchange (ETDEWEB)

    Pellizzon, Antonio Cassio Assis; Novaes, Paulo Eduardo Ribeiro dos Santos; Maia, Maria Aparecida Conte; Ferrigno, Robson; Fogarolli, Ricardo; Salvajoli, Joao Vitor [Hospital de Cancer A.C. Camargo, Sao Paulo, SP (Brazil). Dept. de Oncologia de Radiacao]. E-mail: pellizzon@aol.com

    2005-04-15

    Uterine sarcoma (US) is a relative rare tumor, which accounts for only about 3-5% of all uterine cancers. Aggressive cytoreductive surgery at the time of the initial diagnosis with maximum tumor debulking may lead to a prolonged survival or cure. Objective: to identify and review the role of adjuvant external beam radiation therapy (EBRT) associated with high dose rate brachytherapy (HDRB) in the management of patients presenting US with complete resection. Material and methods: this study is a retrospective analysis of 23 patients with US treated from 10/92 to 03/03, with surgery, external beam radiation therapy (EBRT) and high dose rate brachytherapy (HDRB). The inclusion criteria for study participation included: histologically proven and graded US, completely resection of tumor, Karnofsky status 60-100, absence of significant infection, and recovery from recent surgery. Results: The median age of patients was 62 years (range 39-84); ten-year actuarial disease-free and overall survivals were 42.2% and 63.4%, respectively. On univariate analysis, predictive factors for disease-free survival (DFS) were age at initial presentation (p=0.0268), parity (p=0.0441), tumor grade (p= 0.0095), cervical or vaginal invasion (p=0.0014) and node dissection at time of surgery (p= 0.0471). On multivariate analysis, the only predictive factor was cervical or vaginal invasion (p= 0.048), hazard ratio of 4.7. Conclusion: it is quite likely that neither radiotherapy nor chemotherapy alone will appreciably improve survival in US. If radiation therapy provides better locoregional tumor control, hematogenous metastases will assume an even greater proportion of treatment failures. Unfortunately, our small and heterogeneous group analyzed precludes any definitive conclusions about the impact of HDRB associated to EBRT radiation therapy on recurrence or survival. (author)

  16. External beam radiotherapy boosted with high dose rate brachytherapy in completely resected uterine sarcomas. Is this a treatment option?

    International Nuclear Information System (INIS)

    Pellizzon, Antonio Cassio Assis; Novaes, Paulo Eduardo Ribeiro dos Santos; Maia, Maria Aparecida Conte; Ferrigno, Robson; Fogarolli, Ricardo; Salvajoli, Joao Vitor

    2005-01-01

    Uterine sarcoma (US) is a relative rare tumor, which accounts for only about 3-5% of all uterine cancers. Aggressive cytoreductive surgery at the time of the initial diagnosis with maximum tumor debulking may lead to a prolonged survival or cure. Objective: to identify and review the role of adjuvant external beam radiation therapy (EBRT) associated with high dose rate brachytherapy (HDRB) in the management of patients presenting US with complete resection. Material and methods: this study is a retrospective analysis of 23 patients with US treated from 10/92 to 03/03, with surgery, external beam radiation therapy (EBRT) and high dose rate brachytherapy (HDRB). The inclusion criteria for study participation included: histologically proven and graded US, completely resection of tumor, Karnofsky status 60-100, absence of significant infection, and recovery from recent surgery. Results: The median age of patients was 62 years (range 39-84); ten-year actuarial disease-free and overall survivals were 42.2% and 63.4%, respectively. On univariate analysis, predictive factors for disease-free survival (DFS) were age at initial presentation (p=0.0268), parity (p=0.0441), tumor grade (p= 0.0095), cervical or vaginal invasion (p=0.0014) and node dissection at time of surgery (p= 0.0471). On multivariate analysis, the only predictive factor was cervical or vaginal invasion (p= 0.048), hazard ratio of 4.7. Conclusion: it is quite likely that neither radiotherapy nor chemotherapy alone will appreciably improve survival in US. If radiation therapy provides better locoregional tumor control, hematogenous metastases will assume an even greater proportion of treatment failures. Unfortunately, our small and heterogeneous group analyzed precludes any definitive conclusions about the impact of HDRB associated to EBRT radiation therapy on recurrence or survival. (author)

  17. The prediction of late rectal complications in patients treated with high dose-rate brachytherapy for carcinoma of the cervix

    International Nuclear Information System (INIS)

    Clark, Brenda G.; Souhami, Luis; Roman, Ted N.; Chappell, Rick; Evans, Michael D.C.; Fowler, Jack F.

    1997-01-01

    Purpose: The aim of this work is to investigate an unusually high rate of late rectal complications in a group of 43 patients treated with concomitant irradiation and chemotherapy for carcinoma of the cervix between December 1988 and April 1991, with a view to identifying predictive factors. Methods and Materials: The biologically effective dose received by each patient to the rectal reference point defined by the International Commission of Radiation Units and Measurements, Report 38, were calculated. Radiotherapy consisted of 46 Gy external beam irradiation plus three high dose-rate intracavitary treatments of 10 Gy each prescribed to point A. Cisplatin 30 mg/m 2 was given weekly throughout the duration of the irradiation. The results have been compared to data from 119 patients treated with irradiation alone to assess the confounding effect of the cisplatin. Results: The relationship between the biologically effective dose delivered to the rectal reference point and the development of late complications shows a strong dose-response with a threshold for complications occurring at approximately 125 Gy 3 corresponding to a brachytherapy dose of approximately 8 Gy per fraction. This value is approximately the same biologically effective dose threshold as that found for external beam irradiation in the head and neck region. The data from the group of patients treated without cisplatin is comparable to the data from the first group of patients in the lower dose ranges; the higher doses were not used and thus are not available for comparison. Conclusion: Using the linear quadratic model applied to our clinical results, we have established a threshold for late rectal complications for patients treated with external beam irradiation and high dose-rate brachytherapy for carcinoma of the cervix. This threshold is consistent with similar data for external beam irradiation in the head and neck region

  18. Results of a Prospective Study of High-Dose or Conventional Anthracycline-Cyclophosphamide Regimen Plus Radiotherapy for Localized Adult Non-Hodgkin’s Primary Bone Lymphoma

    Directory of Open Access Journals (Sweden)

    A. Schmidt-Tanguy

    2014-01-01

    Full Text Available Background. Primary bone lymphoma (PBL is a rare entity that has only been reviewed in one prospective and small retrospective studies, from which it is difficult to establish treatment guidelines. We prospectively evaluated high-dose or conventional anthracycline-cyclophosphamide dose and radiotherapy for PBL. Patients and Methods. The GOELAMS prospective multicenter study (1986–1998 enrolled adults with localized high-grade PBL according to age and performance status (PS. Patients <60 years received a high-dose CHOP regimen (VCAP and those ≥60 years a conventional anthracycline-cyclophosphamide regimen (VCEP-bleomycin; all received intrathecal chemotherapy and local radiotherapy. Results. Among the 26 patients included (VCAP: 19; VCEP-bleomycin: 7, 39% had poor PS ≥2. With a median follow-up of 8 years, overall survival, event-free survival, and relapse-free survival were 64%, 62%, and 65%, respectively, with no significant difference between treatment groups. Poor PS was significantly associated with shorter OS and EFS. Conclusions. Our results confirm the efficacy of our age-based therapeutic strategy. High-doses anthracycline-cyclophosphamide did not improve the outcome. VCEP-bleomycin is effective and well tolerated for old patients. The intensification must be considered for patients with PS ≥2, a poor prognostic factor.

  19. Curative high dose rate vaginal apex brachytherapy in stage I papillary serous carcinoma of the endometrium

    International Nuclear Information System (INIS)

    Turner, B.C.; Kacinski, B.M.; Gumbs, A.; Peschel, R.E.; Haffty, B.G.; Wilson, L.D.

    1996-01-01

    Introduction: Uterine papillary serous carcinoma (UPSC) is a morphologically distinct variant of endometrial carcinoma that is associated with a poor prognosis, high recurrence rate, clinical understaging, and poor response to salvage treatment. We describe the presentation, local and distant control, survival, salvage rate, and complications for patients undergoing whole abdominal radiation therapy (WART), low dose rate (LDR) intracavitary brachytherapy, or high dose rate (HDR) vaginal brachytherapy in patients with stage I UPSC. Methods: Between 1976 and 1994 more than 1700 patients with endometrial carcinoma were treated with radiation therapy, 30 patients with stage I UPSC (1.8%) were treated with radiation before or following TAH/BSO. All patients underwent either preoperative Simon's packing or tandem and plaque which delivered 30-40 Gy to the serosa, WART, or HDR Ir-192 vaginal apex brachytherapy to a total dose of 21 Gy in 3 fractions at 0.5 cm from the vaginal mucosa. A total of 14 patients received HDR vaginal brachytherapy and (5(14)) patients received systemic chemotherapy. All patients presented with vaginal bleeding at a median age of 67 years (range 34-88). The group of 30 patients underwent TAH/BSO, 17 patients were completely staged pathologically (pelvic and para-aortic lymph nodes, omentectomy, and pelvic washings), and 2 patients underwent omental biopsy and pelvic washings only. All specimens revealed UPSC, nuclear grade 3, and lymphovascular invasion (23%). The pathologic stage was IA: 23% (7), IB: 67% (20), and IC: 10% (3). The median follow-up for all patients was 49 months (range 13-187 months). For the patients receiving postoperative HDR vaginal brachytherapy the median time from surgery to radiation was 42 days (range 29-91). Results: The 5-year actuarial disease free survival for Figo stage I UPSC patients treated with postoperative HDR vaginal brachytherapy and systemic chemotherapy was 100% compared to 74% for stage I UPSC patient

  20. Radioablation of liver malignancies with interstitial high-dose-rate brachytherapy. Complications and risk factors

    Energy Technology Data Exchange (ETDEWEB)

    Mohnike, Konrad; Wolf, Steffen; Damm, Robert; Seidensticker, Max; Seidensticker, Ricarda; Fischbach, Frank; Pech, Maciej; Ricke, Jens [Otto-von-Guericke-Universitaet, Klinik fuer Radiologie und Nuklearmedizin, Universitaetsklinikum Magdeburg A.oe.R., Magdeburg (Germany); Peters, Nils; Hass, Peter; Gademann, Guenther [Otto-von-Guericke-Universitaet, Klinik fuer Strahlentherapie, Universitaetsklinikum Magdeburg A.oe.R., Magdeburg (Germany)

    2016-05-15

    To evaluate complications and identify risk factors for adverse events in patients undergoing high-dose-rate interstitial brachytherapy (iBT). Data from 192 patients treated in 343 CT- or MRI-guided interventions from 2006-2009 at our institution were analyzed. In 41 %, the largest tumor treated was ≥ 5 cm, 6 % of the patients had tumors ≥ 10 cm. Prior to iBT, 60 % of the patients had chemotherapy, 22 % liver resection, 19 % thermoablation or transarterial chemoembolization (TACE). Safety was the primary endpoint; survival data were obtained as the secondary endpoints. During follow-up, MRI or CT imaging was performed and clinical and laboratory parameters were obtained. The rate of major complications was below 5 %. Five major bleedings (1.5 %) occurred. The frequency of severe bleeding was significantly higher in patients with advanced liver cirrhosis. One patient developed signs of a nonclassic radiation-induced liver disease. In 3 patients, symptomatic gastrointestinal (GI) ulcers were detected. A dose exposure to the GI wall above 14 Gy/ml was a reliable threshold to predict ulcer formation. A combination of C-reactive protein ≥ 165 mg/l and/or leukocyte count ≥ 12.7 Gpt/l on the second day after the intervention predicted infection (sensitivity 90.0 %; specificity 92.8 %.) Two patients (0.6 %) died within 30 days. Median overall survival after the first liver treatment was 20.1 months for all patients and the local recurrence-free surviving proportion was 89 % after 12 months. Image-guided iBT yields a low rate of major complications and is effective. (orig.) [German] Evaluierung der Komplikationsrate und Identifizierung von Risikofaktoren fuer Komplikationen und Nebenwirkungen bei Patienten mit Lebermalignomen, die mit der hochdosierten interstitiellen Brachytherapie (iBT) behandelt wurden. Von 2006 bis 2009 wurden 192 Patienten in 343 CT- oder MRT-gefuehrten Interventionen behandelt und deren Daten ausgewertet. Der groesste behandelte Tumor war in

  1. Adjuvant high-dose-rate brachytherapy after external beam radiotherapy in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Oezyar, Enis; Yildz, Ferah; Akyol, Fadil H.; Atahan, I. Lale

    2002-01-01

    Purpose: To compare the local control and survival rates obtained with either external beam radiation therapy (ERT) and adjuvant high-dose-rate (HDR) brachytherapy (BRT) or ERT alone in patients with nasopharyngeal cancer. Methods and Materials: Between December 1993 and December 1999, 144 patients (106 male, 38 female) with the diagnosis of nasopharyngeal cancer were treated with either ERT and adjuvant HDR BRT (Group A) or ERT alone (Group B) at our department. BRT was not applied in 38 patients for the following reasons: (1) Unit was unavailable (n=13), (2) Patient was younger than 18 years (n=17), (3) Patient received accelerated hyperfractionated ERT (n=6), and (4) Patient refused BRT (n=2). The median age for whole group was 43 (range: 9-82 years). According to the AJCC-1997 staging system, there were 11 (7.6%), 35 (24.3%), 38 (26.4%), and 60 (41.7%) patients in Stage I, II, III, and IV, respectively. There were 57 (39.6%) patients with T1, 41 (28.5%) with T2, 20 (13.9%) with T3, and 26 (18.1%) with T4 tumors. Histopathologic diagnosis was WHO 2-3 in 137 (95.2%) patients. ERT doses ranged between 58.8 and 74 Gy (median: 66 Gy). There were significantly more patients with young age, N2 status, and Stage III disease in Group B and with Stage II disease in Group A. Significantly more patients received chemotherapy in Group B. BRT with an HDR 192 Ir microSelectron afterloading unit was delivered in 106 patients at the conclusion of ERT using a single-channel nasal applicator. Dose was prescribed at 1 cm from the source, and total dose of 12 Gy in 3 fractions on 3 consecutive days was given immediately after ERT. Besides radiotherapy, 82 (56.9%) patients received cisplatin-based chemotherapy, as well. Follow-up time ranged between 12 and 80 months (median: 32 months). Results: The two groups were comparable in terms of local recurrence, locoregional failure, regional failure, and rate of distant metastasis. Local failure was observed in 11 (10.3%) out of 106

  2. Efficacy and tolerability of high-dose phenobarbital in children with focal seizures.

    Science.gov (United States)

    Okumura, Akihisa; Nakahara, Eri; Ikeno, Mitsuru; Abe, Shinpei; Igarashi, Ayuko; Nakazawa, Mika; Takasu, Michihiko; Shimizu, Toshiaki

    2016-04-01

    We retrospectively reviewed the outcomes of children with focal epilepsy treated with oral high-dose phenobarbital. We reviewed data on children (agedphenobarbital (>5 mg/kg/day to maintain a target serum level >40 μg/mL) for at least 6 months. Seizure frequency was evaluated after phenobarbital titration, and 1 and 2 years after high-dose phenobarbital treatment commenced. Treatment was judged effective when seizure frequencies fell by ⩾75%. Seven boys and eight girls were treated. The median age at commencement of high-dose phenobarbital therapy was 30 months. The maximal serum phenobarbital level ranged from 36.5 to 62.9 μg/mL. High-dose PB was effective in seven. In two patients, treatment was transiently effective, but seizure frequency later returned to the baseline. High-dose PB was ineffective in six. No significant association between effectiveness and any clinical variable was evident. Drowsiness was recorded in nine patients, but no patient developed a behavioral problem or hypersensitivity. Oral high-dose phenobarbital was effective in 7 of 15 patients with focal epilepsy and well tolerated. High-dose PB may be useful when surgical treatment is difficult. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  3. Vorinostat Combined with High-Dose Gemcitabine, Busulfan, and Melphalan with Autologous Stem Cell Transplantation in Patients with Refractory Lymphomas.

    Science.gov (United States)

    Nieto, Yago; Valdez, Benigno C; Thall, Peter F; Ahmed, Sairah; Jones, Roy B; Hosing, Chitra; Popat, Uday; Shpall, Elizabeth J; Qazilbash, Muzaffar; Gulbis, Alison; Anderlini, Paolo; Alousi, Amin; Shah, Nina; Bashir, Qaiser; Liu, Yan; Oki, Yasuhiro; Hagemeister, Frederick; Fanale, Michelle; Dabaja, Bouthaina; Pinnix, Chelsea; Champlin, Richard; Andersson, Borje S

    2015-11-01

    More active high-dose regimens are needed for refractory/poor-risk relapsed lymphomas. We previously developed a regimen of infusional gemcitabine/busulfan/melphalan, exploiting the synergistic interaction. Its encouraging activity in refractory lymphomas led us to further enhance its use as a platform for epigenetic modulation. We previously observed increased cytotoxicity in refractory lymphoma cell lines when the histone deacetylase inhibitor vorinostat was added to gemcitabine/busulfan/melphalan, which prompted us to clinically study this four-drug combination. Patients ages 12 to 65 with refractory diffuse large B cell lymphoma (DLCL), Hodgkin (HL), or T lymphoma were eligible. Vorinostat was given at 200 mg/day to 1000 mg/day (days -8 to -3). Gemcitabine was infused continuously at 10 mg/m(2)/minute over 4.5 hours (days -8 and -3). Busulfan dosing targeted 4000 μM-minute/day (days -8 to -5). Melphalan was infused at 60 mg/m(2)/day (days -3 and -2). Patients with CD20(+) tumors received rituximab (375 mg/m(2), days +1 and +8). We enrolled 78 patients: 52 DLCL, 20 HL, and 6 T lymphoma; median age 44 years (range, 15 to 65); median 3 prior chemotherapy lines (range, 2 to 7); and 48% of patients had positron emission tomography-positive tumors at high-dose chemotherapy (29% unresponsive). The vorinostat dose was safely escalated up to 1000 mg/day, with no treatment-related deaths. Toxicities included mucositis and dermatitis. Neutrophils and platelets engrafted promptly. At median follow-up of 25 (range, 16 to 41) months, event-free and overall survival were 61.5% and 73%, respectively (DLCL) and 45% and 80%, respectively (HL). In conclusion, vorinostat/gemcitabine/busulfan/melphalan is safe and highly active in refractory/poor-risk relapsed lymphomas, warranting further evaluation. This trial was registered at ClinicalTrials.gov (NCI-2011-02891). Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights

  4. A Phase I Trial of High-Dose Lenalidomide and Melphalan as Conditioning for Autologous Stem Cell Transplantation in Relapsed or Refractory Multiple Myeloma.

    Science.gov (United States)

    Mark, Tomer M; Guarneri, Danielle; Forsberg, Peter; Rossi, Adriana; Pearse, Roger; Perry, Arthur; Pekle, Karen; Tegnestam, Linda; Greenberg, June; Shore, Tsiporah; Gergis, Usama; Mayer, Sebastian; Van Besien, Koen; Ely, Scott; Jayabalan, David; Sherbenou, Daniel; Coleman, Morton; Niesvizky, Ruben

    2017-06-01

    Autologous stem cell transplantation (ASCT) conditioned with high-dose chemotherapy has long been established as the standard of care for eligible patients with newly diagnosed multiple myeloma. Despite recent therapeutic advances, high-dose melphalan (HDM) remains the chemotherapy regimen of choice in this setting. Lenalidomide (LEN) in combination with low-dose dexamethasone is recognized as a standard of care for patients with relapsed or refractory multiple myeloma (RRMM), and there is growing support for the administration of LEN as maintenance therapy post-ASCT. In view of the above, the present phase I clinical trial was designed to evaluate the safety and tolerability of high-dose LEN (HDLEN) in patients with RRMM, and to determine the maximum tolerated dose of HDLEN when added to HDM before ASCT. Despite administering HDLEN at doses of up to 350 mg/day, the maximum tolerated dose could not be determined, owing to an insufficient number of dose-limiting toxicities in the 21 patients enrolled in the trial. Conditioning with HDLEN plus HDM was associated with a favorable tolerability profile. Adverse events following ASCT were as expected with HDM. Median progression-free and overall survival were 10 months and 22 months, respectively, in this population of heavily pretreated patients. Our findings suggest that HDLEN in combination with HDM may offer significant potential as a conditioning regimen before ASCT in patients with RRMM. These preliminary findings are now being evaluated further in an ongoing phase II clinical trial. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  5. Erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA

    International Nuclear Information System (INIS)

    Speight, E.L.; Farr, P.M.

    1994-01-01

    In PUVA treatment of psoriasis, clinical observation suggests that uninvolved skin is more susceptible to PUVA erythema than lesions of psoriasis. If this is the case, then the efficacy of PUVA treatment might be increased by using localized high-dose UVA restricted to lesional skin. We have therefore studied the erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA and, for comparison, the erythemal response to UVB. This study demonstrates that psoriasis may clear rapidly, without burning, using high-dose UVA. Availability of a suitable irradiation apparatus would allow rapid and effective PUVA treatment to be used for localized, resistant disease. (author)

  6. Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline

    DEFF Research Database (Denmark)

    Kaae, Rikke; Agertoft, Lone; Pedersen, Sören

    2004-01-01

    OBJECTIVES: To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. METHODS: Twenty boys and girls (6-11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxi...

  7. High-dose therapy and autologous transplantation for lymphoma: the Peter MacCallum Cancer institute experience

    International Nuclear Information System (INIS)

    Dowling, A.J.; Prince, H.M.; Wolf, M.; Januszewicz, H.; Seymour, J.F.; Gates, P.; Wirth, A.; Juneja, S.; Smith, J.G.

    2001-01-01

    High-dose therapy (HDT) with autologous bone marrow or blood cell transplantation for the treatment of lymphoma commenced at Peter MacCallum Cancer Institute in 1986. To examine the patient characteristics and outcomes of patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) treated with HDT and autologous transplantation at our Institute in the first 10 years of the service (1986-95). A retrospective analysis was performed examining patient characteristics, prior chemotherapy regimens, pretransplant disease status, HDT regimen, source of stem cells, time for haematopoietic recovery, complications of transplantation, response rates, overall survival (OS) and progression-free survival (PFS). Sixty-seven patients with NHL were treated with an estimated 5-year OS rate of 44% (95% confidence interval (CI) 32-56%) and PFS rate of 34% (95% CI 21-44%). Factors independently predictive of an unfavourable PFS on multivariate analyses were presence of constitutional symptoms at transplant (P < 0.002) and chemotherapy-resistant disease at transplant (P= 0.02). Twenty-three patients with HD were treated with a 5-year predicted OS rate of 74% (95% CI 56-92%) and PFS rate of 57% (95% CI 36-77%).There was no difference in PFS for HD patients who relapsed either within 12 months of completion of front-line therapy or after this time (P =0.5). The transplant-related mortality for the entire cohort was 17%, with a progressive decrease over time. HDT with autologous transplantation achieves durable PFS and OS in patients with lymphoma. Improved patient selection, therapy modifications according to prognostic factors and ongoing improvements in supportive care should improve outcomes further

  8. Forced Sequence Sequential Decoding

    DEFF Research Database (Denmark)

    Jensen, Ole Riis

    In this thesis we describe a new concatenated decoding scheme based on iterations between an inner sequentially decoded convolutional code of rate R=1/4 and memory M=23, and block interleaved outer Reed-Solomon codes with non-uniform profile. With this scheme decoding with good performance...... is possible as low as Eb/No=0.6 dB, which is about 1.7 dB below the signal-to-noise ratio that marks the cut-off rate for the convolutional code. This is possible since the iteration process provides the sequential decoders with side information that allows a smaller average load and minimizes the probability...... of computational overflow. Analytical results for the probability that the first Reed-Solomon word is decoded after C computations are presented. This is supported by simulation results that are also extended to other parameters....

  9. Sequential Power-Dependence Theory

    NARCIS (Netherlands)

    Buskens, Vincent; Rijt, Arnout van de

    2008-01-01

    Existing methods for predicting resource divisions in laboratory exchange networks do not take into account the sequential nature of the experimental setting. We extend network exchange theory by considering sequential exchange. We prove that Sequential Power-Dependence Theory—unlike

  10. Modelling sequentially scored item responses

    NARCIS (Netherlands)

    Akkermans, W.

    2000-01-01

    The sequential model can be used to describe the variable resulting from a sequential scoring process. In this paper two more item response models are investigated with respect to their suitability for sequential scoring: the partial credit model and the graded response model. The investigation is

  11. Intravenous administration of high-dose Paclitaxel reduces gut-associated lymphoid tissue cell number and respiratory immunoglobulin A concentrations in mice.

    Science.gov (United States)

    Moriya, Tomoyuki; Fukatsu, Kazuhiko; Noguchi, Midori; Okamoto, Koichi; Murakoshi, Satoshi; Saitoh, Daizoh; Miyazaki, Masaru; Hase, Kazuo; Yamamoto, Junji

    2014-02-01

    Chemotherapy remains a mainstay of treatment for cancer patients. However, anti-cancer drugs frequently cause a wide range of side effects, including leukopenia and gastrointestinal toxicity. These adverse effects can lead to treatment delays or necessitate temporary dose reductions. Although chemotherapy-related changes in gut morphology have been demonstrated, the influences of chemotherapeutic regimens on gut immunity are understood poorly. This study aimed to examine whether the anti-cancer drug paclitaxel (PTX) impairs gut immunity in mice. Male ICR mice were randomized into three groups: Control, low-dose PTX (low PTX; 2 mg/kg), or high-dose PTX (high PTX; 4 mg/kg). A single intravenous dose was given. On day seven after the injection, lymphocytes from Peyer patches (PP), intraepithelial (IE) spaces, and the lamina propria (LP) were counted and analyzed by flow cytometry (CD4(+), CD8(+), αβTCR(+), γδTCR(+), B220(+)). Immunoglobulin A (IgA) concentrations were measured in small intestinal and respiratory tract washings. Total, CD4(+) and γδTCR(+) lymphocyte numbers in PPs were significantly lower in the high PTX than in the control group. The CD4(+) lymphocyte numbers in the IE spaces were significantly lower in both PTX groups than in the control group. Respiratory tract IgA concentrations were lower in the high PTX than in the control group. The present data suggest high-dose PTX impairs mucosal immunity, possibly rendering patients more vulnerable to infection. Careful dose selection and new therapies may be important for maintaining mucosal immunity during PTX chemotherapy.

  12. High-dose zolpidem dependence - Psychostimulant effects? A case report and literature review

    Directory of Open Access Journals (Sweden)

    Abhijna Chandan Chattopadhyay

    2016-01-01

    Full Text Available Zolpidem, an imidazoline nonbenzodiazepine sedative drug, is used widely. Initial reports showed minimal abuse potential. However, multiple reports have appeared of dose escalation and abuse. Subjective effects of high-dose zolpidem are not known. In light of accumulating evidence of abuse potential, we hereby report a case of high-dose dependence and a review of relevant literature. A 33-year-old male presented with 5 years of daily use of 600–1700 mg of zolpidem tartrate. He reported subjective effects of euphoria, intense craving, and inability to stop use. Loss of receptor specificity, pharmacokinetic factors, and different receptor distributions can explain paradoxical stimulatory effects of high-dose zolpidem. Further studies are required to characterize subjective effects of high-dose zolpidem.

  13. Acute effects of high-dose furosemide on residual renal function in CAPD patients

    NARCIS (Netherlands)

    van Olden, Rudolf W.; Guchelaar, Henk-Jan; Struijk, Dirk G.; Krediet, Raymond T.; Arisz, Lambertus

    2003-01-01

    BACKGROUND: High doses of furosemide can increase urine volume in chronic peritoneal dialysis (CAPD) patients. However, no information is available about effects on urinary solute excretion in relation to residual glomerular filtration rate (GFR), urinary furosemide excretion, and peritoneal solute

  14. Forced Sequence Sequential Decoding

    DEFF Research Database (Denmark)

    Jensen, Ole Riis; Paaske, Erik

    1998-01-01

    We describe a new concatenated decoding scheme based on iterations between an inner sequentially decoded convolutional code of rate R=1/4 and memory M=23, and block interleaved outer Reed-Solomon (RS) codes with nonuniform profile. With this scheme decoding with good performance is possible as low...... as Eb/N0=0.6 dB, which is about 1.25 dB below the signal-to-noise ratio (SNR) that marks the cutoff rate for the full system. Accounting for about 0.45 dB due to the outer codes, sequential decoding takes place at about 1.7 dB below the SNR cutoff rate for the convolutional code. This is possible since...... the iteration process provides the sequential decoders with side information that allows a smaller average load and minimizes the probability of computational overflow. Analytical results for the probability that the first RS word is decoded after C computations are presented. These results are supported...

  15. A Phase I Study of CPI-613 in Combination with High-Dose Cytarabine and Mitoxantrone for Relapsed or Refractory Acute Myeloid Leukemia.

    Science.gov (United States)

    Pardee, Timothy S; Anderson, Rebecca G; Pladna, Kristin M; Isom, Scott; Ghiraldeli, Lais P; Miller, Lance D; Chou, Jeff W; Jin, Guangxu; Zhang, Wei; Ellis, Leslie R; Berenzon, Dmitriy; Howard, Dianna S; Hurd, David D; Manuel, Megan; Dralle, Sarah; Lyerly, Susan; Powell, Bayard L

    2018-05-01

    Purpose: CPI-613, a lipoate analogue that inhibits pyruvate dehydrogenase (PDH) and α-ketogluterate dehydrogenase (KGDH), has activity in patients with myeloid malignancies. This study explored the role of mitochondrial metabolism in chemotherapy response and determined the MTD, efficacy, and safety of CPI-613 combined with high-dose cytarabine and mitoxantrone in patients with relapsed or refractory acute myeloid leukemia. Experimental Design: The role of mitochondrial response to chemotherapy was assessed in cell lines and animal models. A phase I study of CPI-613 plus cytarabine and mitoxantrone was conducted in patients with relapsed or refractory AML. Results: Exposure to chemotherapy induced mitochondrial oxygen consumption that depended on PDH. CPI-613 sensitized AML cells to chemotherapy indicating that mitochondrial metabolism is a source of resistance. Loss of p53 did not alter response to CPI-613. The phase I study enrolled 67 patients and 62 were evaluable for response. The overall response rate was 50% (26CR+5CRi/62). Median survival was 6.7 months. In patients over 60 years old, the CR/CRi rate was 47% (15/32) with a median survival of 6.9 months. The response rate for patients with poor-risk cytogenetics also was encouraging with 46% (11/24 patients) achieving a CR or CRi. RNA sequencing analysis of a subset of baseline bone marrow samples revealed a gene expression signature consistent with the presence of B cells in the pretreatment marrow of responders. Conclusions: The addition of CPI-613 to chemotherapy is a promising approach in older patients and those with poor-risk cytogenetics. Clin Cancer Res; 24(9); 2060-73. ©2018 AACR . ©2018 American Association for Cancer Research.

  16. Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration

    OpenAIRE

    McFadden, Lisa M; Hoonakker, Amanda J; Vieira-Brock, Paula L; Stout, Kristen A; Sawada, Nicole M; Ellis, Jonathan D; Allen, Scott C; Walters, Elliot T; Nielsen, Shannon M; Gibb, James W; Alburges, Mario E; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2011-01-01

    Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent (i.e., postnatal day (PND) 40) rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a “challenge” high-dose METH regimen when administered ...

  17. Safety aspects of preoperative high-dose glucocorticoid in primary total knee replacement

    DEFF Research Database (Denmark)

    Jørgensen, C C; Pitter, F T; Kehlet, H

    2017-01-01

    Background: Preoperative single high-dose glucocorticoid may have early outcome benefits in total hip arthroplasty (THA) and knee arthroplasty (TKA), but long-term safety aspects have not been evaluated. Methods: From October 2013, the departments reporting to the prospective Lundbeck Foundation....... Conclusions: In this detailed prospective cohort study, preoperative high-dose glucocorticoid administration was not associated with LOS >4 days, readmissions or infectious complications in TKA patients without contraindications....

  18. Evaluation of functioning of high dose rate brachytherapy at the Instituto Nacional do Cancer

    International Nuclear Information System (INIS)

    Guedes, Laura M.A.; Barreto, Rodrigo V.; Silva, Penha M.; Macedo, Afranio A.; Borges, Solange C.; Martinez, Valeria P.O.

    2001-01-01

    Quality control tests are very useful tools to assure the quality of patient's treatment. A daily control of the high dose rate micro selectron was performed based on the security parameters of the equipment and on the quickness of performance. The purpose of this report is to evaluate and to discuss the errors found during the first three years with the high dose rate brachytherapy, at the Instituto Nacional de Cancer. (author)

  19. High-dose Sulbactam Treatment for Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant

    Directory of Open Access Journals (Sweden)

    In Beom Jeong

    2016-11-01

    Full Text Available Background Several antibiotics can be used to treat ventilator-associated pneumonia caused by carbapenem-resistant A. baumannii (CRAB-VAP including high-dose sulbactam. However, the effectiveness of high-dose sulbactam therapy is not well known. We report our experience with high-dose sulbactam for treatment of CRAB-VAP. Methods Medical records of patients with CRAB-VAP who were given high-dose sulbactam between May 2013 and June 2015 were reviewed. Results Fifty-eight patients with CRAB-VAP were treated with high-dose sulbactam. The mean age was 72.0 ± 15.2 years, and the acute physiology and chronic health evaluation II (APACHE II score was 15.1 ± 5.10 at the time of CRAB-VAP diagnosis. Early clinical improvement was observed in 65.5% of patients, and 30-day mortality was 29.3%. Early clinical failure (odds ratio [OR]: 8.720, confidence interval [CI]: 1.346-56.484; p = 0.023 and APACHE II score ≥ 14 at CRAB-VAP diagnosis (OR: 10.934, CI: 1.047-114.148; p = 0.046 were associated with 30-day mortality. Conclusions High-dose sulbactam therapy may be effective for the treatment of CRAB-VAP. However, early clinical failure was observed in 35% of patients and was associated with poor outcome.

  20. Transperineal high-dose-rate interstitial radiation therapy in the management of gynecologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Itami, Jun; Hara, Ryuseke; Kozuka, Takuyou; Yamashita, Hideomi; Nakajima, Kaori; Shibata, Kouji; Abe, Yoshihisa; Fuse, Masashi; Ito, Masashi [International Medical Center of Japan, Tokyo (Japan). Dept. of Radiation Therapy and Oncology

    2003-11-01

    Background: High-dose-rate interstitial radiation therapy is a newly introduced modality, and its role in the management of gynecologic malignancies remains to be studied. Clinical experience in high-dose-rate interstitial radiation therapy was retrospectively investigated. Patients and Methods: Eight patients with primary and nine with recurrent gynecologic malignancies underwent high-dose-rate interstitial radiation therapy with/without external-beam irradiation. Fractional dose of the high-dose-rate interstitial radiation therapy ranged between 4 and 6 Gy with total doses of 15-54 Gy. Interstitial irradiation was performed twice daily with an interval of > 6 h. Results: 2-year local control rate was 75% for primary treatment and 47% for treatment of recurrence (p = 0.46). Maximum tumor size had a statistically significant impact on local control (p < 0.002). Grade 2 and 4 late complications were seen in five patients, and the incidence was significantly higher in patients with a larger volume enclosed by the prescribed fractional dose of high-dose-rate interstitial radiation therapy. The incidence of grade 2 and 4 complications at 18 months was 78% and 0% with a volume > 100 cm{sup 3} and {<=} 100 cm{sup 3}, respectively (p < 0.04). Conclusion: Although high-dose-rate interstitial radiation therapy is a promising modality, it must be applied cautiously to patients with bulky tumors because of the high incidence of serious complications. (orig.)

  1. Administration of Concurrent Vaginal Brachytherapy During Chemotherapy for Treatment of Endometrial Cancer

    International Nuclear Information System (INIS)

    Nagar, Himanshu; Boothe, Dustin; Parikh, Amar; Yondorf, Menachem; Parashar, Bhupesh; Gupta, Divya; Holcomb, Kevin; Caputo, Thomas; Chao, K. S. Clifford; Nori, Dattatreyudu; Wernicke, A. Gabriella

    2013-01-01

    Purpose: To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. Methods and Materials: A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB + external beam RT (EBRT) + 6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. Results: Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P .05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. Conclusions: VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen

  2. Chemotherapy disruption of efficient radiotherapy

    International Nuclear Information System (INIS)

    Nervi, C.; Friedman, M.

    1974-01-01

    Studies on the use of chemotherapy in combination with radiotherapy are reviewed. Some topics discussed are: indications for the use of combined chemotherapy and radiotherapy; improvement of the therapeutic ratio following the use of methotrexate; advantages of preirradiation and postirradiation chemotherapy; side effects following simultaneous chemotherapy and radiotherapy; and effects of chemotherapy on cure rate of radiosensitive and radioresistant tumors. (U.S.)

  3. Tolerability in the elderly population of high-dose alpha lipoic acid: a potential antioxidant therapy for the eye

    Directory of Open Access Journals (Sweden)

    Sarezky D

    2016-09-01

    Full Text Available Daniel Sarezky, Aaishah R Raquib, Joshua L Dunaief, Benjamin J Kim Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Purpose: Alpha lipoic acid (ALA is an antioxidant and iron-chelating supplement that has potential benefits for geographic atrophy in dry age-related macular degeneration as well as other eye diseases. The purpose of this study was to determine the tolerability of ALA in the elderly population. Patients and methods: Fifteen subjects, age ≥65 years, took sequential ALA doses of 600, 800, and 1,200 mg. Each dose was taken once daily with a meal for 5 days. After each dose was taken by the subjects for 5 days, the subjects were contacted by phone, a review of systems was performed, and they were asked if they thought they could tolerate taking that dose of ALA for an extended period of time. Results: The 600 mg dose was well tolerated. At the 800 mg dose, one subject had an intolerable flushing sensation. At the 1,200 mg dose, two subjects had intolerable upper gastrointestinal side effects and one subject had an intolerable flushing sensation. Subjects taking gastrointestinal prophylaxis medications had no upper gastrointestinal side effects. Conclusion: High-dose ALA is not completely tolerated by the elderly. These preliminary data suggest that gastrointestinal prophylaxis may improve tolerability. (ClinicalTrials.gov, NCT02613572. Keywords: age-related macular degeneration, geographic atrophy, antioxidant, gastrointestinal, dietary supplements, lipoic acid

  4. Germ cell tumors of testis; an update in chemotherapy treatment

    International Nuclear Information System (INIS)

    Parvez, T.

    2002-01-01

    Prior to the use of cisplatin, durable complete remission of metastatic testicular cancer were rare. In 1977, a chemotherapy treatment program including cisplatin, vinblastine, and bleomycin (PVB) let to high response rates and acceptable toxicity in patients with disseminated testicular cancer. After that, bleomycin, etoposide, and cisplatin (BEP) chemotherapy regimen was established as a standard therapy for good- and poor-risk disease and further, ifosfamide-based regimens or high-dose chemotherapy with stem cell rescue as the salvage therapy. The results of these prospective, randomized clinical trials that have markedly improved the outlook of patients with this type of cancer have been reviewed in this article. While the present state-of-the-art treatment for metastatic testicular cancer is promising approximately one-third of patients with poor risk disease will not achieve a remission. Trials of new agents and approaches are needed to increase the patient survival. (author)

  5. Sequential decay of Reggeons

    International Nuclear Information System (INIS)

    Yoshida, Toshihiro

    1981-01-01

    Probabilities of meson production in the sequential decay of Reggeons, which are formed from the projectile and the target in the hadron-hadron to Reggeon-Reggeon processes, are investigated. It is assumed that pair creation of heavy quarks and simultaneous creation of two antiquark-quark pairs are negligible. The leading-order terms with respect to ratio of creation probabilities of anti s s to anti u u (anti d d) are calculated. The production cross sections in the target fragmentation region are given in terms of probabilities in the initial decay of the Reggeons and an effect of manyparticle production. (author)

  6. Mobilizing peripheral blood stem cells with high-dose G-CSF alone is as effective as with Dexa-BEAM plus G-CSF in lymphoma patients.

    Science.gov (United States)

    Kröger, N; Zeller, W; Fehse, N; Hassan, H T; Krüger, W; Gutensohn, K; Lölliger, C; Zander, A R

    1998-09-01

    We compared retrospectively the efficacy of granulocyte colony stimulating factor (G-CSF) alone with chemotherapy plus G-CSF in mobilizing CD34-positive cells in patients with malignant lymphoma. 35 patients underwent peripheral blood stem cell (PBSC) collection following mobilization either with 24 microg/kg G-CSF for 4 consecutive days (n = 18) or Dexa-BEAM chemotherapy plus 5 microg/kg G-CSF (n = 17). High-dose G-CSF was well tolerated with only slight bone pain and/or myalgia. The Dexa-BEAM therapy required hospitalization with a median duration of 21 d. The median number of apheresis procedures in both groups was two (range two to four), resulting in a median of 5.3 and 5.1 x 10(6) CD34+ cells/kg. No patients in the G-CSF group, but one in the Dexa-BEAM group, failed to reach the target of collecting >2.0 x 10(6) CD34+ cells/kg. The number of CFU-GM (10.4 v 6.0 x 10(5)/kg) and of BFU-E (10.6 v 4.5 x 10(5)/kg; P = 0.04) was higher in the G-CSF group than in the Dexa-BEAM group. A subset analysis of CD34+ cells was performed in 16 patients showing a higher mean of Thy-1 (CD90w) coexpression in the G-CSF than in the Dexa-BEAM group (4.8 v 1.8%, P = 0.12). Additionally the percentage of CD34+/CD38- cells was higher in the G-CSF group (10.66% v 8.8%). However, these differences were not statistically significant. The median time to leucocyte and platelet engraftment after high-dose chemotherapy was slightly shorter in the G-CSF than in the Dexa-BEAM group (9 v 10 and 12 v 13.5 d, respectively). These results demonstrate that high-dose G-CSF is as effective as Dexa-BEAM plus G-CSF in mobilizing peripheral blood stem cells and produces prompt engraftment. The major advantages of G-CSF mobilization were the safe outpatient self-application and the fixed-day apheresis.

  7. High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group.

    Science.gov (United States)

    Pritchard, Jon; Cotterill, Simon J; Germond, Shirley M; Imeson, John; de Kraker, Jan; Jones, David R

    2005-04-01

    High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma. In this study (European Neuroblastoma Study Group, ENSG1), the value of melphalan myeloablative "megatherapy" was evaluated in a randomised, multi-centre trial. Between 1982 and 1985, 167 children with stages IV and III neuroblastoma (123 stage IV > 1 year old at diagnosis and 44 stage III and stage IV from 6 to 12 months old at diagnosis) were treated with oncovin, cisplatin, epipodophyllotoxin, and cyclophosphamide (OPEC) induction chemotherapy every 3 weeks. After surgical excision of primary tumour, the 90 patients (69% of the total) who achieved complete response (CR) or good partial response (GPR) were eligible for randomisation either to high dose melphalan (180 mg per square meter) with autologous bone marrow support or to no further treatment. Sixty-five (72%) of eligible children were actually randomised and 21 of these patients were surviving at time of this analysis, with median follow-up from randomisation of 14.3 years. Five year event-free survival (EFS) was 38% (95% confidence interval (CI) 21-54%) in the melphalan-treated group and 27% (95% CI 12-42%) in the "no-melphalan" group. This difference was not statistically significant (P = 0.08, log rank test) but for the 48 randomised stage IV patients aged >1 year at diagnosis outcome was significantly better in the melphalan-treated group-5 year EFS 33% versus 17% (P = 0.01, log rank test). In this trial, high dose melphalan improved the length of EFS and overall survival of children with stage IV neuroblastoma >1 year of age who achieved CR or GPR after OPEC induction therapy and surgery. Multi-agent myeloablative regimens are now widely used as consolidation therapy for children with stage IV disease and in those with other disease stages when the MYCN gene copy number in tumour cells is amplified

  8. Postoperative Chemotherapy for Medulloblastoma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-03-01

    Full Text Available The survival rate and cognitive function of 43 children, age <3 years, with medulloblastoma treated with intensive postoperative chemotherapy alone, without radiotherapy, were determined at the University of Wurzburg and other centers in Germany Chemotherapy consisted of three two-month cycles of cyclophosphamide, methotrexate, vincristine, carboplatin, and etoposide.

  9. Endobronchial and endoesophageal high dose rate brachytherapy for malignant airway and digestive tract obstructions

    International Nuclear Information System (INIS)

    Mehta, Minesh P.

    1996-01-01

    With an annual incidence of more than 160,000 cases and a local failure rate between 30-50%, endobronchial occlusion seen with lung cancer is a common and potentially life-threatening complication. Several methods of managing this exist and recently endobronchial brachytherapy has been used extensively as a consequence of the development of fiberoptic bronchoscopy and high dose rate remote afterloading technology. Procedurally, one or more afterloading catheters are inserted in the involved portions of the tracheobronchial tree through fiberoptic guidance. Treatment techniques range from 1-4 applications fractionated over several weeks or given over 2 days with a single insertion procedure. Almost all procedures are currently performed in the outpatient setting. The major application of this technology is in the palliation of occlusive symptomatology. Clinical improvement ranges from 50-100%, radiographic reaeration ranges from 46-88% and bronchoscopic responses ranges from 59-100%. Symptomatic relief is usually quite durable with more than 70% of the patients' remaining life-time rendered symptom-free and symptom-improved. Recently, this modality has been explored for its curative potential as a boost following external beam radiotherapy. It is clear from these series, that in selected patients, endobronchial boost produces significant reaeration and sparing of lung volume from subsequent external radiation, and a few cases may even become resectable. Demonstration of the survival advantage will, however, require larger clinical trials with adequate controls. Some reports have suggested an unacceptably high rate of fatal hemoptysis following HDR endobronchial brachytherapy. Review of the world literature suggests that fatal hemoptysis rates range from 0-50% with an average of about 8%, comparable to an average of 5% with low dose rate brachytherapy. Other recognized complications include fistulae and radiation bronchitis. Because the majority of patients with

  10. Synthetic Aperture Sequential Beamforming

    DEFF Research Database (Denmark)

    Kortbek, Jacob; Jensen, Jørgen Arendt; Gammelmark, Kim Løkke

    2008-01-01

    A synthetic aperture focusing (SAF) technique denoted Synthetic Aperture Sequential Beamforming (SASB) suitable for 2D and 3D imaging is presented. The technique differ from prior art of SAF in the sense that SAF is performed on pre-beamformed data contrary to channel data. The objective is to im......A synthetic aperture focusing (SAF) technique denoted Synthetic Aperture Sequential Beamforming (SASB) suitable for 2D and 3D imaging is presented. The technique differ from prior art of SAF in the sense that SAF is performed on pre-beamformed data contrary to channel data. The objective...... is to improve and obtain a more range independent lateral resolution compared to conventional dynamic receive focusing (DRF) without compromising frame rate. SASB is a two-stage procedure using two separate beamformers. First a set of Bmode image lines using a single focal point in both transmit and receive...... is stored. The second stage applies the focused image lines from the first stage as input data. The SASB method has been investigated using simulations in Field II and by off-line processing of data acquired with a commercial scanner. The performance of SASB with a static image object is compared with DRF...

  11. High dose vitamin D may improve lower urinary tract symptoms in postmenopausal women.

    Science.gov (United States)

    Oberg, Johanna; Verelst, Margareta; Jorde, Rolf; Cashman, Kevin; Grimnes, Guri

    2017-10-01

    Lower urinary tract symptoms (LUTS) are common in postmenopausal women, and have been reported inversely associated with vitamin D intake and serum 25-hydroxyvitamin D (25(OH)D) levels. The aim of this study was to investigate if high dose vitamin D supplementation would affect LUTS in comparison to standard dose. In a randomized controlled study including 297 postmenopausal women with low bone mineral density, the participants were allocated to receive capsules of 20 000IU of vitamin D 3 twice a week (high dose group) or similar looking placebo (standard dose group). In addition, all the participants received 1g of calcium and 800IU of vitamin D daily. A validated questionnaire regarding LUTS was filled in at baseline and after 12 months. At baseline, 76 women in the high dose group and 82 in the standard dose group reported any LUTS. Levels of serum 25(OH)D increased significantly more in the high dose group (from 64.7 to 164.1nmol/l compared to from 64.1 to 81.8nmol/l, p<0.01). No differences between the groups were seen regarding change in LUTS except for a statistically significant reduction in the reported severity of urine incontinence in the high dose group as compared to the standard dose group after one year (p<0.05). The results need confirmation in a study specifically designed for this purpose. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. High-dose gadolinium-enhanced MRI for diagnosis of meningeal metastases

    International Nuclear Information System (INIS)

    Kallmes, D.F.; Gray, L.; Glass, J.P.

    1998-01-01

    We compared high-dose (0.3 mmol/kg) and standard-dose (0.1 mmol/kg) gadolinium-enhanced MRI for diagnosis of meningeal metastases in 12 patients with suspected meningeal metastases. They were imaged with both standard-dose and high-dose gadolinium. All patients with abnormal meningeal enhancement underwent at least one lumbar puncture for cerebrospinal fluid (CSF) cytology, while patients with normal meningeal enhancement were followed clinically. All patients with negative CSF cytology also were followed clinically. A single observer reviewed all the images, with specific attention to the enhancement pattern of the meninges. Abnormal leptomeningeal enhancement was present in three cases, and abnormal pachymeningeal enhancement in three other patients. All of these patients had abnormal CSF analyses. In two of the three cases of abnormal leptomeningeal enhancement the disease was more evident on high-dose than on standard-dose imaging; in one case the abnormal enhancement was visible only on high-dose imaging. In one of the three cases with abnormal pachymeningeal enhancement, the disease was evident prospectively only with high-dose imaging. (orig.)

  13. Endoluminal high dose rate brachytherapy in the treatment of primary and recurrent bronchogenic tree malignancies

    Directory of Open Access Journals (Sweden)

    Maria Fortunato

    2009-03-01

    Full Text Available Introduction: Locally advanced tumours as the initial form of presentation of tumours in the bronchial tree are not a rare event. Bronchogenic recurrence is frequent in the natural history of some tumours. The choice of therapeutic options from the raft available depends on such variables as initial therapy, place of recurrence, symptoms and patient's physical status. Aim: To demonstrate the advantages of endoluminal brachytherapy (EBT with high dose rate (HDR in primary and recurrent tumour of the bronchial tree. Material and methods: A retrospective study of seven patients (pts with primary tumours of the colon, trachea and lung. Tracheobronchial recurrence (trachea, two pts, bronchus, five pts occurred betweenMarch 2003 and September 2004. Patients under-went EBT with HDR for primary or recurrent therapy in association with external radiotherapy, laser therapy and chemotherapy with palliative or curative intention. EBT with HDR doses of 5 to 7 Gy in 2 to 4 fractions at 1 cm from the source axis were given. Treatment included endoluminal application of Ir192 with a French 6 catheter. Results: There was symptomatic relief related to reduction of tumour in six of the seven patients treated. In one of the six patients studied, there was progression of the local disease between the second and third fractions of the treatment (obstruction of the trachea. In a mean follow up of 17 (2-40 months between EBT and this study, three patients are alive, one has no evidence of disease while two have had bronchial recurrence, four patients have died, one after massive haemoptysis and three due to disease progression. Discussion and conclusions: Patients undergoing brachytherapy for symptomatic primary tumours or endobronchial recurrence show good tolerance, important symptom relief and improved quality of life. Despite the small size of our sample, it is clear that EBT with HDR plays an important role in the palliative/curative treatment of these patients

  14. Results in patients treated with high-dose-rate interstitial brachytherapy for oral tongue cancer

    International Nuclear Information System (INIS)

    Yamamoto, Michinori; Shirane, Makoto; Ueda, Tsutomu; Miyahara, Nobuyuki

    2006-01-01

    Eight patients were treated with high-dose-rate interstitial brachytherapy for oral tongue cancer between September 2000 and August 2004. The patient distribution was 1 T1, 5 T2, 1 T3, and 1 T4a. Patients received 50-60 Gy in 10 fractions over seven days with high-dose-rate brachytherapy. Six of the eight patients were treated with a combination of external beam radiotherapy (20-30 Gy) and interstitial brachytherapy. The two-year primary local control rate was 83% for initial case. High-dose-rate brachytherapy was performed safely even for an aged person, and was a useful treatment modality for oral tongue cancer. (author)

  15. High dose therapy with autologous stem cell support in malignant disorders

    International Nuclear Information System (INIS)

    Holte, H.; Kvaloey, S.O.; Engan, T.

    1996-01-01

    New biomedical knowledge may improve the diagnostic procedures and treatment provided by the Health Services, but at additional cost. In a social democratic health care system, the hospital budgets have no room for expensive, new procedures or treatments, unless these are funded through extra allocation from the central authorities. High dose therapy with autologous stem cell support in malignant disorders is an example of a new and promising, but rather expensive treatment, but its role in cancer therapy has yet to be established. The indications for testing high dose therapy with autologous stem cell support in various malignancies are discussed, with emphasis on the principles for deciding which categories of disease should have priority. The authors suggest some malignant disorder for which high dose therapy with stem cell support should be explored versus conventional treatment in randomized prospective trials. 8 refs., 1 tab

  16. Plasma Doping - Enabling Technology for High Dose Logic and Memory Applications

    International Nuclear Information System (INIS)

    Miller, T.; Godet, L.; Papasouliotis, G. D.; Singh, V.

    2008-01-01

    As logic and memory device dimensions shrink with each generation, there are more high dose implants at lower energies. Examples include dual poly gate (also referred to as counter-doped poly), elevated source drain and contact plug implants. Plasma Doping technology throughput and dopant profile benefits at these ultra high dose and lower energy conditions have been well established [1,2,3]. For the first time a production-worthy plasma doping implanter, the VIISta PLAD tool, has been developed with unique architecture suited for precise and repeatable dopant placement. Critical elements of the architecture include pulsed DC wafer bias, closed-loop dosimetry and a uniform low energy, high density plasma source. In this paper key performance metrics such as dose uniformity, dose repeatability and dopant profile control will be presented that demonstrate the production-worthiness of the VIISta PLAD tool for several high dose applications.

  17. Administration of Concurrent Vaginal Brachytherapy During Chemotherapy for Treatment of Endometrial Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nagar, Himanshu; Boothe, Dustin; Parikh, Amar; Yondorf, Menachem; Parashar, Bhupesh [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Gupta, Divya; Holcomb, Kevin; Caputo, Thomas [Division of Gynecological Oncology, Department of Obstetrics and Gynecology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Chao, K. S. Clifford; Nori, Dattatreyudu [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Wernicke, A. Gabriella, E-mail: gaw9006@med.cornell.edu [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States)

    2013-11-15

    Purpose: To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. Methods and Materials: A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB + external beam RT (EBRT) + 6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. Results: Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P<.001; 95% confidence interval: 3.99-4.02) and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities in comparison with the patients treated with VB and chemotherapy in a sequential manner (P>.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. Conclusions: VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen.

  18. Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial.

    Science.gov (United States)

    Strain, E C; Bigelow, G E; Liebson, I A; Stitzer, M L

    1999-03-17

    Methadone hydrochloride treatment is the most common pharmacological intervention for opioid dependence, and recent interest has focused on expanding methadone treatment availability beyond traditional specially licensed clinics. However, despite recommendations regarding effective dosing of methadone, controlled clinical trials of higher-dose methadone have not been conducted. To compare the relative clinical efficacy of moderate- vs high-dose methadone in the treatment of opioid dependence. A 40-week randomized, double-blind clinical trial starting in June 1992 and ending in October 1995. Outpatient substance abuse treatment research clinic at the Johns Hopkins University Bayview Campus, Baltimore, Md. One hundred ninety-two eligible clinic patients. Daily oral methadone hydrochloride in the dose range of 40 to 50 mg (n = 97) or 80 to 100 mg (n = 95), with concurrent substance abuse counseling. Opioid-positive urinalysis results and retention in treatment. By intent-to-treat analysis through week 30 patients in the high-dose group had significantly lower rates of opioid-positive urine samples compared with patients in the moderate-dose group (53.0% [95% confidence interval [CI], 46.9%-59.2%] vs 61.9% [95% CI, 55.9%-68.0%]; P = .047. These differences persisted during withdrawal from methadone. Through day 210 no significant difference was evident between dose groups in treatment retention (high-dose group mean retention, 159 days; moderate-dose group mean retention, 157 days). Nineteen (33%) of 57 patients in the high-dose group and 11 (20%) of 54 patients in the moderate-dose group completed detoxification. Both moderate- and high-dose methadone treatment resulted in decreased illicit opioid use during methadone maintenance and detoxification. The high-dose group had significantly greater decreases in illicit opioid use.

  19. Experimental research on fresh mussel meat irradiated by high-dose electron beam

    International Nuclear Information System (INIS)

    Xiao Lin; Lu Ruifeng; Hu Huachao; Wang Chaoqi; Liu Yanna

    2011-01-01

    The sterilization storage of fresh mussel irradiated high-dose electron beam was studied. From the subjective assessment by the weighted average of the test and other determined parameters, it can be concluded that the flavor of fresh mussel meat sealed canned food irradiated by high-dose electron beam has not been significant affected, and various micro-organisms can be killed effectively, which means that the irradiated fresh mussel meat can be preserved for long-term at room temperature. Therefore the method might resolve the problems induced by traditional frozen preservation methods. (authors)

  20. Statistical behavior of high doses in medical radiodiagnosis; Comportamento estatistico das altas doses em radiodiagnostico medico

    Energy Technology Data Exchange (ETDEWEB)

    Barboza, Adriana Elisa, E-mail: adrianaebarboza@gmail.com, E-mail: elisa@bolsista.ird.gov.br [Instituto de Radioprotecao e Dosimetria, (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2014-07-01

    This work has as main purpose statistically estimating occupational exposure in medical diagnostic radiology in cases of high doses recorded in 2011 at national level. For statistical survey of this study, doses of 372 IOE's diagnostic radiology in different Brazilian states were evaluated. Data were extracted from the work of monograph (Research Methodology Of High Doses In Medical Radiodiagnostic) that contains the database's information Sector Management doses of IRD/CNEN-RJ, Brazil. The identification of these states allows the Sanitary Surveillance (VISA) responsible, becomes aware of events and work with programs to reduce these events. (author)

  1. [High-dosed gestagen therapy of the metastatic mammary carcinoma (author's transl)].

    Science.gov (United States)

    Firusian, N; Becher, R

    1981-12-01

    Thirty patients with histologically proven metastatic mammary carcinoma were treated, after exhaustion of hormonal and cytostatic therapeutic means, with high-dosed medroxyprogesterone acetate (MPA) during a ten-day induction phase with 1000 mg MPAi.m. per day and then with 600 mg oral MPA per day. In eleven patients a complete or partial remission was achieved. The median period of remission comprised ten months. A positive relationship was found between the response to high-dosed MPA therapy and the length of free intervals. Side effects were tolerable.

  2. Analysis of volatile organic compounds and sensory characteristics of pork loin samples irradiated to high doses

    International Nuclear Information System (INIS)

    Hou Zhengchi; Sun Dakuan; Qin Zongying; Jin Jiang; Zhu Liandi; Yao Side; Sheng Kanglong

    2005-01-01

    Fresh pork loin samples, protein enzyme inactivated at (72 ± 3) degree C and vacuum packaged, were irradiated to up to 45 kGy at -20 degree C by 60 Co γ-rays. The irradiated samples were examined by various kinds of method to study high dose irradiation effects of sensory changes (meat color and off-odor), transverse shearing strength, weight loss in steam cooking, volatile organic compounds, and lipid oxidation. The results showed that the high dose irradiation produced no serious effects to the pork loin samples, and volunteer responses showed fine acceptability to the irradiated meat. (authors)

  3. Evaluation of glasses containing cadmium for high dose dosimetry by the thermoluminescence technique

    International Nuclear Information System (INIS)

    Carvalho, Gabriel Soares Marchiori de; Ferreira, Pamela Zati; Cunha, Diego Merigue da; Dantas, Noelio Oliveira; Silva, Anielle C.A.; Perini, Ana Paula; Neves, Lucio Pereira; Carrera, Betzabel Noemi Silva; Watanabe, Shigueo

    2016-01-01

    New glass matrices were evaluated for high dose dosimetry by the thermoluminescence technique. Their nominal composition are 20Li_2CO_3.10Al_2O_3.15CdO.55B_2O_3 and 20Li_2CO_3.10Al_2O_3.20CdO.50B_2O_3 (mol%). The glass matrices were irradiated with different doses: 50, 100, 200, 500, 700 and 900 Gy, and the thermoluminescence emission curves were obtained for each of these values. The results show a great potential of using these matrices in high dose dosimetry. (author)

  4. Salvage high-dose-rate brachytherapy for local prostate cancer recurrence after radical radiotherapy

    Directory of Open Access Journals (Sweden)

    V. A. Solodkiy

    2016-01-01

    Full Text Available Studies salvage interstitial radiation therapy for recurrent prostate cancer, launched at the end of the XX century. In recent years, more and more attention is paid to high-dose-rate brachytherapy (HDR-BT as a method of treating local recurrence.The purpose of research – preliminary clinical results of salvage high-dose-rate brachytherapy applied in cases of suspected local recurrence or of residual tumour after radiotherapy.Preliminary findings indicate the possibility of using HDR-BT, achieving local tumor control with low genitourinary toxicity.

  5. Early infections in patients undergoing high-dose treatment with stem cell support: a comparison of patients with non-Hodgkin lymphoma and multiple myeloma

    DEFF Research Database (Denmark)

    Gang, A O; Arpi, M.; Gang, U.J.O.

    2010-01-01

    Background: Infections are life-threatening complications in patients undergoing high-dose chemotherapy with stem cell support (HDT). Knowledge of the infectious pathogens is essential to make a safe outpatient setting. Methods: We conducted a retrospective study of 208 patients treated with HDT...... related mortality was similar between the groups. Conclusion: The frequency of isolated pathogens, positive blood cultures, and the diversity of pathogens were higher in MM patients as compared to NHL patients. However, this did not translate into higher transplantation-related mortality, probably because....... The population included non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) patients. No patients received prophylactic antibacterial treatment. Results: Pathogens were isolated from 44% of all patients. MM patients more frequently had multiple pathogens in blood cultures (38% versus 25%). Transplantation...

  6. High-dose melphalan and autologous stem cell transplantation for AL amyloidosis: recent trends in treatment-related mortality and 1-year survival at a single institution

    Science.gov (United States)

    Seldin, D. C.; Andrea, N.; Berenbaum, I.; Berk, J. L.; Connors, L.; Dember, L. M.; Doros, G.; Fennessey, S.; Finn, K.; Girnius, S.; Lerner, A.; Libbey, C.; Meier-Ewert, H. K.; O’Connell, R.; O’Hara, C.; Quillen, K.; Ruberg, F. L.; Sam, F.; Segal, A.; Shelton, A.; Skinner, M.; Sloan, J. M.; Wiesman, J. F.; Sanchorawala, V.

    2017-01-01

    Treatment with high-dose melphalan chemotherapy supported by hematopoietic rescue with autologous stem cells produces high rates of hematologic responses and improvement in survival and organ function for patients with AL amyloidosis. Ongoing clinical trials explore pre-transplant induction regimens, post-transplant consolidation or maintenance approaches, and compare transplant to non-transplant regimens. To put these studies into context, we reviewed our recent experience with transplant for AL amyloidosis in the Amyloid Treatment and Research Program at Boston Medical Center and Boston University School of Medicine. Over the past 10 years, there was a steady reduction in rates of treatment-related mortality and improvement in 1-year survival, now approximately 5% and 90%, respectively, based upon an intention-to-treat analysis. Median overall survival of patients treated with this approach at our center exceeds 7.5 years. PMID:21838459

  7. Use of maintenance endocrine therapy after chemotherapy in metastatic breast cancer.

    Science.gov (United States)

    Sutherland, S; Miles, D; Makris, A

    2016-12-01

    For women with oestrogen receptor+ metastatic breast cancer (MBC), the options for systemic treatment include endocrine therapy (ET) and chemotherapy. For women whose disease is also HER2+, anti-HER2 therapies are also routinely used either with chemotherapy or less commonly with ET. Where chemotherapy is used as initial therapy, treatment is often discontinued due to cumulative toxicity in the absence of disease progression. In this setting, there is the option of introducing ET with the aim of prolonging response and delaying relapse. Literature review revealed four trials addressing the question of whether there is a benefit from introducing ET following chemotherapy for MBC. We also sought evidence for alternative approaches, including concurrent chemotherapy and ET and continuing chemotherapy until disease progression. The evidence for the use of ET after chemotherapy in MBC is limited, and the trials done were small. Furthermore, they were performed at a time when both the chemotherapy regimens and ET were different from those used currently. Despite these limitations, there is probably a modest improvement in time to progression for the sequential use of ET after chemotherapy but with no overall survival benefit. An alternative approach, particularly considering agents with relatively low toxicity, such as orally bioavailable fluoropyrimidines, is to continue chemotherapy until disease progression. Where chemotherapy for MBC is discontinued due to toxicity, in the absence of progression, the use of ET, with its relatively low toxicity, is a reasonable approach with the aim of delaying relapse. Copyright © 2016. Published by Elsevier Ltd.

  8. Efficacy and tolerability of high dose "ethinylestradiol" in post-menopausal advanced breast cancer patients heavily pre-treated with endocrine agents.

    Science.gov (United States)

    Agrawal, Amit; Robertson, John F R; Cheung, K L

    2006-07-11

    High dose estrogens (HDEs) were frequently used as endocrine agents prior to the introduction of tamoxifen which carries fewer side effects. Due to the development of resistance to available endocrine agents in almost all women with metastatic breast cancer, interest has renewed in the use of HDEs as yet another endocrine option that may have activity. We report our experience with one of the HDEs ("ethinylestradiol" 1 mg daily) in advanced breast cancer (locally advanced and metastatic) in post-menopausal women who had progressed on multiple endocrine agents. According to a database of advanced breast cancer patients seen in our Unit since 1998, those who had complete set of information and fulfilled the following criteria were studied: (1) patients in whom further endocrine therapy was deemed appropriate i.e., patients who have had clinical benefit with previous endocrine agents or were not fit or unwilling to receive chemotherapy in the presence of potentially life-threatening visceral metastases; (2) disease was assessable by UICC criteria; (3) were treated with "ethinylestradiol" until they were withdrawn from treatment due to adverse events or disease progression. Twelve patients with a median age of 75.1 years (49.1-85 years) were identified. Majority (N = 8) had bony disease. They had ethinylestradiol as 3rd to 7th line endocrine therapy. One patient (8%) came off treatment early due to hepato-renal syndrome. Clinical benefit (objective response or durable stable disease for > or = 6 months) was seen in 4 patients (33.3%) with a median duration of response of 10+ (7-36) months. The time to treatment failure was 4 (0.5-36) months. Yet unreported, high dose "ethinylestradiol" is another viable therapeutic strategy in heavily pre-treated patients when further endocrine therapy is deemed appropriate. Although it tends to carry more side effects, they may not be comparable to those of other HDEs (such as diethylstilbestrol) or chemotherapy.

  9. High-dose metoclopramide + lorazepam versus low-dose metoclopramide + lorazepam + dehydrobenzperidol in the treatment of cisplatin-induced nausea and vomiting

    DEFF Research Database (Denmark)

    Herrstedt, Jørn; Hannibal, J; Hallas, Jesper

    1991-01-01

    In a randomized double-blind, cross-over trial of 34 patients receiving cisplatin-based chemotherapy (20-100 mg/m2), the antiemetic effect of high-dose metoclopramide (HDM) (10 mg/kg iv. loading dose + 7 hours continuous infusion) + lorazepam (L) (2.5 mg x 4 po) was compared with low......-dose metoclopramide (LDM) (70 mg) + L (2.5 mg x 2 po) + dehydrobenzperidol (5 mg x 2 im). Among the 29 patients who completed the cross-over, HDM significantly reduced the number of vomiting episodes (p = 0.002) and the degree of nausea (p = 0.004). Seventeen patients preferred the HDM and 4 the LDM regimen (p = 0.......01). Sedation was seen in all but 1 patient, and was graded as severe in 6 patients receiving the HDM and in 2 patients receiving the LDM regimen. No extrapyramidal adverse reactions were seen. We conclude that high-dose metoclopramide + lorazepam is a safe antiemetic regimen and significantly superior to low...

  10. A Phase I Study of Pulse High-Dose Vorinostat (V) plus Rituximab (R), Ifosphamide, Carboplatin, and Etoposide (ICE) in Patients with Relapsed Lymphoma

    Science.gov (United States)

    Budde, Lihua E.; Zhang, Michelle M.; Shustov, Andrei R.; Pagel, John M.; Gooley, Ted A.; Oliveira, George R.; Chen, Tara L.; Knudsen, Nancy L.; Roden, Jennifer E.; Kammerer, Britt E.; Frayo, Shani L.; Warr, Thomas A.; Boyd, Thomas E.; Press, Oliver W.; Gopal, Ajay K.

    2013-01-01

    SUMMARY Given the poor outcomes of relapsed aggressive lymphomas and preclinical data suggesting that ≥2.5 μM concentrations of vorinostat synergize with both etoposide and platinums, we hypothesized that pulse high-dose vorinostat could safely augment the anti-tumour activity of (R)ICE [(rituximab), ifosphamide, carboplatin, etoposide] chemotherapy. We conducted a phase I dose escalation study using a schedule with oral vorinostat ranging from 400 mg/d to 700 mg bid for 5 days in combination with the standard (R)ICE regimen (days 3, 4 and 5). Twenty-nine patients (median age 56 years, median 2 prior therapies, 14 chemoresistant [of 27 evaluable], 2 prior transplants) were enrolled and treated. The maximally tolerated vorinostat dose was defined as 500 mg twice daily × 5 days. Common dose limiting toxicities included infection (n=2), hypokalaemia (n=2), and transaminitis (n=2). Grade 3 related gastrointestinal toxicity was seen in 9 patients. The median vorinostat concentration on day 3 was 4.5 μM (range 4.2–6.0 μM) and in vitro data confirmed the augmented antitumour and histone acetylation activity at these levels. Responses were observed in 19 of 27 evaluable patients (70%) including 8 complete response/unconfirmed complete response. High-dose vorinostat can be delivered safely with (R)ICE, achieves potentially synergistic drug levels, and warrants further study, although adequate gastrointestinal prophylaxis is warranted. PMID:23356514

  11. Daily high doses of fluoxetine for weight loss and improvement in lifestyle before bariatric surgery

    NARCIS (Netherlands)

    Dolfing, JG; Wolffenbuttel, BHR; Oei, HI; ten Hoor-Aukerna, NM; Schweitzer, DH

    Background: The number of gastric restrictive bariatric operations is increasing each year, but about one-fifth of patients will become disappointed due to unsatisfactory weight reduction or annoying complications. We questioned whether weight reduction by taking high doses of fluoxetine improves

  12. Fertility of Tall Girls Treated with High-Dose Estrogen, a Dose-Response Relationship

    NARCIS (Netherlands)

    Hendriks, A. E. J.; Drop, S. L. S.; Laven, J. S. E.; Boot, A. M.

    Context: High-dose estrogen treatment to reduce final height of tall girls increases their risk for infertility in later life. Objective: The aim was to study the effect of estrogen dose on fertility outcome of these women. Design/Setting: We conducted a retrospective cohort study of university

  13. Differential sensitivity of long-sleep and short-sleep mice to high doses of cocaine.

    Science.gov (United States)

    de Fiebre, C M; Ruth, J A; Collins, A C

    1989-12-01

    The cocaine sensitivity of male and female long-sleep (LS) and short-sleep (SS) mice, which have been selectively bred for differential ethanol-induced "sleep-time," was examined in a battery of behavioral and physiological tests. Differences between these two mouse lines were subtle and were seen primarily at high doses. At high doses, SS mice were more sensitive than LS mice, particularly to cocaine-induced hypothermia; however, significant hypothermia was not seen except at doses which were very near to the seizure threshold. During a 60-min test of locomotor activity, LS mice showed greater stimulation of Y-maze activity by 20 mg/kg cocaine than SS mice. Consistent with the finding of subtle differences in sensitivity to low doses of cocaine. LS and SS mice did not differ in sensitivity to cocaine inhibition of synaptosomal uptake of [3H]-dopamine, [3H]-norepinephrine or [3H]-5-hydroxytryptamine. However, consistent with the finding of differential sensitivity to high doses of cocaine, SS mice were more sensitive to the seizure-producing effects of the cocaine and lidocaine, a local anesthetic. It is hypothesized that the differential sensitivity of these mouse lines to high doses of cocaine is due to differential sensitivity to cocaine's actions on systems that regulate local anesthetic effects. Selective breeding for differential duration of alcohol-induced "sleep-time" may have resulted in differential ion channel structure or function in these mice.

  14. Perennial soybean seeds coated with high doses of boron and zinc ...

    African Journals Online (AJOL)

    The objective of this work was to study combinations of high doses of boron (B) and zinc (Zn) in the recoating of perennial soybean seeds, in order to provide these nutrients to the future plants. The physical, physiological and nutritional characteristics of the coated seeds and initial development of plants in a greenhouse ...

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

    Directory of Open Access Journals (Sweden)

    F. A. Zeiler

    2015-01-01

    Full Text Available 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.

  16. Quantitative MR changes in Gd-DTPA enhancement after high dose intravenous methylprednisolone in multiple sclerosis

    International Nuclear Information System (INIS)

    Barkhof, F.; Valk, J.; Hommes, O.R.; Scheltens, P.

    1991-01-01

    The purpose of this study was to investigate the effect of high dose intravenous methylprednisolone (MP) on gadolinium-DTPA enhancement in MS-lesions. By means of this the influence of MP on the permeability of the blood-brain barrier can be studied. (author). 19 refs.; 1 fig

  17. Irreversible neurological worsening following high-dose corticosteroids in advanced progressive multiple sclerosis

    NARCIS (Netherlands)

    Koch, M; De Keyser, J

    2006-01-01

    Background: A course of high-dose corticosteroids has been shown to hasten recovery from a relapse of multiple sclerosis (MS). Some patients with progressive MS ask for a course with corticosteroids outside a relapse, hoping to gain some functional improvement. Objective: To describe 4 patients with

  18. Cytoprotective responses in HaCaT keratinocytes exposed to high doses of curcumin

    NARCIS (Netherlands)

    Lundvig, D.M.S.; Pennings, S.W.C.; Brouwer, K.M.; Mtaya-Mlangwa, M.; Mugonzibwa, E.; Kuijpers-Jagtman, A.M.; Wagener, F.A.D.T.G.; Hoff, J.W. Von den

    2015-01-01

    Wound healing is a complex process that involves the well-coordinated interactions of different cell types. Topical application of high doses of curcumin, a plant-derived polyphenol, enhances both normal and diabetic cutaneous wound healing in rodents. For optimal tissue repair interactions between

  19. Absorption of high-dose enteral vitamin A in lowbirth- weight neonates

    African Journals Online (AJOL)

    A randomised, double-blind placebo-controlled trial was designed to detennine whether high-dose (25 000 IU) enteral vitamin A. to correct deficiency, would be absorbed and well tolerated in low-birth-weight (LBW) neonates. Thirty-five LBW infants (950 - 1 700 g; gestational age 27 - 36 weeks) were allocated to receive ...

  20. Surface damage of 316 stainless steel irradiated with 4He+ to high doses

    International Nuclear Information System (INIS)

    Kaminsky, M.; Das, S.K.

    1978-01-01

    Surface blistering of niobium by implantation with helium ions in the 9 to 15 keV range was investigated. The apparent disappearance of blisters at sufficiently high doses was believed to be an equilibrium effect. To determine whether high temperature annealing causes the equilibrium condition, stainless steel-316 samples were irradiated at a constant 450 0 C. Results are presented

  1. Perioperative Interstitial High-Dose-Rate Brachytherapy for the Treatment of Recurrent Keloids

    DEFF Research Database (Denmark)

    Jiang, Ping; Baumann, René; Dunst, Jürgen

    2016-01-01

    PURPOSE: To prospectively evaluate high-dose-rate brachytherapy in the treatment of therapy-resistant keloids and report first results, with emphasis on feasibility and early treatment outcome. METHODS AND MATERIALS: From 2009 to 2014, 24 patients with 32 recurrent keloids were treated with immed...

  2. Influence of high doses of manganese, copper, zinc and boron on some legumes

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, G

    1973-01-01

    Macroscopic and microscopic examinations showed the following symptoms of an excess in trace elements: (1) High doses of manganese (50-150 ppm) cause dark patches (chloroplast accumulation) in young leaves, and necrosis of the leaf margin (MnO/sub 2/ accumulation) in older leaves. The roots become brown and die off. Roots newly formed in compensation are strikingly light-colored. (2) High doses of copper (5-40 ppm) cause iron deficiency chlorosis. A large number of side roots develop in quick succession as a result of damage to the root apex, so that a thick tangle of roots is formed. (3) High doses of zinc (50-150 ppm) bring about dark green, very brittle young leaves with very high ZnO content. The older leaves become red and then yellow. The roots remain stunted because of inhibited growth in length. (4) High doses of boron (30-90 ppm) cause a leaf necrosis which proceeds in the sequence tip, margin, lamina. The roots are not affected in any characteristic way. They become brown and die off.

  3. Determination of air kerma standard of high dose rate 192Ir brachytherapy source

    International Nuclear Information System (INIS)

    Pires, E.J.; Alves, C.F.E.; Leite, S.P.; Magalhaes, L.A.G.; David, M.G.; Almeida, C.E. de

    2015-01-01

    This paper presents the methodology developed by the Laboratorio de Ciencias Radiologicas and presently in use for determining of the air kerma standard of 192 Ir high dose rate sources to calibrate well-type chambers. Uncertainty analysis involving the measurements procedure are presented. (author)

  4. Hemolytic anemia following high dose intravenous immunoglobulin in patients with chronic neurological disorders

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Christiansen, I; Harbo, Thomas

    2014-01-01

    High dose intravenous immunoglobulin (IVIG) is an established treatment for various neuromuscular disorders. Recently, cases of hemolytic anemia following IVIG have been observed. The objective of this study was to determine the extent of anemia and hemolysis after IVIG and its relationship...

  5. High-dose therapy followed by bone marrow transplantation for relapsed follicular non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Schouten, IC; Raemaekers, JJM; Kluin-Nelemans, HC; vanKamp, H; Mellink, WAM; vantVeer, MB

    1996-01-01

    Purpose: To analyze whether, in addition to survival, and disease-free survival progression-free interval after transplantation would be longer than the last progression-free interval before transplantation, supporting the argument that high-dose therapy may change the biologic behavior of the

  6. Maternal high-dose folic acid during pregnancy and asthma medication in the offspring

    NARCIS (Netherlands)

    Zetstra-van der Woude, Priscilla A.; De Walle, Hermien E. K.; Hoek, Annemieke; Bos, H. Jens; Boezen, H. Marike; Koppelman, Gerhard H.; de Jong-van den Berg, Lolkje T. W.; Scholtens, Salome

    2014-01-01

    Purpose Low-dose folic acid supplementation (0.5 mg) taken during pregnancy has been associated with an increased risk for childhood asthma. The effect of high-dose folic acid (5 mg) advised to women at risk for having a child with neural tube defect has not been assessed so far. Our aim was to

  7. Occlusion-amblyopia following high dose oral levodopa combined with part time patching

    OpenAIRE

    Mihir Kothari

    2014-01-01

    Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  8. Occlusion-amblyopia following high dose oral levodopa combined with part time patching.

    Science.gov (United States)

    Kothari, Mihir

    2014-12-01

    Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  9. Occlusion-amblyopia following high dose oral levodopa combined with part time patching

    Directory of Open Access Journals (Sweden)

    Mihir Kothari

    2014-01-01

    Full Text Available Part time occlusion therapy is not reported to cause occlusion (reverse amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  10. High Dose Ascorbate Causes Both Genotoxic and Metabolic Stress in Glioma Cells

    Science.gov (United States)

    Castro, Maria Leticia; Carson, Georgia M.; McConnell, Melanie J.; Herst, Patries M.

    2017-01-01

    We have previously shown that exposure to high dose ascorbate causes double stranded breaks (DSBs) and a build-up in S-phase in glioblastoma (GBM) cell lines. Here we investigated whether or not this was due to genotoxic stress as well as metabolic stress generated by exposure to high dose ascorbate, radiation, ascorbate plus radiation and H2O2 in established and primary GBM cell lines. Genotoxic stress was measured as phosphorylation of the variant histone protein, H2AX, 8-oxo-7,8-dihydroguanine (8OH-dG) positive cells and cells with comet tails. Metabolic stress was measured as a decrease in NADH flux, mitochondrial membrane potential (by CMXRos), ATP levels (by ATP luminescence) and mitochondrial superoxide production (by mitoSOX). High dose ascorbate, ascorbate plus radiation, and H2O2 treatments induced both genotoxic and metabolic stress. Exposure to high dose ascorbate blocked DNA synthesis in both DNA damaged and undamaged cell of ascorbate sensitive GBM cell lines. H2O2 treatment blocked DNA synthesis in all cell lines with and without DNA damage. DNA synthesis arrest in cells with damaged DNA is likely due to both genotoxic and metabolic stress. However, arrest in DNA synthesis in cells with undamaged DNA is likely due to oxidative damage to components of the mitochondrial energy metabolism pathway. PMID:28737676

  11. Diagnosis of cerebral metastases by means of standard doses of Gadobutrol versus a high-dose protocol. Intraindividual evaluation of a phase-II high-dose study

    International Nuclear Information System (INIS)

    Vogl, T.J.; Friebe, C.E.; Balzer, T.; Mack, M.G.; Steiner, S.; Schedel, H.; Pegios, W.; Lanksch, W.; Banzer, D.; Felix, R.

    1995-01-01

    In a clinical phase-II study 20 patients who had been diagnosed as having brain metastases with CT or MRT were studied prospectively with Gadobutrol, a new nonionic, low osmolality contrast agent. Each patient received an initial injection of 0.1 mmol/kg body weight and an additional dose of 0.2 mmol/kg Gadobutrol 10 min later. Spinecho images were obtained before and after the two applications of Gadobutrol. Dynamic scanning (Turbo-FLASH) was performed for 3 min after each injection of the contrast agent. Both quantitative and qualitative data were intraindividually evaluated. The primary tumor was a bronchial carcinoma in 11 cases; in 9 other cases there were different primary tumors. Forty-eight hours after the use of Gadobutrol there were no adverse signs in the clinical examination, vital signs or blood and urine chemistry. Statistical analysis (Friedman test and Wilcoxon test) of the C/N ratios between tumor and white matter, percentage enhancement, and visual assessment rating revealed statistically significant superiority of high-dose Gadobutrol injection in comparison to the standard dose. The percentage enhancement increased on average from 104% after 0.1 mmol/kg to 162% after 0.3 mmol/kg Gadobutrol. Qualitative delineation and contrast of the lesions increased significantly. The use of high-dose Gadobutrol improved the detection of 36 additional lesions in 6 patients. (orig./VHE) [de

  12. Chemotherapy in eye cancer

    African Journals Online (AJOL)

    is a drug used in a wide range of cancers, which produces ... lesions. In a 10-year retrospective review of .... disease and focal chemotherapy for selected high-risk ... of focal drug delivery methods to reduce recurrence .... the protein tubulin.

  13. Prevent Infections During Chemotherapy

    Centers for Disease Control (CDC) Podcasts

    This podcast discusses the importance of preventing infections in cancer patients who are undergoing chemotherapy. Dr. Lisa Richardson, CDC oncologist, talks about a new Web site for cancer patients and their caregivers.

  14. MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells.

    Directory of Open Access Journals (Sweden)

    Thomas Walenda

    Full Text Available Hematopoietic regeneration after high dose chemotherapy necessitates activation of the stem cell pool. There is evidence that serum taken after chemotherapy comprises factors stimulating proliferation and self-renewal of CD34(+ hematopoietic stem and progenitor cells (HSPCs--however, the nature of these feedback signals is yet unclear. Here, we addressed the question if specific microRNAs (miRNAs or metabolites are affected after high dose chemotherapy. Serum taken from the same patients before and after chemotherapy was supplemented for in vitro cultivation of HSPCs. Serum taken after chemotherapy significantly enhanced HSPC proliferation, better maintained a CD34(+ immunophenotype, and stimulated colony forming units. Microarray analysis revealed that 23 miRNAs changed in serum after chemotherapy--particularly, miRNA-320c and miRNA-1275 were down-regulated whereas miRNA-3663-3p was up-regulated. miRNA-320c was exemplarily inhibited by an antagomiR, which seemed to increase proliferation. Metabolomic profiling demonstrated that 44 metabolites were less abundant, whereas three (including 2-hydroxybutyrate and taurocholenate sulphate increased in serum upon chemotherapy. Nine of these metabolites were subsequently tested for effects on HSPCs in vitro, but none of them exerted a clear concentration dependent effect on proliferation, immunophenotype and colony forming unit formation. Taken together, serum profiles of miRNAs and metabolites changed after chemotherapy. Rather than individually, these factors may act in concert to recruit HSPCs into action for hematopoietic regeneration.

  15. Hypertonic saline solution and high-dose furosemide infusion in cardiorenal syndrome: our experience

    Directory of Open Access Journals (Sweden)

    Francesco Ventrella

    2013-03-01

    Full Text Available Introduction Heart failure is frequently complicated by renal failure, and this association is a negative prognostic factor. These patients sometimes present oligo-/anuria and resistance to high-dose furosemide, a condition referred to as the cardiorenal syndrome (CRS. Acute or chronic reductions in left ventricular function result in decreased blood flow, with reduction of renal perfusion and activation of several neurohormonal systems, which cause resistance to diuretic therapy. This condition often requires ultrafiltration, which is an effective, but invasive and expensive procedure. Infusions of hypertonic saline solution (HSS and high-dose furosemide can be an effective alternative. Materials and methods From November 2009 through May 2010, our team treated 20 patients with CRS and resistance to iv boluses of high-dose furosemide. These patients were treated with small-volume (150-250 mL infusions of HSS (NaCl 1.57 – 4.5%, depending on serum Na values and high-dose furosemide twice a day. The aim of this treatment is to modify renal hemodynamics and the water-saline balance in the kidney by counteracting the extracellular fluid accumulation and eliminating symptoms of congestion. Results In 18 patients (90%, urine output was restored and renal function improved during the first hours of treatment. Clinical improvement was evident from the first day of therapy, and there were no adverse events. Two patients (10% did not respond to the treatment: one (who had been in critical condition since admission died; the other required regular sessions of ultrafiltration. Conclusions HSS combined with high-dose furosemide is a safe, effective, low-cost approach to the treatment of CRS that is resistant to diuretic therapy.

  16. Review of high-dose intravenous vitamin C as an anticancer agent.

    Science.gov (United States)

    Wilson, Michelle K; Baguley, Bruce C; Wall, Clare; Jameson, Michael B; Findlay, Michael P

    2014-03-01

    In the 1970s, Pauling and Cameron reported increased survival of patients with advanced cancer treated with high-dose intravenous (IV) vitamin C (L-ascorbate, ascorbic acid). These studies were criticized for their retrospective nature and lack of standardization of key prognostic factors including performance status. Subsequently, several well-designed randomized controlled trials failed to demonstrate a significant survival benefit, although these trials used high-dose oral vitamin C. Marked differences are now recognized in the pharmacokinetics of vitamin C with oral and IV administration, opening the issue of therapeutic efficacy to question. In vitro evidence suggests that vitamin C functions at low concentrations as an antioxidant but may have pro-oxidant activity at high concentrations. The mechanism of its pro-oxidant action is not fully understood, and both intra- and extracellular mechanisms that generate hydrogen peroxide have been proposed. It remains to be proven whether vitamin C-induced reactive oxygen species occur in vivo and, if so, whether this will translate to a clinical benefit. Current clinical evidence for a therapeutic effect of high-dose IV vitamin C is ambiguous, being based on case series. The interpretation and validation of these studies is hindered by limited correlation of plasma vitamin C concentrations with response. The methodology exists to determine if there is a role for high-dose IV vitamin C in the treatment of cancer, but the limited understanding of its pharmacodynamic properties makes this challenging. Currently, the use of high-dose IV vitamin C cannot be recommended outside of a clinical trial. © 2014 Wiley Publishing Asia Pty Ltd.

  17. High Dose Oral Calcium Treatment in Patients with Vitamin D-dependent Rickets Type II

    Directory of Open Access Journals (Sweden)

    R Vakili

    2017-02-01

    Full Text Available BACKGROUND AND OBJECTIVE: Vitamin D-dependent rickets type II (VDDR2 is a rare genetic disorder caused by mutations in vitamin D receptor (VDR and leads to resistance to biological effects of calcitriol. Based on the type of mutation, this disease is resistant to calcitriol even at high doses of calcitriol and successful treatment of these patients requires hypocalcemic modification through administration of high doses of calcium and bypassing the intestinal defect in VDR signaling. In addition to the need for frequent hospitalization and high costs, intravenous administration of calcium is associated with complications and problems such as arrhythmia and sepsis, venous catheter infection and hypercalciuria. This study aims to report the positive treatment effects of high doses of oral calcium in 4 patients with vitamin D-dependent rickets type II. CASE REPORT: In this study, 4 patients with vitamin D-dependent rickets type II, diagnosed based on clinical and biochemical symptoms of rickets with alopecia, underwent therapy using high doses of oral calcium (300 mg/kg/day in pediatric endocrinology and metabolism center of Imam Reza hospital. After a short period, increased growth rate in height, strength and elasticity of muscles was observed in addition to biochemical improvements without serious side effects and even one patient started walking independently within the first week of therapy for the first time. Patients were regularly followed up in terms of height and weight, growth rate and biochemical factors including calcium, phosphorus and alkaline phosphatase every 3 months for one year. CONCLUSION: Regardless of the type of mutation in vitamin D receptor, it is suggested that a 3-6 months trial of high dose oral calcium be started in each patient with vitamin D-dependent rickets type II, particularly for patients whose disease was diagnosed at lower ages.

  18. Treatment of carcinoma of uterine cervix with high-dose-rate intracavitary irradiation using Ralstron

    International Nuclear Information System (INIS)

    Suh, C.O.; Kim, G.E.; Loh, J.J.K.

    1988-01-01

    From May 1979 through December 1981, a total of 530 patients with carcinoma of the uterine cervix were treated with radiation therapy with curative intent. Of the 530 patients, 365 were treated with a high-dose-rate remote-controlled afterloading system (RALS) using a cobalt source, and 165 patients received a low dose rate using a radium source. External pelvic irradiation with a total of 40-50 Gy to the whole pelvis followed by intracavitary radiation (ICR) with a total dose of 30-39 Gy in ten to 13 fractions to point A was the treatment protocol. ICR was given three times a week with a dose of 3 Gy per fraction. Five-year actuarial survival rate with high-dose-rate ICR by stage was as follows: stage I:82.7% (N = 19) stage II:69.6% (N = 184), and stage III:52.2% (N = 156). The above results were comparable with those with conventional low-dose-rate ICR treatment, and late complications were far less. The application of high-dose-rate ICR was technically simple and easily performed on an outpatient basis without anesthesia, and the patients tolerated it very well. Radiation exposure to personnel was virtually none as compared with that of low-dose-rate ICR. Within a given period of time, more patients can be treated with high-dose-rate ICR because of the short treatment time. The authors therefore conclude that high-dose-rate ICR is suitable for a cancer center where a large number of patients are to be treated

  19. High-dose anti-histamine use and risk factors in children with urticaria.

    Science.gov (United States)

    Uysal, Pınar; Avcil, Sibelnur; Erge, Duygu

    2016-12-01

    The drugs of choice in the treatment of urticaria in children are H1-antihistamines. The aim of the study was to evaluate children with urticaria and define risk factors for requirement of high-dose H1-antihistamines in children with urticaria. The medical data of children who were diagnosed as having urticaria admitted to our outpatient clinic between January 2014 and January 2016 were searched. The medical histories, concomitant atopic diseases, parental atopy histories, medications, treatment responses, blood eosinophil and basophil counts, and serum total IgE levels were recorded. In addition, the urticaria activity score for seven days, autoimmune antibody tests, and skin prick test results were evaluated in children with chronic urticaria. The numbers of the children with acute and chronic urticaria were 138 and 92, respectively. The age of the children with chronic urticaria was higher than that of those with acute urticaria (p0.05). There was a negative correlation between blood eosinophil count and the UAS7 score in children with chronic urticaria (r=-0.276, p=0.011). Chronic urticaria and requirement of high dose H1-antihistamines were significant in children aged ≥10 years (p<0.001, p=0.015). High UAS7 score (OR: 1.09; CI 95%: [1.03-1.15]) and basopenia (OR: 6.77; CI 95%: [2.01-22.75]) were associated with the requirement of high-dose H1-AH in children with chronic urticaria. The requirement of high-dose H1-antihistamines was higher with children's increasing age. Disease severity and basopenia were risk factors for the requirement of high-dose H1-antihistamines.

  20. Braquiterapia de alta taxa de dose no Brasil High-dose rate brachytherapy in Brazil

    Directory of Open Access Journals (Sweden)

    Sérgio Carlos Barros Esteves

    2004-10-01

    Full Text Available A braquiterapia de alta taxa de dose foi introduzida em nosso meio em janeiro de 1991. Desde então, houve uma mudança significativa na abordagem das neoplasias malignas em relação às vantagens do novo método, e também resolução da demanda reprimida de braquiterapia para as neoplasias ginecológicas. Nos primeiros dez anos de atividade, o Brasil tratou, em 31 serviços, 26.436 pacientes com braquiterapia, sendo mais de 50% das pacientes portadoras de neoplasias do colo uterino. Este estudo mostra o número e o perfil de pacientes tratados com esse método e a sua distribuição no território nacional, deixando explícito o benefício da braquiterapia de alta taxa de dose para o Brasil.High-dose rate brachytherapy was first introduced in Brazil in January 1991. Significant changes in the management of malignant neoplasms were observed since utilization of high-dose rate brachytherapy. The high number of gynecological patients awaiting for brachytherapy also decreased during this period. In the first ten years 26,436 patients were treated with high-dose rate brachytherapy. More than 50% of these patients presented neoplasms of the uterine cervix. In this study we present the number and profile of the patients treated with high-dose rate brachytherapy as well as the distribution of these patients in the Brazilian territory, proving the benefit of the use of high-dose rate brachytherapy in Brazil.

  1. Impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat

    Directory of Open Access Journals (Sweden)

    Jan Muhammad Shah

    2016-10-01

    Full Text Available Aim: The aim of this study was to evaluate the impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat species. Materials and Methods: Six mature, healthy goats (combine breed and sex with average weight 25 kg were selected for this study. The therapeutic (20 mg/kg b.w. and high doses (40 and 60 mg of florfenicol were administered for 3 days with 24 h interval. Blood samples were collected at 0, 24, 48, 72, 96, and 120 h following the each administered dose. Results: The results showed that the therapeutic dose of florfenicol produced nonsignificant effect on serum urea, creatinine, total protein (TP, alkaline phosphatase (ALP, gamma-glutamyl transferase (GGT and bilirubin on all timings, and increased (p<0.05 the serum glutamic oxaloacetic transaminase (SGOT and serum glutamate-pyruvate transaminase (SGPT levels for 48 h. Whereas the high doses of florfenicol (40 and 60 mg significantly altered the kidney and liver functional indicators in the blood. In contrast with control, the serum urea level was (p<0.01 increased at all timing points. Creatinine values were altered (p<0.01, <0.05 in increasing manner from 24 to 96 h. The high dose of 40 mg decreased the TP (p<0.05 for 72 h and 60 mg persisted same effect (p<0.01 up to 120 h. The indices of ALP, GGT, SGOT, and SGPT were raised (p<0.01, <0.05 at all timings. The bilirubin indexes also (p<0.05 elevated from 48 to 72. Conclusion: It was concluded that the high doses of florfenicol produced reversible dose-dependent effects on functional indicators of kidney and liver such as urea, creatinine, TP, ALP, SGOT, SGPT, GGT, and bilirubin.

  2. Toxicity and cosmetic result of partial breast high-dose-rate interstitial brachytherapy for conservatively operated early breast cancer

    International Nuclear Information System (INIS)

    Xiu Xia; Tripuraneni Prabhakar; Giap Huan; Lin Ray; Chu Colin

    2007-01-01

    Objective: Objective To study the method, side effects and cosmetic outcome of high- dose-rate (HDR) accelerated partial breast interstitial irradiation (APBI) alone in early stage breast cancer' after conservative surgery. Methods: From February 2002 to June 2003,47 breast cancer lesions from 46 patients suffering from stage I/II breast cancer were treated with HDR 192 Ir APBI after conservative surgery. All patients were over 40 year-old, with T1-2N0-1 (≤3 lymph nodes positive), surgical margin > 1-2 mm, but those having lobular or inflammatory breast cancer were excluded. HDR brachytherapy with 34 Gy, 10 fractions/5 days was used after surgery, toxic reaction and cosmetic outcome were observed in one month, 6 and 12 months respectively. Results: Follow up of 1846 months, 34 months was carried out for the whole group. During the treatment, acute reactions including: erythema, edema, tenderness and infection, all under I-II grade, none of III-IV grade were observed in 21 patients(46%); late toxicity reactions: skin fibrosis, breast tenderness, fat necrosis, and telangiectasia, totally 20 patients (43%) were observed: 2 patients in III grade but one patient received 6 cycle chemotherapy. The result of cosmetic outcome evaluation was excellent or good, at 6 months 95% and 12 months 98%, respectively, but there was no recurfence. Conclusions: Excellent and favorable cosmetic results are noted after APBI by interstitial alone. Acute and late reactions are few. Long term observation is necessary for the rate of' local control. (authors)

  3. Intraoperative high-dose-rate brachytherapy for the treatment of pediatric tumors: the Ohio State University experience

    International Nuclear Information System (INIS)

    Nag, Subir; Tippin, Douglas; Ruymann, Frederick B.

    2001-01-01

    Purpose: To determine whether intraoperative high-dose-rate brachytherapy (IO-HDRBT) can be used to decrease the dose of external beam radiotherapy (EBRT) in the treatment of children with soft-tissue sarcomas and, thereby, reduce morbidity without compromising local control. Methods and Materials: From March 1992 through April 1999, 13 pediatric patients were treated with IO-HDRBT, low-dose EBRT, chemotherapy, and radical surgery at 21 sites that were not amenable to intraoperative electron beam therapy. The IO-HDRBT dose at 5 mm depth was 10 to 12.5 Gy for close margins/microscopic disease at 14 sites and 12.5 to 15 Gy for gross disease at 7 sites. The treatment volumes ranged from 4 to 96 cm 3 (mean 27). The EBRT dose was limited to 27-30 Gy in most cases to minimize growth retardation and preserve normal organ function. Results: After a median follow-up of 47 months (range 12-97), 11 patients were alive and without evidence of disease (overall survival rate 85%, 4-year actuarial survival rate 77%). Of the 2 who died, 1 had Stage III pulmonary blastoma with a sacral recurrence; the other had Stage IV undifferentiated synovial sarcoma with a pulmonary recurrence. One local failure occurred in a patient with gross residual disease after incomplete resection for Stage IV pulmonary blastoma. The local control rate was 95%, and morbidity was observed in 3 patients (23%). One patient developed impaired orbital growth with mild ptosis. Another patient required orthopedic pinning of her femoral subcapital epiphysis and construction of a neobladder secondary to urethral obstruction. The third patient required reimplantation of her autotransplanted kidney secondary to chronic urinary tract infection and ureteral reflux. Conclusions: IO-HDRBT allowed for reduction in EBRT without compromising local control or disease-free survival in children with soft-tissue sarcomas. Tumor beds inaccessible to electron beam methods could be satisfactorily encompassed with IO

  4. Dose accumulation of multiple high dose rate prostate brachytherapy treatments in two commercially available image registration systems.

    Science.gov (United States)

    Poder, Joel; Yuen, Johnson; Howie, Andrew; Bece, Andrej; Bucci, Joseph

    2017-11-01

    The purpose of this study was to assess whether deformable image registration (DIR) is required for dose accumulation of multiple high dose rate prostate brachytherapy (HDRPBT) plans treated with the same catheter pattern on two different CT datasets. DIR was applied to 20 HDRPBT patients' planning CT images who received two treatment fractions on sequential days, on two different CT datasets, with the same implant. Quality of DIR in Velocity and MIM image registration systems was assessed by calculating the Dice Similarity Coefficient (DSC) and mean distance to agreement (MDA) for the prostate, urethra and rectum contours. Accumulated doses from each system were then calculated using the same DIR technique and dose volume histogram (DVH) parameters compared to manual addition with no DIR. The average DSC was found to be 0.83 (Velocity) and 0.84 (MIM), 0.80 (Velocity) and 0.80 (MIM), 0.80 (Velocity) and 0.81 (MIM), for the prostate, rectum and urethra contours, respectively. The average difference in calculated DVH parameters between the two systems using dose accumulation was less than 1%, and there was no statistically significant difference found between deformably accumulated doses in the two systems versus manual DVH addition with no DIR. Contour propagation using DIR in velocity and MIM was shown to be at least equivalent to inter-observer contouring variability on CT. The results also indicate that dose accumulation through manual addition of DVH parameters may be sufficient for HDRPBT treatments treated with the same catheter pattern on two different CT datasets. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  5. Adaptive sequential controller

    Energy Technology Data Exchange (ETDEWEB)

    El-Sharkawi, Mohamed A. (Renton, WA); Xing, Jian (Seattle, WA); Butler, Nicholas G. (Newberg, OR); Rodriguez, Alonso (Pasadena, CA)

    1994-01-01

    An adaptive sequential controller (50/50') for controlling a circuit breaker (52) or other switching device to substantially eliminate transients on a distribution line caused by closing and opening the circuit breaker. The device adaptively compensates for changes in the response time of the circuit breaker due to aging and environmental effects. A potential transformer (70) provides a reference signal corresponding to the zero crossing of the voltage waveform, and a phase shift comparator circuit (96) compares the reference signal to the time at which any transient was produced when the circuit breaker closed, producing a signal indicative of the adaptive adjustment that should be made. Similarly, in controlling the opening of the circuit breaker, a current transformer (88) provides a reference signal that is compared against the time at which any transient is detected when the circuit breaker last opened. An adaptive adjustment circuit (102) produces a compensation time that is appropriately modified to account for changes in the circuit breaker response, including the effect of ambient conditions and aging. When next opened or closed, the circuit breaker is activated at an appropriately compensated time, so that it closes when the voltage crosses zero and opens when the current crosses zero, minimizing any transients on the distribution line. Phase angle can be used to control the opening of the circuit breaker relative to the reference signal provided by the potential transformer.

  6. Adaptive sequential controller

    Science.gov (United States)

    El-Sharkawi, Mohamed A.; Xing, Jian; Butler, Nicholas G.; Rodriguez, Alonso

    1994-01-01

    An adaptive sequential controller (50/50') for controlling a circuit breaker (52) or other switching device to substantially eliminate transients on a distribution line caused by closing and opening the circuit breaker. The device adaptively compensates for changes in the response time of the circuit breaker due to aging and environmental effects. A potential transformer (70) provides a reference signal corresponding to the zero crossing of the voltage waveform, and a phase shift comparator circuit (96) compares the reference signal to the time at which any transient was produced when the circuit breaker closed, producing a signal indicative of the adaptive adjustment that should be made. Similarly, in controlling the opening of the circuit breaker, a current transformer (88) provides a reference signal that is compared against the time at which any transient is detected when the circuit breaker last opened. An adaptive adjustment circuit (102) produces a compensation time that is appropriately modified to account for changes in the circuit breaker response, including the effect of ambient conditions and aging. When next opened or closed, the circuit breaker is activated at an appropriately compensated time, so that it closes when the voltage crosses zero and opens when the current crosses zero, minimizing any transients on the distribution line. Phase angle can be used to control the opening of the circuit breaker relative to the reference signal provided by the potential transformer.

  7. Sequential hemi-body radiotherapy in advanced multiple myeloma

    International Nuclear Information System (INIS)

    Jaffe, J.P.; Bosch, A.; Raich, P.C.

    1979-01-01

    Eleven patients with advanced multiple myeloma refractory to standard chemotherapy were treated with a regimen of sequential hemi-body radiotherapy consisting of 800 rad midplane in a single dose to each half. 9/10 patients experienced significant relief of skeletal pain and there were 5/11 objective tumor responses with one complete remission. Treatment-related morbidity was significant and consisted primarily of nausea and emesis, bone marrow suppression, and pneumonitis. This therapy is helpful in the management of advanced myeloma, and should be studied earlier in the course of the disease

  8. Quantum Inequalities and Sequential Measurements

    International Nuclear Information System (INIS)

    Candelpergher, B.; Grandouz, T.; Rubinx, J.L.

    2011-01-01

    In this article, the peculiar context of sequential measurements is chosen in order to analyze the quantum specificity in the two most famous examples of Heisenberg and Bell inequalities: Results are found at some interesting variance with customary textbook materials, where the context of initial state re-initialization is described. A key-point of the analysis is the possibility of defining Joint Probability Distributions for sequential random variables associated to quantum operators. Within the sequential context, it is shown that Joint Probability Distributions can be defined in situations where not all of the quantum operators (corresponding to random variables) do commute two by two. (authors)

  9. Late effects of adjuvant chemotherapy on cognitive function: a follow-up study in breast cancer patients

    NARCIS (Netherlands)

    Schagen, S. B.; Muller, M. J.; Boogerd, W.; Rosenbrand, R. M.; van Rhijn, D.; Rodenhuis, S.; van Dam, F. S. A. M.

    2002-01-01

    BACKGROUND: Neuropsychological examinations have shown an elevated risk for cognitive impairment 2 years after therapy in breast cancer patients randomized to receive adjuvant high-dose cyclophosphamide, thiotepa, carboplatin (CTC) chemotherapy compared with a non-treated control group of stage I

  10. VIM-D salvage chemotherapy in Hodgkin's disease.

    Science.gov (United States)

    Phillips, J K; Spearing, R L; Davies, J M; Hay, C R; Parry, H; Nash, J R; Cawley, J C

    1990-01-01

    A total of 15 patients with relapsed or resistant Hodgkin's disease were treated with a combination of etoposide (VP16), ifosfamide, mitozantrone and dexamethasone (VIM-D). The regime was well tolerated, the only major toxicity being myelosuppression. Complete remissions (CRs) were obtained in 4 patients and were maintained for 2, 4, 10 and 14 months. 10 subjects subsequently received an autologous bone marrow transplant with high-dose chemotherapy (ABMT). Previous exposure to VIM-D did not appear to predict for or prejudice the response to subsequent ABMT.

  11. Dramatic response to high-dose icotinib in a lung adenocarcinoma patient after erlotinib failure.

    Science.gov (United States)

    Guan, Yin; Zhao, Hong; Meng, Jing; Yan, Xiang; Jiao, ShunChang

    2014-02-01

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) retreatment is rarely administered for non-small cell lung cancer (NSCLC) patients who did not respond to previous TKI treatment. A high dose of TKI may overcome resistance to the standard dose of TKI and have different effectiveness toward cancer compared with the standard dose of TKI. This manuscript describes a dramatic and durable response to high-dose icotinib in a NSCLC patient who did not respond to a previous standard dose of erlotinib. The treatment extended the life of the patient for one additional year. A higher dose of icotinib deserves further study not only for patients whose therapy failed with the standard dose of TKI but also for newly diagnosed NSCLC patients with a sensitive mutation. Serial mutation testing during disease development is necessary for analysis and evaluation of EGFR TKI treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Heavy ion time-of-flight ERDA of high dose metal implanted germanium

    Energy Technology Data Exchange (ETDEWEB)

    Dytlewski, N.; Evans, P.J.; Noorman, J.T. [Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW (Australia); Wielunski, L.S. [Commonwealth Scientific and Industrial Research Organisation (CSIRO), Lindfield, NSW (Australia). Div. of Applied Physics; Bunder, J. [New South Wales Univ., Wollongong, NSW (Australia). Wollongong Univ. Coll

    1996-12-31

    With the thick Ge substrates used in ion implantation, RBS can have difficulty in resolving the mass-depth ambiguities when analysing materials composed of mixtures of elements with nearly equal masses. Additional, and complimentary techniques are thus required. This paper reports the use of heavy ion time-of-flight elastic recoil detection analysis (ToF- ERDA), and conventional RBS in the analysis of Ge(100) implanted with high dose Ti and Cu ions from a MEWA ion source . Heavy ion ToF ERDA has been used to resolve, and profile the implanted transition metal species, and also to study any oxygen incorporation into the sample resulting from the implantation, or subsequential reactions with air or moisture. This work is part of a study on high dose metal ion implantation of medium atomic weight semiconductor materials. 13 refs., 6 figs.

  13. Heavy ion time-of-flight ERDA of high dose metal implanted germanium

    Energy Technology Data Exchange (ETDEWEB)

    Dytlewski, N; Evans, P J; Noorman, J T [Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW (Australia); Wielunski, L S [Commonwealth Scientific and Industrial Research Organisation (CSIRO), Lindfield, NSW (Australia). Div. of Applied Physics; Bunder, J [New South Wales Univ., Wollongong, NSW (Australia). Wollongong Univ. Coll

    1997-12-31

    With the thick Ge substrates used in ion implantation, RBS can have difficulty in resolving the mass-depth ambiguities when analysing materials composed of mixtures of elements with nearly equal masses. Additional, and complimentary techniques are thus required. This paper reports the use of heavy ion time-of-flight elastic recoil detection analysis (ToF- ERDA), and conventional RBS in the analysis of Ge(100) implanted with high dose Ti and Cu ions from a MEWA ion source . Heavy ion ToF ERDA has been used to resolve, and profile the implanted transition metal species, and also to study any oxygen incorporation into the sample resulting from the implantation, or subsequential reactions with air or moisture. This work is part of a study on high dose metal ion implantation of medium atomic weight semiconductor materials. 13 refs., 6 figs.

  14. High dose rate intracavitary afterloading irradiation in malignant inoperable obturation of bile ducts

    Energy Technology Data Exchange (ETDEWEB)

    Itami, J.; Saegusa, K.; Mamiya, T.; Miyoshi, T.; Arimizu, N.; Tsuchiya, Y.; Ohto, M.

    1986-02-01

    After decompression of the bile duct with PTCD, seven patients with carcinomas of the bile ducts were submitted to an intracavitary Ir-afterloading irradiation performed according to the high-dose-rate method with a Buchler device. Most of the patients were irradiated with 30 Gy in two fractions. Five patients were also exposed to percutaneous radiation with 40 to 50 Gy. Local control was achieved in six patients. One patient developed a locoregional recurrence which was possibly due to a so-called 'geographic miss'. In one patient a benign fibrotic stenosis of the bile duct was found at the site of most intensive irradiation. Intracavitary irradiation is very important in the treatment of malignant of bile ducts. However, there is an urgent need of research with regard to the combined method with percutaneous irradiation and to the optimum fractionation of intracavitary high dose rate irradiation.

  15. Evaluation of glasses containing cadmium for high dose dosimetry by the thermoluminescence technique

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, Gabriel Soares Marchiori de; Ferreira, Pamela Zati; Cunha, Diego Merigue da; Dantas, Noelio Oliveira; Silva, Anielle C.A.; Perini, Ana Paula; Neves, Lucio Pereira, E-mail: lucio.neves@ufu.br [Universidade Federal de Uberlandia (INFIS/UFU), MG (Brazil). Instituto de Fisica; Caldas, Linda V.E. [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil); Carrera, Betzabel Noemi Silva; Watanabe, Shigueo [Universidade de Sao Paulo (IF/USP), SP (Brazil). Instituto de Fisica

    2016-07-01

    New glass matrices were evaluated for high dose dosimetry by the thermoluminescence technique. Their nominal composition are 20Li{sub 2}CO{sub 3}.10Al{sub 2}O{sub 3}.15CdO.55B{sub 2}O{sub 3} and 20Li{sub 2}CO{sub 3}.10Al{sub 2}O{sub 3}.20CdO.50B{sub 2}O{sub 3} (mol%). The glass matrices were irradiated with different doses: 50, 100, 200, 500, 700 and 900 Gy, and the thermoluminescence emission curves were obtained for each of these values. The results show a great potential of using these matrices in high dose dosimetry. (author)

  16. Study of a new glass matrix by thermoluminescent technique for high-dose dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Pamela Z.; Carvalho, Gabriel S. Marchiori de; Cunha, Diego M. da; Dantas, Noelio O.; Silva, Anielle C.A.; Neves, Lucio P.; Perini, Ana P., E-mail: anapaula.perini@ufu.br [Universidade Federal de Uberlandia (UFU), MG (Brazil). Instituto de Fisica; Linda, V.E. Caldas [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Carrera, Betzabel N.S.; Watanabe, Shigueo [Universidade de Sao Paulo (IF/USP), Sao Paulo, SP (Brazil). Instituto de Fisica

    2016-07-01

    The thermoluminescence technique is widely used for both personal and for high-dose dosimetry. In this work, the thermoluminescence technique was utilized to study a new glass matrix, with nominal composition of 20Li{sub 2}CO{sub 3}.10Al{sub 2}O{sub 3}.30BaO.40B{sub 2}O{sub 3} (mol%), irradiated with different doses in a {sup 60}Co source. The glow curves and the dose-response curve were obtained for radiation doses of 10, 50, 100, 200 e 700 Gy. The results showed that this new glass matrix has potential use in high-dose dosimetry. (author)

  17. Practice for characterization and performance of a high-dose radiation dosimetry calibration laboratory

    International Nuclear Information System (INIS)

    2003-01-01

    This practice addresses the specific requirements for laboratories engaged in dosimetry calibrations involving ionizing radiation, namely, gamma-radiation, electron beams or X-radiation (bremsstrahlung) beams. It specifically describes the requirements for the characterization and performance criteria to be met by a high-dose radiation dosimetry calibration laboratory. The absorbed-dose range is typically between 10 and 10 5 Gy. This practice addresses criteria for laboratories seeking accreditation for performing high-dose dosimetry calibrations, and is a supplement to the general requirements described in ISO/IEC 17025. By meeting these criteria and those in ISO/IEC 17025, the laboratory may be accredited by a recognized accreditation organization. Adherence to these criteria will help to ensure high standards of performance and instill confidence regarding the competency of the accredited laboratory with respect to the services it offers

  18. Synergies Between ' and Cavity Formation in HT-9 Following High Dose Neutron Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Field, Kevin G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Parish, Chad M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Saleh, Tarik A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Eftink, Benjamin P. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-06-01

    Candidate cladding materials for advanced nuclear power reactors including fast reactor designs require materials capable of withstanding high dose neutron irradiation at elevated temperatures. One candidate material, HT-9, through various research programs have demonstrated the ability to withstand significant swelling and other radiation-induced degradation mechanisms in the high dose regime (>50 displacements per atom, dpa) at elevated temperatures (>300 C). Here, high efficiency multi-dimensional scanning transmission electron microscopy (STEM) acquisition with the aid of a three-dimensional (3D) reconstruction and modeling technique is used to probe the microstructural features that contribute to the exceptional swelling resistance of HT-9. In particular, the synergies between ' and fine-scale and moderate-scale cavity formation is investigated.

  19. CT of multiple sclerosis: reassessment of delayed scanning with high doses of contrast material

    International Nuclear Information System (INIS)

    Spiegel, S.M.; Vinuela, F.; Fox, A.J.; Pelz, D.M.

    1985-01-01

    A prospective study involving 87 patients was carried out to evaluate the necessity for a high dose of contrast material in addition to delayed computed tomographic (CT) scanning for optimal detection of the lesions of multiple sclerosis in the brain. In patients with either clinically definite multiple sclerosis or laboratory-supported definite multiple sclerosis, CT scans were obtained with a uniform protocol. Lesions consistent with multiple sclerosis were demonstrated on the second scan in 54 patients. In 36 of these 54 patients, the high-dose delayed scan added information. These results are quite similar to those of a previous study from this institution using different patients, in whom the second scan was obtained immediately after the bolus injection of contrast material containing 40 g of organically bound iodine. The lack of real difference in the results of the two studies indicate that the increased dose, not just the delay in scanning, is necessary for a proper study

  20. Gene expression profiles following high-dose exposure to gamma radiation in salmonella enterica serovar typhimurium

    International Nuclear Information System (INIS)

    Lim, Sang Yong; Jung, Sun Wook; Joe, Min Ho; Kim, Dong Ho

    2008-01-01

    Microarrays can measure the expression of thousands of genes to identify the changes in expression between different biological states. To survey the change of whole Salmonella genes after a relatively high dose of gamma radiation (1 kGy), transcriptome dynamics were examined in the cells by using DNA microarrays. At least 75 genes were induced and 89 genes were reduced two-fold or more after irradiation. Several genes located in pSLT plasmid, cyo operon, and Gifsy prophage were induced along with many genes encoding uncharacterized proteins.While, the expression of genes involved in the virulence of Salmonella as well as metabolic functions were decreased. Although the radiation response as a whole could not be illustrated by using DNA microarrays, the data suggest that the response to high dose of irradiation might be more complex than the SOS response

  1. No seasonal accumulation of resistant P. falciparum when high-dose chloroquine is used

    DEFF Research Database (Denmark)

    Ursing, Johan; Kofoed, Poul-Erik; Rodrigues, Amabelia

    2009-01-01

    increase of pfcrt 76T if the high doses of CQ commonly used are effective. METHODS AND FINDINGS: P. falciparum parasite density, age, sex, the proportion of chloroquine resistance associated haplotypes pfcrt 76T and P. falciparum multidrug resistance gene 1 86Y were assessed in 988 samples collected from...... to become the dominant P.falciparum type in Guinea-Bissau. This is most likely due to the efficacy of high-dose chloroquine as used in Guinea-Bissau, combined with a loss of fitness associated with pfcrt 76T.......BACKGROUND: Potentially chloroquine resistant P. falciparum, identified by the 76T haplotype in the chloroquine resistance transporter (pfcrt 76T), are highly prevalent throughout Africa. In Guinea-Bissau, normal and double dose chloroquine have respective efficacies of 34% and 78% against P...

  2. The radiosensitizing effect of doranidazole on human colorectal cancer cells exposed to high doses of irradiation

    International Nuclear Information System (INIS)

    Zhang, Li; Gong, Aimin; Ji, Jun; Wu, Yuanyuan; Zhu, Xiaoyu; Lv, Suqing; Lv, Hongzhu; Sun, Xizhuo

    2007-01-01

    This paper investigates the effects of a new radiosensitizer, doranidazole, and enhancing irradiation on colorectal cancer cells. The radiosensitizing effect of doranidazole was determined using colony formation and propidium iodide (PI) assays to measure cell growth inhibition and the cell killing effect of human colorectal cancer cell lines exposed to high doses of γ-ray irradiation under hypoxic conditions in vitro. Fluorescence staining and cell migration assays were also used to assess the radiosensitizing effect. Cell proliferation evaluated by clonogenic survival curves was significantly inhibited by 5 mmol/L doranidazole, particularly at doses ranging from 10 to 30 Gy of irradiation. The radiosensitizing effect of doranidazole on colorectal cancer cells occurs in a time- and dose-dependent manner. Doranidazole also inhibited the mobility of cell invasion and migration. Doranidazole can enhance the killing effect and the cell growth inhibition of colorectal cancer after high-dose irradiation in a time and dose-dependent manner

  3. Gene expression profiles following high-dose exposure to gamma radiation in salmonella enterica serovar typhimurium

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sang Yong; Jung, Sun Wook; Joe, Min Ho; Kim, Dong Ho [Radiation Research Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2008-08-15

    Microarrays can measure the expression of thousands of genes to identify the changes in expression between different biological states. To survey the change of whole Salmonella genes after a relatively high dose of gamma radiation (1 kGy), transcriptome dynamics were examined in the cells by using DNA microarrays. At least 75 genes were induced and 89 genes were reduced two-fold or more after irradiation. Several genes located in pSLT plasmid, cyo operon, and Gifsy prophage were induced along with many genes encoding uncharacterized proteins.While, the expression of genes involved in the virulence of Salmonella as well as metabolic functions were decreased. Although the radiation response as a whole could not be illustrated by using DNA microarrays, the data suggest that the response to high dose of irradiation might be more complex than the SOS response.

  4. High-dose therapy improved the bone remodelling compartment canopy and bone formation in multiple myeloma

    DEFF Research Database (Denmark)

    Hinge, Maja; Delaissé, Jean-Marie; Plesner, Torben

    2015-01-01

    transplantation, and from 20 control patients with monoclonal gammopathy of undetermined significance were histomorphometrically investigated. This investigation confirmed that MM patients exhibited uncoupled bone formation to resorption and reduced canopy coverage. More importantly, this study revealed......Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling....... Loss of this canopy has been associated with bone loss. This study addresses whether the bone remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained from 20 MM patients, before and after first-line treatment with high-dose melphalan followed by autologous stem cell...

  5. Framework for sequential approximate optimization

    NARCIS (Netherlands)

    Jacobs, J.H.; Etman, L.F.P.; Keulen, van F.; Rooda, J.E.

    2004-01-01

    An object-oriented framework for Sequential Approximate Optimization (SAO) isproposed. The framework aims to provide an open environment for thespecification and implementation of SAO strategies. The framework is based onthe Python programming language and contains a toolbox of Python

  6. A photocurrent compensation method of bipolar transistors under high dose rate radiation and its experimental research

    International Nuclear Information System (INIS)

    Yin Xuesong; Liu Zhongli; Li Chunji; Yu Fang

    2005-01-01

    Experiment using discrete bipolar transistors has been performed to verify the effect of the photocurrent compensation method. The theory of the dose rate effects of bipolar transistors and the photocurrent compensation method are introduced. The comparison between the response of hardened and unhardened circuits under high dose rate radiation is discussed. The experimental results show instructiveness to the hardness of bipolar integrated circuits under transient radiation. (authors)

  7. High dose radiation damage in nuclear energy structural materials investigated by heavy ion irradiation simulation

    International Nuclear Information System (INIS)

    Zheng Yongnan; Xu Yongjun; Yuan Daqing

    2014-01-01

    Structural materials in ITER, ADS and fast reactor suffer high dose irradiations of neutrons and/or protons, that leads to severe displacement damage up to lOO dpa per year. Investigation of radiation damage induced by such a high dose irradiation has attracted great attention along with the development of nuclear energy facilities of new generation. However, it is deeply hampered for the lacking of high dose neutron and proton sources. Irradiation simulation of heavy ions produced by accelerators opens up an effective way for laboratory investigation of high dose irradiation induced radiation damage encountered in the ITER, ADS, etc. Radiation damage is caused mainly by atomic displacement in materials. The displacement rate of heavy ions is about lO 3 ∼10 7 orders higher than those of neutrons and protons. High displacement rate of heavy ions significantly reduces the irradiation time. The heavy ion irradiation simulation technique (HIIS) technique has been developed at China Institute of Atomic Energy and a series of the HIIS experiments have been performed to investigate radiation damage in stainless steels, tungsten and tantalum at irradiation temperatures from room temperature to 800 ℃ and in the irradiation dose region up to 100 dpa. The experimental results show that he radiation swelling peak for the modified stainless steel appears in the temperature region around 580 ℃ and the radiation damage is more sensitive to the temperature, the size of the radiation induced vacancy cluster or void increase with the increasing of the irradiation dose, and among the three materials the home-made modified stainless steel has the best radiation resistant property. (authors)

  8. Persistent DNA damage after high dose in vivo gamma exposure of minipig skin.

    Directory of Open Access Journals (Sweden)

    Emad A Ahmed

    Full Text Available Exposure to high doses of ionizing radiation (IR can lead to localized radiation injury of the skin and exposed cells suffer dsDNA breaks that may elicit cell death or stochastic changes. Little is known about the DNA damage response after high-dose exposure of the skin. Here, we investigate the cellular and DNA damage response in acutely irradiated minipig skin.IR-induced DNA damage, repair and cellular survival were studied in 15 cm(2 of minipig skin exposed in vivo to ~50 Co-60 γ rays. Skin biopsies of control and 4 h up to 96 days post exposure were investigated for radiation-induced foci (RIF formation using γ-H2AX, 53BP1, and active ATM-p immunofluorescence. High-dose IR induced massive γ-H2AX phosphorylation and high 53BP1 RIF numbers 4 h, 20 h after IR. As time progressed RIF numbers dropped to a low of 3-fold elevated at all subsequent time points. Replicating basal cells (Ki67+ were reduced 3 days post IR followed by increased proliferation and recovery of epidermal cellularity after 28 days.Acute high dose irradiation of minipig epidermis impaired stem cell replication and induced elevated apoptosis from 3 days onward. DNA repair cleared the high numbers of DBSs in skin cells, while RIFs that persisted in <1% cells marked complex and potentially lethal DNA damage up to several weeks after exposure. An elevated frequency of keratinocytes with persistent RIFs may thus serve as indicator of previous acute radiation exposure, which may be useful in the follow up of nuclear or radiological accident scenarios.

  9. High-Dose Mannose-Binding Lectin Therapy for Ebola Virus Infection

    Science.gov (United States)

    2010-06-01

    host defense against a wide range of viral and other pathogens. MBL is a C-type lectin that recognizes hexose sugars including man- nose, glucose...should be evaluatedmore broadly as an immunotherapeutic agent for a wide spectrum of glycosylated pathogens. MATERIALS AND METHODS Production and... coagulation mod- ulators, antisense technologies, therapeutic antibodies and Table 1. Pharmacokinetic Parameters of Low- vs High-Dose Recombinant Human

  10. Biological dose estimation for accidental supra-high dose gamma-ray exposure

    International Nuclear Information System (INIS)

    Chen, Y.; Yan, X.K.; Du, J.; Wang, Z.D.; Zhang, X.Q.; Zeng, F.G.; Zhou, P.K.

    2011-01-01

    To correctly estimate the biological dose of victims accidentally exposed to a very high dose of 60 Co gamma-ray, a new dose-effect curve of chromosomal dicentrics/multicentrics and rings in the supra-high dose range was established. Peripheral blood from two healthy men was irradiated in vitro with doses of 60 Co gamma-rays ranging from 6 to 22 Gy at a dose rate of 2.0 Gy/min. Lymphocytes were concentrated, cultured and harvested at 52 h, 68 h and 72 h. The numbers of dic + r were counted. The dose-effect curves were established and validated using comparisons with doses from the Tokai-mura accident and were then applied to two victims of supra-high dose exposure accident. The results indicated that there were no significant differences in chromosome aberration frequency among the different culture times from 52 h to 72 h. The 6-22 Gy dose-effect curve was fitted to a linear quadratic model Y = -2.269 + 0.776D - 7.868 x l0 -3 D 2 . Using this mathematic model, the dose estimates were similar to data from Tokai-mura which were estimated by PCC ring. Whole body average doses of 9.7 Gy and 18.1 Gy for two victims in the Jining accident were satisfactorily given. We established and successfully applied a new dose-effect curve of chromosomal dicentrics plus ring (dic + r) after 6-22 Gy γ-irradiation from a supra-high dose 60 Co gamma-ray accident.

  11. Quality control of 192Ir high dose rate after loading brachytherapy dose veracity

    International Nuclear Information System (INIS)

    Feng Zhongsu; Xu Xiao; Liu Fen

    2008-01-01

    Recently, 192 Ir high dose rate (HDR) afterloading are widely used in brachytherapy. The advantage of using HDR systems over low dose rate systems are shorter treatment time and higher fraction dose. To guarantee the veracity of the delivery dose, several quality control methods are deseribed in this work. With these we can improve the position precision, time precision and dose precision of the brachytherapy. (authors)

  12. Rapid Onset of Retinal Toxicity From High-Dose Hydroxychloroquine Given for Cancer Therapy.

    Science.gov (United States)

    Leung, Loh-Shan B; Neal, Joel W; Wakelee, Heather A; Sequist, Lecia V; Marmor, Michael F

    2015-10-01

    To report rapid onset of retinal toxicity in a series of patients followed on high-dose (1000 mg daily) hydroxychloroquine during an oncologic clinical trial studying hydroxychloroquine with erlotinib for non-small cell lung cancer. Retrospective observational case series. Ophthalmic surveillance was performed on patients in a multicenter clinical trial testing high-dose (1000 mg daily) hydroxychloroquine for advanced non-small cell lung cancer. The US Food & Drug Administration-recommended screening protocol included only visual acuity testing, dilated fundus examination, Amsler grid testing, and color vision testing. In patients seen at Stanford, additional sensitive screening procedures were added at the discretion of the retinal physician: high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, Humphrey visual field (HVF) testing, and multifocal electroretinography (mfERG). Out of the 7 patients having exposure of at least 6 months, 2 developed retinal toxicity (at 11 and 17 months of exposure). Damage was identified by OCT imaging, mfERG testing, and, in 1 case, visual field testing. Fundus autofluorescence imaging remained normal. Neither patient had symptomatic visual acuity loss. These cases show that high doses of hydroxychloroquine can initiate the development of retinal toxicity within 1-2 years. Although synergy with erlotinib is theoretically possible, there are no prior reports of erlotinib-associated retinal toxicity despite over a decade of use in oncology. These results also suggest that sensitive retinal screening tests should be added to ongoing and future clinical trials involving high-dose hydroxychloroquine to improve safety monitoring and preservation of vision. Published by Elsevier Inc.

  13. Controversies in external beam and high dose rate brachytherapy of oesophageal cancer

    International Nuclear Information System (INIS)

    Sur, R.K.; Levin, V.C.; Malas, Simon; Donde, Bernard

    1994-01-01

    Various controversies in the treatment of oesophageal carcinoma with external beam radiotherapy and high dose rate intracavitary irradiation have been reviewed. Conflicting results from different parts of the world has made it difficult to optimize the radiation dose that may give the best results. More studies and longer follow-up are needed before a definite conclusion can be made on the optimization of dose. (author). 18 refs., 2 tabs

  14. Non-linear failure analysis of HCPB blanket for DEMO taking into account high dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Aktaa, J., E-mail: jarir.aktaa@kit.edu [Karlsruhe Institute of Technology (KIT), Institute for Applied Materials, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany); Kecskés, S.; Pereslavtsev, P.; Fischer, U.; Boccaccini, L.V. [Karlsruhe Institute of Technology (KIT), Institute for Neutron Physics and Reactor Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany)

    2014-10-15

    Highlights: • First non-linear structural analysis for the European Helium Cooled Pebble Bed Blanket Module taking into account high dose irradiation. • Most critical areas were identified and analyzed with regard to the effect of irradiation on predicted damage at these areas. • Despite the extensive computing time 100 cycles were simulated by using the sub-modelling technique investigating damage at most critical area. • The results show a positive effect of irradiation on calculated damage which is mainly attributed to the irradiation induced hardening. - Abstract: For the European helium cooled pebble bed (HCPB) blanket of DEMO the reduced activation ferritic martensitic steel EUROFER has been selected as structural material. During operation the HCPB blanket will be subjected to complex thermo-mechanical loadings and high irradiation doses. Taking into account the material and structural behaviour under these conditions is a precondition for a reliable blanket design. For considering high dose irradiation in structural analysis of the DEMO blanket, the coupled deformation damage model, extended recently taking into account the influence of high dose irradiation on the material behaviour of EUROFER and implemented in the finite element code ABAQUS, has been used. Non-linear finite element (FE) simulations of the DEMO HCPB blanket have been performed considering the design of the HCPB Test Blanket Module (TBM) as reference and the thermal and mechanical boundary conditions of previous analyses. The irradiation dose rate required at each position in the structure as an additional loading parameter is estimated by extrapolating the results available for the TBM in ITER scaling the value calculated in neutronics and activation analysis for ITER boundary conditions to the DEMO boundary conditions. The results of the FE simulations are evaluated considering damage at most critical highly loaded areas of the structure and discussed with regard to the impact of

  15. Charge collection efficiency in ionization chambers exposed to electron beams with high dose per pulse

    Energy Technology Data Exchange (ETDEWEB)

    Laitano, R F [Istituto Nazionale di Metrologia delle Radiazioni Ionizzanti, ENEA Centro Ricerche Casaccia, c.p. 2400 Rome (Italy); Guerra, A S [Istituto Nazionale di Metrologia delle Radiazioni Ionizzanti, ENEA Centro Ricerche Casaccia, c.p. 2400 Rome (Italy); Pimpinella, M [Istituto Nazionale di Metrologia delle Radiazioni Ionizzanti, ENEA Centro Ricerche Casaccia, c.p. 2400 Rome (Italy); Caporali, C [Istituto Nazionale di Metrologia delle Radiazioni Ionizzanti, ENEA Centro Ricerche Casaccia, c.p. 2400 Rome (Italy); Petrucci, A [A.C.O. S. Filippo Neri, U.O. Fisica Sanitaria, Rome (Italy)

    2006-12-21

    The correction for charge recombination was determined for different plane-parallel ionization chambers exposed to clinical electron beams with low and high dose per pulse, respectively. The electron energy was nearly the same (about 7 and 9 MeV) for any of the beams used. Boag's two-voltage analysis (TVA) was used to determine the correction for ion losses, k{sub s}, relevant to each chamber considered. The presence of free electrons in the air of the chamber cavity was accounted for in determining k{sub s} by TVA. The determination of k{sub s} was made on the basis of the models for ion recombination proposed in past years by Boag, Hochhaeuser and Balk to account for the presence of free electrons. The absorbed dose measurements in both low-dose-per-pulse (less than 0.3 mGy per pulse) and high-dose-per-pulse (20-120 mGy per pulse range) electron beams were compared with ferrous sulphate chemical dosimetry, a method independent of the dose per pulse. The results of the comparison support the conclusion that one of the models is more adequate to correct for ion recombination, even in high-dose-per-pulse conditions, provided that the fraction of free electrons is properly assessed. In this respect the drift velocity and the time constant for attachment of electrons in the air of the chamber cavity are rather critical parameters because of their dependence on chamber dimensions and operational conditions. Finally, a determination of the factor k{sub s} was also made by zero extrapolation of the 1/Q versus 1/V saturation curves, leading to the conclusion that this method does not provide consistent results in high-dose-per-pulse beams.

  16. Radiation proctitis after the high dose rate brachytherapy for prostate cancer

    International Nuclear Information System (INIS)

    Kitano, Masashi; Katsumata, Tomoe; Satoh, Takefumi

    2006-01-01

    We reviewed the medical records of 12 patients treated for rectal bleeding after high-dose rate brachytherapy for prostate cancer. All patients developed grade 2 proctitis according to the Common Terminology Criteria for Adverse Events (CTCAC) and no patients needed blood transfusion. The patients were treated with argon plasma coagulation (APC) and/or steroid suppositories. The bleeding stopped or improved in 11 patients. Although re-bleeding was noticed in 7 patients the same treatment was effective in 5 patients. (author)

  17. Non-linear failure analysis of HCPB blanket for DEMO taking into account high dose irradiation

    International Nuclear Information System (INIS)

    Aktaa, J.; Kecskés, S.; Pereslavtsev, P.; Fischer, U.; Boccaccini, L.V.

    2014-01-01

    Highlights: • First non-linear structural analysis for the European Helium Cooled Pebble Bed Blanket Module taking into account high dose irradiation. • Most critical areas were identified and analyzed with regard to the effect of irradiation on predicted damage at these areas. • Despite the extensive computing time 100 cycles were simulated by using the sub-modelling technique investigating damage at most critical area. • The results show a positive effect of irradiation on calculated damage which is mainly attributed to the irradiation induced hardening. - Abstract: For the European helium cooled pebble bed (HCPB) blanket of DEMO the reduced activation ferritic martensitic steel EUROFER has been selected as structural material. During operation the HCPB blanket will be subjected to complex thermo-mechanical loadings and high irradiation doses. Taking into account the material and structural behaviour under these conditions is a precondition for a reliable blanket design. For considering high dose irradiation in structural analysis of the DEMO blanket, the coupled deformation damage model, extended recently taking into account the influence of high dose irradiation on the material behaviour of EUROFER and implemented in the finite element code ABAQUS, has been used. Non-linear finite element (FE) simulations of the DEMO HCPB blanket have been performed considering the design of the HCPB Test Blanket Module (TBM) as reference and the thermal and mechanical boundary conditions of previous analyses. The irradiation dose rate required at each position in the structure as an additional loading parameter is estimated by extrapolating the results available for the TBM in ITER scaling the value calculated in neutronics and activation analysis for ITER boundary conditions to the DEMO boundary conditions. The results of the FE simulations are evaluated considering damage at most critical highly loaded areas of the structure and discussed with regard to the impact of

  18. Influence of high dose irradiation on core structural and fuel materials in advanced reactors

    International Nuclear Information System (INIS)

    1998-08-01

    The IAEA International Working Group on Fast Reactors (IWGFR) periodically organizes meeting to discuss and review important aspects of fast reactor technology. The fifth meeting held in Obninsk, Russian Federation, 16-19 June 1997, was devoted to the influence of high dose irradiation on the mechanical properties of reactor core structural and fuel materials. The proceedings includes the papers submitted at this meeting each with a separate abstract

  19. Salvage high-dose-rate interstitial brachytherapy for locally recurrent rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pellizzon, Antonio Cassio Assis, E-mail: acapellizzon@hcancer.org.br [A.C. Camargo Cancer Center, Sao Paulo, SP (Brazil). Departamento de Radioterapia

    2016-05-15

    For tumors of the lower third of the rectum, the only safe surgical procedure is abdominal-perineal resection. High-dose-rate interstitial brachytherapy is a promising treatment for local recurrence of previously irradiated lower rectal cancer, due to the extremely high concentrated dose delivered to the tumor and the sparing of normal tissue, when compared with a course of external beam radiation therapy. (author)

  20. Management of hilar bile duct carcinoma with high-dose radiotherapy and expandable metallic stent placement

    International Nuclear Information System (INIS)

    Saito, Hiroya; Takamura, Akio

    2000-01-01

    This article describes our experience with high-dose radiotherapy in combination with the placement of expandable metallic stents (EMS) in the management of hilar bile duct carcinoma. Between 1988 and 1999, 107 consecutive patients with hilar bile duct carcinoma were treated with EMS placement either alone or in combination with high-dose radiotherapy. External beam radiotherapy (EBRT) was indicated in 101 patients, and in 86 this was combined with intraluminal 192 Ir irradiation (ILRT, 59-98 Gy) EMS were placed after the completion of radiotherapy. The 1-, 2-, 3-, and 5-year actuarial survival rates for the radiotherapy group were 66.4%, 23.4%, 15.6%, 7.8%, respectively, and the 1- and 2-year actuarial survival rates for the nonradiotherapy group were 66.4% and 0%, respectively. The placement of EMS was useful for the early establishment of an internal bile passage in radically irradiated patients and the 1-, 2-, 3-, and 5-year actuarial patency rates for the radiotherapy group were 56.3%, 45.3%, 35.2%, and 23.4%, respectively, and the 1- and 2-year actuarial patency rates for the non radiotherapy group were 50.0% and 0% respectively. High-dose radiotherapy, consisting of ILRT and EBRT, appears to be feasible in the management of hilar bile duct carcinoma, and it offers a survival advantage for patients no suited for surgical resection. The placement of EMS assists the internal bile flow and lengthens survival after high-dose radiotherapy. (author)

  1. Treating tuberculosis with high doses of anti-TB drugs: mechanisms and outcomes.

    Science.gov (United States)

    Xu, Yuhui; Wu, Jianan; Liao, Sha; Sun, Zhaogang

    2017-10-03

    Tuberculosis (TB) is considered as one of the most serious threats to public health in many parts of the world. The threat is even more severe in the developing countries where there is a lack of advanced medical amenities and contemporary anti-TB drugs. In such situations, dosage optimization of existing medication regimens seems to be the only viable option. Therapeutic drug monitoring study results suggest that high-dose treatment regimens can compensate the low serum concentration of anti-TB drugs and shorten the therapy duration. The article presents a critical review on the possible changes that occur in the host and the pathogen upon the administration of standard and high-dose regimens. Some of the most common factors that are responsible for low anti-TB drug concentrations in the serum are differences in hosts' body weight, metabolic processing of the drug, malabsorption and/or drug-drug interaction. Furthermore, failure to reach the cavitary pulmonary and extrapulmonary tissues also contributes to the therapeutic inefficiency of the drugs. In such conditions, administration of higher doses can help in compensating the pathogenic outcomes of enhancement of the pathogen's physical barriers, efflux pumps and genetic mutations. The present article also presents a summary of the recorded treatment outcomes of clinical trials that were conducted to test the efficacy of administration of high dose of anti-tuberculosis drugs. This review will help physicians across the globe to understand the underlying pathophysiological changes (including side effects) that dictate the clinical outcomes in patients administered with standard and/or high dose anti-TB drugs.

  2. Epithelial regeneration of transposed intestine after high doses of X irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Both, N.J. de; Vermey, M [Erasmus Universiteit, Rotterdam (Netherlands)

    1976-01-01

    The regeneration capacities of normal and transposed small bowel epithelium were compared in rats after applying high doses of x irradiation. It has been shown that the potency of the mucosa to regenerate was much higher than assumed and that the mucosa could regenerate after single doses varying from 2000 to 5000 R. Even in the villus epithelium and in flat epithelium covering infiltrates of the lamina propria cells survived, which were still able to resume proliferative activity several days after irradiation.

  3. Sequentially pulsed traveling wave accelerator

    Science.gov (United States)

    Caporaso, George J [Livermore, CA; Nelson, Scott D [Patterson, CA; Poole, Brian R [Tracy, CA

    2009-08-18

    A sequentially pulsed traveling wave compact accelerator having two or more pulse forming lines each with a switch for producing a short acceleration pulse along a short length of a beam tube, and a trigger mechanism for sequentially triggering the switches so that a traveling axial electric field is produced along the beam tube in synchronism with an axially traversing pulsed beam of charged particles to serially impart energy to the particle beam.

  4. Polybutadiene and Styrene-Butadiene rubbers for high-dose dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Lucas N. [Instituto Federal de Educacao, Ciencia e Tecnologia de Goias-IFG,Campus Goiania, Goiania -GO (Brazil); Instituto de Pesquisas Energeticas e Nucleares -IPEN, Sao Paulo-SP (Brazil); Vieira, Silvio L. [Instituto de Fisica, Universidade Federal de Goias-UFG, Campus Samambaia, Goiania-GO (Brazil); Schimidt, Fernando [Instituto Federal de Educacao, Ciencia e Tecnologia de Goias-IFG,Campus Inhumas, Inhumas-GO (Brazil); Antonio, Patricia L.; Caldas, Linda V.E. [Instituto de Pesquisas Energeticas e Nucleares -IPEN, Sao Paulo-SP (Brazil)

    2015-07-01

    Polybutadiene and Styrene-Butadiene are synthetical rubbers used widely for pneumatic tires manufacturing. In this research, the dosimeter characteristics of those rubbers were studied for application in high-dose dosimetry. The rubber samples were irradiated with doses of 10 Gy up to 10 kGy, using a {sup 60}Co Gamma Cell-220 system (dose rate of 1.089 kGy/h) and their readings were taken on a Fourier Transform Infrared Spectroscopy-FTIR system (model Frontier/Perkin Elmer). The ratios of two absorbance peaks were taken for each kind of rubber spectrum, Polybutadiene (1306/1130 cm{sup -1}) and Styrene-Butadiene (1449/1306 cm{sup -1}). The ratio calculated was used as the response to the irradiation, and is not uniform across the sample. From the results, it can be concluded for both rubbers: a) the dose-response curves may be useful for high-dose dosimetry (greater than 250 Gy); b) their response for reproducibility presented standard deviations lower than 2.5%; c) the relative sensitivity was higher for Styrene-Butadiene (1.86 kGy{sup -1}) than for Polybutadiene (1.81 kGy{sup -1}), d) for doses of 10 kGy to 200 kGy, there was no variation in the dosimetric response. Both types of rubber samples showed usefulness as high-dose dosimeters. (authors)

  5. Cosmetic results in early stage breast cancer patients with high-dose brachytherapy after conservative surgery

    International Nuclear Information System (INIS)

    Torres, Felipe; Pineda, Beatriz E

    2004-01-01

    Purpose: to reveal cosmetic results in patients at early stages of low risk breast cancer treated with partial accelerated radiotherapy using high dose rate brachytherapy. Methods and materials: from March 2001 to July 2003,14 stages l and ll breast cancer patients were treated at the Colombian national cancer institute in Bogota with conservative surgery and radiotherapy upon the tumor bed (partial accelerated radiotherapy), using interstitial implants with iridium 192 (high dose rate brachytherapy) with a dose of 32 Gys, over 4 days, at 8 fractions twice a day. Results: with an average follow up of 17.7 months, good cosmetic results were found among 71.4 % of patients and excellent results among 14.3% of patients, furthermore none of the patients neither local nor regional or distant relapses. Conclusion: among patients who suffer from breast cancer at early stages, it showed is possible to apply partial accelerated radiotherapy upon the tumor bed with high doses over 4 days with good to excellent cosmetic results

  6. Development of computerized dose planning system and applicator for high dose rate remote afterloading irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, T. J. [Keimyung Univ., Taegu (Korea); Kim, S. W. [Fatima Hospital, Taegu (Korea); Kim, O. B.; Lee, H. J.; Won, C. H. [Keimyung Univ., Taegu (Korea); Yoon, S. M. [Dong-a Univ., Pusan (Korea)

    2000-04-01

    To design and fabricate of the high dose rate source and applicators which are tandem, ovoids and colpostat for OB/Gyn brachytherapy includes the computerized dose planning system. Designed the high dose rate Ir-192 source with nuclide atomic power irradiation and investigated the dose characteristics of fabricated brachysource. We performed the effect of self-absorption and determining the gamma constant and output factor and determined the apparent activity of designed source. he automated computer planning system provided the 2D distribution and 3D includes analysis programs. Created the high dose rate source Ir-192, 10 Ci(370GBq). The effective attenuation factor from the self-absorption and source wall was examined to 0.55 of the activity of bare source and this factor is useful for determination of the apparent activity and gamma constant 4.69 Rcm{sup 2}/mCi-hr. Fabricated the colpostat was investigated the dose distributions of frontal, axial and sagittal plane in intra-cavitary radiation therapy for cervical cancer. The reduce dose at bladder and rectum area was found about 20 % of original dose. The computerized brachytherapy planning system provides the 2-dimensional isodose and 3-D include the dose-volume histogram(DVH) with graphic-user-interface mode. emoted afterloading device was built for experiment of created Ir-192 source with film dosimetry within {+-}1 mm discrepancy. 34 refs., 25 figs., 11 tabs. (Author)

  7. High-dose calcium stimulation test in a case of insulinoma masquerading as hysteria.

    Science.gov (United States)

    Nakamura, Yoshio; Doi, Ryuichiro; Kohno, Yasuhiro; Shimono, Dai; Kuwamura, Naomitsu; Inoue, Koichi; Koshiyama, Hiroyuki; Imamura, Masayuki

    2002-11-01

    It is reported that some cases with insulinoma present with neuropsychiatric symptoms and are often misdiagnosed as psychosis. Here we report a case of insulinoma masquerading as hysteria, whose final diagnosis could be made using high-dose calcium stimulation test. A 28-yr-old woman was referred presenting with substupor, mutism, mannerism, restlessness, and incoherence. Laboratory examinations revealed hypoglycemia (33 mg/dL) and detectable insulin levels (9.7 microU/mL), suggesting the diagnosis of insulinoma. However, neither imaging studies nor selective arterial calcium injection (SACI) test with a conventional dose of calcium (0.025 mEq/kg) indicated the tumor. High-dose calcium injection (0.05 mEq/kg) evoked insulin secretion when injected into superior mesenteric artery. A solitary tumor in the head of the pancreas was resected, and her plasma glucose returned to normal. Postoperatively, iv injection of secretin resulted in a normal response of insulin, which was not found preoperatively. This case suggests the usefulness of the SACI test with high-dose of calcium in the case of insulinoma when the standard dose fails to detect such a tumor.

  8. Base of skull and cervical spine chordomas in children treated by high-dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Benk, Veronique; Liebsch, Norbert J; Munzenrider, John E; Efird, John; McManus, Patricia; Suit, Herman

    1995-02-01

    Purpose: To evaluate the outcome of children with base of skull or cervical spine chordomas treated by high dose irradiation. Methods and Materials: Eighteen children, 4 to 18 years of age, with base of skull or cervical spine chordomas, received fractionated high-dose postoperative radiation using mixed photon and 160 MeV proton beams. The median tumor dose was 69 Cobalt Gray-equivalent (CGE) with a 1.8 CGE daily fraction. Results: The median follow-up was 72 months. The 5-year actuarial survival was 68% and the 5-year disease-free survival (DFS) was 63%. The only significant prognostic factor was the location: patients with cervical spine chordomas had a worse survival than those with base of skull lesions (p = 0.008). The incidence of treatment-related morbidity was acceptable: two patients developed a growth hormone deficit corrected by hormone replacement, one temporal lobe necrosis, and one fibrosis of the temporalis muscle, improved by surgery. Conclusion: Chordomas in children behave similarly to those in adults: children can receive the same high-dose irradiation as adults with acceptable morbidity.

  9. The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration.

    Science.gov (United States)

    Schlienz, Nicolas J; Lee, Dustin C; Stitzer, Maxine L; Vandrey, Ryan

    2018-06-01

    There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users. Non-treatment seeking daily cannabis users (N = 13) completed a residential within-subjects crossover study and were administered placebo, low-dose dronabinol (120 mg/day; 40 mg tid), or high-dose dronabinol (180-240 mg/day; 60-80 mg tid) for 12 consecutive days (order counterbalanced). During each 12-day dronabinol maintenance phase, participants were allowed to self-administer smoked cannabis containing <1% THC (placebo) or 5.7% THC (active) under forced-choice (drug vs. money) or progressive ratio conditions. Participants self-administered significantly more active cannabis compared with placebo in all conditions. When active cannabis was available, self-administration was significantly reduced during periods of dronabinol maintenance compared with placebo maintenance. There was no difference in self-administration between the low- and high-dose dronabinol conditions. Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine.

    Science.gov (United States)

    Babaei-Jadidi, Roya; Karachalias, Nikolaos; Ahmed, Naila; Battah, Sinan; Thornalley, Paul J

    2003-08-01

    Accumulation of triosephosphates arising from high cytosolic glucose concentrations in hyperglycemia is the trigger for biochemical dysfunction leading to the development of diabetic nephropathy-a common complication of diabetes associated with a high risk of cardiovascular disease and mortality. Here we report that stimulation of the reductive pentosephosphate pathway by high-dose therapy with thiamine and the thiamine monophosphate derivative benfotiamine countered the accumulation of triosephosphates in experimental diabetes and inhibited the development of incipient nephropathy. High-dose thiamine and benfotiamine therapy increased transketolase expression in renal glomeruli, increased the conversion of triosephosphates to ribose-5-phosphate, and strongly inhibited the development of microalbuminuria. This was associated with decreased activation of protein kinase C and decreased protein glycation and oxidative stress-three major pathways of biochemical dysfunction in hyperglycemia. Benfotiamine also inhibited diabetes-induced hyperfiltration. This was achieved without change in elevated plasma glucose concentration and glycated hemoglobin in the diabetic state. High-dose thiamine and benfotiamine therapy is a potential novel strategy for the prevention of clinical diabetic nephropathy.

  11. Rectal dose assessment in patients submitted to high-dose-rate brachytherapy for uterine cervix cancer

    International Nuclear Information System (INIS)

    Oliveira, Jetro Pereira de; Batista, Delano Valdivino Santos; Bardella, Lucia Helena; Carvalho, Arnaldo Rangel

    2009-01-01

    Objective: The present study was aimed at developing a thermoluminescent dosimetric system capable of assessing the doses delivered to the rectum of patients submitted to high-dose-rate brachytherapy for uterine cervix cancer. Materials and methods: LiF:Mg,Ti,Na powder was the thermoluminescent material utilized for evaluating the rectal dose. The powder was divided into small portions (34 mg) which were accommodated in a capillary tube. This tube was placed into a rectal probe that was introduced into the patient's rectum. Results: The doses delivered to the rectum of six patients submitted to high-dose-rate brachytherapy for uterine cervix cancer evaluated by means of thermoluminescent dosimeters presented a good agreement with the planned values based on two orthogonal (anteroposterior and lateral) radiographic images of the patients. Conclusion: The thermoluminescent dosimetric system developed in the present study is simple and easy to be utilized as compared to other rectal dosimetry methods. The system has shown to be effective in the evaluation of rectal doses in patients submitted to high-dose-rate brachytherapy for uterine cervix cancer. (author)

  12. False-positive buprenorphine EIA urine toxicology results due to high dose morphine: a case report.

    Science.gov (United States)

    Tenore, Peter L

    2012-01-01

    In monitoring a patient with chronic pain who was taking high-dose morphine and oxycodone with weekly urine enzymatic immunoassay (EIA) toxicology testing, the authors noted consistent positives for buprenorphine. The patient was not taking buprenorphine, and gas chromatography/mass spectroscopy (GCMS) testing on multiple samples revealed no buprenorphine, indicating a case of false-positive buprenorphine EIAs in a high-dose opiate case. The authors discontinued oxycodone for a period of time and then discontinued morphine. Urine monitoring with EIAs and GCMS revealed false-positive buprenorphine EIAs, which remained only when the patient was taking morphine. When taking only oxycodone and no morphine, urine samples became buprenorphine negative. When morphine was reintroduced, false-positive buprenorphine results resumed. Medical practitioners should be aware that high-dose morphine (with morphine urine levels turning positive within the 15,000 to 28,000 mg/mL range) may produce false-positive buprenorphine EIAs with standard urine EIA toxicology testing.

  13. Extra-high doses detected in the enamel of human teeth in the Techa riverside region

    Energy Technology Data Exchange (ETDEWEB)

    Shishkina, E.A., E-mail: ElenaA.Shishkina@gmail.com [Urals Research Center for Radiation Medicine, 68A, Vorovsky Str., 454076 Chelyabinsk (Russian Federation); Degteva, M.O.; Tolstykh, E.I.; Volchkova, A. [Urals Research Center for Radiation Medicine, 68A, Vorovsky Str., 454076 Chelyabinsk (Russian Federation); Ivanov, D.V. [Institute of Metal Physics, Russian Academy of Sciences, 18 S. Kovalevsky Str, 620041 Yekaterinburg (Russian Federation); Wieser, A. [Helmholtz Zentrum Muenchen, German Research Centre for Environmental Health, D-85764 Neuherberg (Germany); Della Monaca, S. [Istituto Superiore di Sanita, 00161 Rome (Italy); Istituto Regina Elena, 00144 Rome (Italy); Fattibene, P. [Istituto Superiore di Sanita, 00161 Rome (Italy); Istituto Nazionale di Fisica Nucleare, 00161 Rome (Italy)

    2011-09-15

    During the long-term study of tooth enamel by EPR dosimetry for population exposed to radiation due to contamination of the Techa River, it was found out that for some of the tooth donors the dose accumulated in tooth enamel could be as high as several tens of Gy. Such doses were absorbed only in tooth enamel and they should not be associated with exposures to other organs or the whole body. The nature of such doses was discussed in a number of previous papers where it was shown that the source of such doses is {sup 90}Sr incorporated in the calcified dental tissues. However, among specialists in radiation dosimetry who were not involved in the biokinetic studies, the nature and dosimetric significance of extra-high doses in tooth enamel are still raising questions. The aim of the current paper is to summarize the accumulated information on extra-high doses in the teeth of the Techa riverside residents, describe the dose levels observed, explain the nature of extra-high doses in the enamel and discuss their informative value. The paper includes an overview of already published findings and an analysis of information collected in the data bank of the Urals Research Center for Radiation Medicine (URCRM), Chelyabinsk, Russia, which has not been published before.

  14. Base of skull and cervical spine chordomas in children treated by high-dose irradiation

    International Nuclear Information System (INIS)

    Benk, Veronique; Liebsch, Norbert J.; Munzenrider, John E.; Efird, John; McManus, Patricia; Suit, Herman

    1995-01-01

    Purpose: To evaluate the outcome of children with base of skull or cervical spine chordomas treated by high dose irradiation. Methods and Materials: Eighteen children, 4 to 18 years of age, with base of skull or cervical spine chordomas, received fractionated high-dose postoperative radiation using mixed photon and 160 MeV proton beams. The median tumor dose was 69 Cobalt Gray-equivalent (CGE) with a 1.8 CGE daily fraction. Results: The median follow-up was 72 months. The 5-year actuarial survival was 68% and the 5-year disease-free survival (DFS) was 63%. The only significant prognostic factor was the location: patients with cervical spine chordomas had a worse survival than those with base of skull lesions (p = 0.008). The incidence of treatment-related morbidity was acceptable: two patients developed a growth hormone deficit corrected by hormone replacement, one temporal lobe necrosis, and one fibrosis of the temporalis muscle, improved by surgery. Conclusion: Chordomas in children behave similarly to those in adults: children can receive the same high-dose irradiation as adults with acceptable morbidity

  15. High dose per fraction dosimetry of small fields with Gafchromic EBT2 film

    International Nuclear Information System (INIS)

    Hardcastle, Nicholas; Basavatia, Amar; Bayliss, Adam; Tome, Wolfgang A.

    2011-01-01

    Purpose: Small field dosimetry is prone to uncertainties due to the lack of electronic equilibrium and the use of the correct detector size relative to the field size measured. It also exhibits higher sensitivity to setup errors as well as large variation in output with field size and shape. Radiochromic film is an attractive method for reference dosimetry in small fields due to its ability to provide 2D dose measurements while having minimal impact on the dose distribution. Gafchromic EBT2 has a dose range of up to 40 Gy; therefore, it could potentially be useful for high dose reference dosimetry with high spatial resolution. This is a requirement in stereotactic radiosurgery deliveries, which deliver high doses per fraction to small targets. Methods: Targets of 4 mm and 12 mm diameters were treated to a minimum peripheral dose of 21 Gy prescribed to 80% of the maximum dose in one fraction. Target doses were measured with EBT2 film (both targets) and an ion chamber (12 mm target only). Measured doses were compared with planned dose distributions using profiles through the target and minimum peripheral dose coverage. Results: The measured target doses and isodose coverage agreed with the planned dose within ±1 standard deviation of three measurements, which were 2.13% and 2.5% for the 4 mm and 12 mm targets, respectively. Conclusions: EBT2 film is a feasible dosimeter for high dose per fraction reference 2D dosimetry.

  16. High-dose ascorbic acid decreases cholesterolemic factors of an atherogenic diet in guinea pigs.

    Science.gov (United States)

    Filis, Konstantinos; Anastassopoulou, Aikaterini; Sigala, Fragiska; Theodorou, Dimitrios; Manouras, Andreas; Leandros, Emanouel; Sigalas, Panagiotis; Hepp, Wolfgang; Bramis, John

    2007-03-01

    The study evaluates the effect of a high supplemental dose of ascorbic acid (AA) on plasma concentrations of total cholesterol (TC), triglycerides (TG), total lipids (TL), and lipoprotein fractions high-density, very-low-density-, and low-density lipoprotein (HDL, VLDL, LDL) in guinea pigs fed with atherogenic diet. Group I consisted of 5 normally fed guinea pigs plus a low dose of AA (1 mg/100 g/day), group II consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a low dose of AA (1 mg/100 g/day), and group III consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a high dose of AA (30 mg/100 g/day). Cholesterolemic factors concentrations were determined after nine weeks. Concentrations of TC, TG, TL, LDL, and VLDL were increased in group II compared to group I (p < 0.01 for all differences). Supplementation with a high dose of AA resulted in decreased concentrations of TC (p < 0.01), TG (p < 0.01), TL (p < 0.01), and LDL (p < 0.01) in group III compared to group II. Additionally, concentration of HDL was increased in group III compared to group II (p < 0.01). High-dose AA supplementation to an atherogenic diet decreases concentrations of TC, TG, TL, and LDL and increases concentration of HDL compared to low-dose AA.

  17. Image-Guided Stereotactic Radiosurgery Using a Specially Designed High-Dose-Rate Linac

    International Nuclear Information System (INIS)

    Bayouth, John E.; Kaiser, Heather S.; Smith, Mark C.; Pennington, Edward C.; Anderson, Kathleen M. C.; Ryken, Timothy C.; Buatti, John M.

    2007-01-01

    Stereotactic radiosurgery and image-guided radiotherapy (IGRT) place enhanced demands on treatment delivery machines. In this study, we describe a high-dose-rate output accelerator as a part of our stereotactic IGRT delivery system. The linac is a Siemens Oncor without a flattening filter, and enables dose rates to reach 1000 monitor units (MUs) per minute. Even at this high-dose-rate, the linac dosimetry system remains robust; constancy, linearity, and beam energy remain within 1% for 3 to 1000 MU. Dose profiles for larger field sizes are not flat, but they are radially symmetric and, as such, able to be modeled by a treatment planning system. Target localization is performed via optical guidance utilizing a 3-dimensional (3D) ultrasound probe coupled to an array of 4 infrared light-emitting diodes. These diodes are identified by a fixed infrared camera system that determines diode position and, by extension, all objects imaged in the room coordinate system. This system provides sub-millimeter localization accuracy for cranial applications and better than 1.5 mm for extracranial applications. Because stereotactic IGRT can require significantly longer times for treatment delivery, the advantages of the high-dose-rate design and its direct impact on IGRT are discussed

  18. Myocardial protection induced by fentanyl in pigs exposed to high-dose adrenaline.

    Science.gov (United States)

    da Luz, Vinicius Fernando; Otsuki, Denise Aya; Gonzalez, Maria Margarita Castro; Negri, Elnara Marcia; Caldini, Elia Garcia; Damaceno-Rodrigues, Nilsa Regina; Malbouisson, Luiz Marcelo Sá; Viana, Bruno Gonçalves; Vane, Matheus Fachini; Carmona, Maria Jose Carvalho

    2015-10-01

    The use of high doses of adrenaline is common in critical patients, especially during cardiac arrest. During these situations, myocardial dysfunction can be a result of multiple factors, including adrenaline use. In addition, opioids have been shown to have anti-arrhythmic and anti-ischemic mechanisms that may confer cardiac protection. This study aimed to evaluate the effects of fentanyl on myocardial function in pigs exposed to high-dose adrenaline. After institutional ethics committee approval, 26 pigs were randomly allocated to receive either 20 μg/kg fentanyl (n = 10; fentanyl group) administered 5 min before five doses of adrenaline (20 μg/kg), equivalent-volume saline (n = 10; saline group) using the same adrenaline dosing protocol, or neither fentanyl nor adrenaline (n = 6; sham group). The fentanyl group showed lower levels of troponin at the end of the sixth hour compared with the saline group (1.91 ± 1.47 vs 5.44 ± 5.35 ng/mL, P = 0.019). Transmission electron microscopy and immunohistochemistry also showed less myocardial injury in the fentanyl group. The conclusion was reached that fentanyl attenuates myocardial injury caused by high-dose adrenaline without blunting the hemodynamic effect of adrenaline. © 2015 Wiley Publishing Asia Pty Ltd.

  19. Hyperthermia and chemotherapy agent

    International Nuclear Information System (INIS)

    Roizin-Towle, L.; Hall, E.J.

    1981-01-01

    The use of chemotherapeutic agents for the treatment of cancer dates back to the late 19th century, but the modern era of chemotherapy drugs was ushered in during the 1940's with the development of the polyfunctional alkylating agent. Since then, numerous classes of drugs have evolved and the combined use of antineoplastic agents with other treatment modalities such as radiation or heat, remains a large relatively unexplored area. This approach, combining local hyperthermia with chemotherapy agents affords a measure of targeting and selective toxicity not previously available for drugs. In this paper, the effects of adriamycin, bleomycin and cis-platinum are examined. The adjuvant use of heat may also reverse the resistance of hypoxic cells noted for some chemotherapy agents

  20. Combination Chemotherapy for Influenza

    Directory of Open Access Journals (Sweden)

    Robert G. Webster

    2010-07-01

    Full Text Available The emergence of pandemic H1N1 influenza viruses in April 2009 and the continuous evolution of highly pathogenic H5N1 influenza viruses underscore the urgency of novel approaches to chemotherapy for human influenza infection. Anti-influenza drugs are currently limited to the neuraminidase inhibitors (oseltamivir and zanamivir and to M2 ion channel blockers (amantadine and rimantadine, although resistance to the latter class develops rapidly. Potential targets for the development of new anti-influenza agents include the viral polymerase (and endonuclease, the hemagglutinin, and the non-structural protein NS1. The limitations of monotherapy and the emergence of drug-resistant variants make combination chemotherapy the logical therapeutic option. Here we review the experimental data on combination chemotherapy with currently available agents and the development of new agents and therapy targets.

  1. Chemotherapy in thyroid carcinoma

    International Nuclear Information System (INIS)

    Samuel, A.M.; Shah, D.H.

    1999-01-01

    Chemotherapy alone, either as a single drug or a combination of drugs with or without external radiation (ER) is useful for treatment of locally advanced disease and non iodine concentrating metastasis in differentiated thyroid cancers (DTC). The reported response is not encouraging, but the absence of better alternatives leave no choice for the treatment of such cases. However, for treatment of anaplastic thyroid cancers (ANC), chemotherapy (CT) in combination with ER results in local control. In medullary thyroid cancers (MTC), the results obtained with multimodal treatment are encouraging

  2. Extravasation of chemotherapy

    DEFF Research Database (Denmark)

    Langer, Seppo W

    2010-01-01

    Extravasation of chemotherapy is a feared complication of anticancer therapy. The accidental leakage of cytostatic agents into the perivascular tissues may have devastating short-term and long-term consequences for patients. In recent years, the increased focus on chemotherapy extravasation has led...... to the development of international guidelines that have proven useful tools in daily clinical practice. Moreover, the tissue destruction in one of the most dreaded types of extravasation (ie, anthracycline extravasation) now can effectively be prevented with a specific antidote, dexrazoxane....

  3. Chemotherapy-induced polyneuropathy

    DEFF Research Database (Denmark)

    Zedan, Ahmed; Vilholm, Ole Jakob

    2014-01-01

    Chemotherapy-induced polyneuropathy (CIPN) is a common, but underestimated, clinical challenge. Incidence varies depending on many factors that are equally as important as the type of chemotherapeutic agent itself. Moreover, the assessment of CIPN is still uncertain, as several of the most...... frequently used scales do not rely on a formal neurological evaluation and depend on patients' reports and examiners' interpretations. Therefore, the aim of this MiniReview was to introduce the most common chemotherapies that cause neuropathy, and in addition to this, highlight the most significant...

  4. Treatment with high dose of erythropoiesis-stimulating agents and mortality: analysis with a sequential Cox approach and a marginal structural model

    NARCIS (Netherlands)

    Suttorp, Marit M.; Hoekstra, Tiny; Mittelman, Moshe; Ott, Ilka; Krediet, Raymond T.; Dekker, Friedo W.; Putter, Hein

    2015-01-01

    Anemia-correction trials indicated higher mortality rates in chronic kidney disease patients assigned to higher hemoglobin targets. The safety of the high erythropoiesis-stimulating agent (ESA) doses that these patients received has therefore been questioned. However, no trial that directly compares

  5. High-dose chemoradiotherapy and watchful waiting for distal rectal cancer

    DEFF Research Database (Denmark)

    Appelt, Ane L; Pløen, John; Harling, Henrik

    2015-01-01

    -dose radiotherapy with concomitant chemotherapy followed by observation (watchful waiting) was successful for non-surgical management of low rectal cancer. METHODS: Patients with primary, resectable, T2 or T3, N0-N1 adenocarcinoma in the lower 6 cm of the rectum were given chemoradiotherapy (60 Gy in 30 fractions...

  6. The effects of sequence and type of chemotherapy and radiation therapy on cosmesis and complications after breast conservation therapy

    International Nuclear Information System (INIS)

    Markiewicz, Deborah A.; Schultz, Delray J.; Haas, Jonathan A.; Harris, Eleanor E. R.; Fox, Kevin R.; Glick, John H.; Solin, Lawrence J.

    1996-01-01

    Purpose: Chemotherapy plays an increasingly important role in the treatment of both node-negative and node-positive breast cancer patients, but the optimal sequencing of chemotherapy and radiation therapy is not well established. The purpose of this study is to evaluate the interaction of sequence and type of chemotherapy and hormonal therapy given with radiation therapy on the cosmetic outcome and the incidence of complications of Stage I and II breast cancer patients treated with breast-conserving therapy. Methods and Materials: The records of 1053 Stage I and II breast cancer patients treated with curative intent with breast-conserving surgery, axillary dissection, and radiation therapy between 1977-1991 were reviewed. Median follow-up after treatment was 6.7 years. Two hundred fourteen patients received chemotherapy alone, 141 patients received hormonal therapy alone, 86 patients received both, and 612 patients received no adjuvant therapy. Patients who received chemotherapy ± hormonal therapy were grouped according to sequence of chemotherapy: (a) concurrent = concurrent chemotherapy with radiation therapy followed by chemotherapy; (b) sequential = radiation followed by chemotherapy or chemotherapy followed by radiation; and (c) sandwich = chemotherapy followed by concurrent chemotherapy and radiation followed by chemotherapy. Compared to node negative patients, node-positive patients more commonly received chemotherapy (77 vs. 9%, p < 0.0001) and/or hormonal therapy (40 vs. 14%, p < 0.0001). Among patients who received chemotherapy, the majority (243 patients) received concurrent chemotherapy and radiation therapy with two cycles of cytoxan and 5-fluorouracil (5-FU) administered during radiation followed by six cycles of chemotherapy with cytoxan, 5-fluorouracil and either methotrexate(CMF) or doxorubicin(CAF). For analysis of cosmesis, patients included were relapse free with 3 years minimum follow-up. Results: The use of chemotherapy had an adverse effect

  7. Chemotherapy-induced hypocalcemia.

    Science.gov (United States)

    Ajero, Pia Marie E; Belsky, Joseph L; Prawius, Herbert D; Rella, Vincent

    2010-01-01

    To present a unique case of transient, asymptomatic chemotherapy-induced hypocalcemia not attributable to hypomagnesemia or tumor lysis syndrome and review causes of hypocalcemia related to cancer with and without use of chemotherapy. We present a case detailing the clinical and laboratory findings of a patient who had severe hypocalcemia during chemotherapy and discuss causes of hypocalcemia with an extensive literature review of chemotherapeutic agents associated with this biochemical abnormality. In a 90-year-old man, hypocalcemia developed during 2 courses of chemotherapy for Hodgkin lymphoma, with partial recovery between courses and normal serum calcium 10 months after completion of treatment. Magnesium, vitamin D, and parathyroid hormone levels were low normal. There was no evidence of tumor lysis syndrome. Of the various agents administered, vinca alkaloids seemed the most likely cause. Serial testing suggested that the underlying mechanism may have been acquired, reversible hypoparathyroidism. No other similar case was found in the published literature. The severe hypocalcemia in our patient could not be attributed to hypomagnesemia or tumor lysis syndrome, and it was clearly associated with the timing of his chemotherapeutic regimen. Possibilities include direct parathyroid hormone suppression or alteration of calcium sensing by the chemotherapeutic drugs. Serum calcium surveillance before and during chemotherapeutic management of cancer patients may reveal more instances and provide insight into the exact mechanism of this lesser known yet striking complication.

  8. After chemotherapy - discharge

    Science.gov (United States)

    You had chemotherapy treatment for your cancer. Your risk of infection, bleeding, and skin problems may be high. You may have mouth sores, an upset stomach, and diarrhea. You will probably get tired easily. Your appetite may be poor, but you should be able ...

  9. Adjuvant endocrine and chemotherapy for early breast cancer

    International Nuclear Information System (INIS)

    Henderson, I. Craig

    1996-01-01

    Objective: Present the results of the 1995 World Overview which will be held in Oxford England two weeks before ASTRO. Discuss the interpretation and application of these results. Review current research topics on the use of adjuvant endocrine and chemotherapy for early breast cancer. The survival benefits from adjuvant chemotherapy in premenopausal women and adjuvant tamoxifen in postmenopausal women are well established. Each will reduce the annual odds of death by about 25% resulting in a 10 year survival difference of 8-10%. By the time of this presentation, the results of the 1995 Adjuvant Therapy Overview should be with 10+ years of follow-up, and if possible these will be summarized. Current efforts to improve on previous results are focused on the following areas: Optimal chemotherapy dose. Decreasing dose will compromise patient survival. It is not as certain that increasing dose will have as much impact in improving survival. The NSABP was unable to demonstrate an improvement in survival by modestly increasing the dose of cyclophosphamide alone. However, recent results of a Canadian study of CEF (cyclophosphamide, epidoxorubicin, and 5-fluorouracil) and an Intergroup trial of an intense 16 week polychemotherapy program keep alive the possibility that dose escalation is still a very important question. An NSABP trial evaluating even greater cyclophosphamide dose escalation, an Intergroup evaluation of different doxorubicin doses, and two Intergroup trials evaluating very high dose chemotherapy and bone marrow transplantation should provide definitive evidence regarding the importance of dose. Drug sequence. A study from Milan suggests that initial treatment with single agent doxorubicin followed by CMF will be superior to alternating doxorubicin and CMF. This has not been confirmed yet, and the reason for increased benefit from such a sequence is not entirely clear. This concept is being explored further in an Intergroup trial comparing four cycles of

  10. Remarks on sequential designs in risk assessment

    International Nuclear Information System (INIS)

    Seidenfeld, T.

    1982-01-01

    The special merits of sequential designs are reviewed in light of particular challenges that attend risk assessment for human population. The kinds of ''statistical inference'' are distinguished and the problem of design which is pursued is the clash between Neyman-Pearson and Bayesian programs of sequential design. The value of sequential designs is discussed and the Neyman-Pearson vs. Bayesian sequential designs are probed in particular. Finally, warnings with sequential designs are considered, especially in relation to utilitarianism

  11. Calibration procedure for thermoluminescent dosemeters in water absorbed doses for Iridium-192 high dose rate sources

    International Nuclear Information System (INIS)

    Reyes Cac, Franky Eduardo

    2004-10-01

    Thermoluminescent dosimeters are used in brachytherapy services quality assurance programs, with the aim of guaranteeing the correct radiation dose supplied to cancer patients, as well as with the purpose of evaluating new clinical procedures. This work describes a methodology for thermoluminescent dosimeters calibration in terms of absorbed dose to water for 192 Ir high dose rate sources. The reference dose used is measured with an ionization chamber previously calibrated for 192 Ir energy quality, applying the methodology proposed by Toelli. This methodology aims to standardizing the procedure, in a similar form to that used for external radiotherapy. The work evolves the adaptation of the TRS-277 Code of the International Atomic Energy Agency, for small and big cavities, through the introduction for non-uniform experimental factor, for the absorbed dose in the neighborhood of small brachytherapy sources. In order to simulate a water medium around the source during the experimental work, an acrylic phantom was used. It guarantees the reproducibility of the ionization chamber and the thermoluminescent dosimeter's location in relation to the radiation source. The values obtained with the ionization chamber and the thermoluminescent dosimeters, exposed to a 192 Ir high dose rate source, were compared and correction factors for different source-detector distances were determined for the thermoluminescent dosimeters. A numeric function was generated relating the correction factors and the source-detector distance. These correction factors are in fact the thermoluminescent dosimeter calibration factors for the 192 Ir source considered. As a possible application of this calibration methodology for thermoluminescent dosimeters, a practical range of source-detector distances is proposed for quality control of 192 Ir high dose rate sources. (author)

  12. Development of radiation fusion technology with food technology by the application of high dose irradiation

    International Nuclear Information System (INIS)

    Lee, Juwoon; Kim, Jaehun; Choi, Jongil

    2012-04-01

    This study was performed to achieve stable food supply and food safety with radiation fusion technology as a preparation for food weaponization. Results at current stage are following: First, for the development of radiation and food engineering fusion technology using high dose irradiation, the effects of high dose irradiation on food components were evaluated. The combination treatment of irradiation with food engineering was developed. Irradiation condition to destroy radiation resistant foodborne bacteria were determined. Second, for the development of E-beam irradiation technology, the effects of radiation sources on food compounds, processing conditions, and food quality of final products were compared. Food processing conditions for agricultural/aquatic products with different radiation sources was developed and the domination of E-beam irradiation foods were determined. The physical marker for E-beam irradiated foods or not was developed. Third, for the fundamental researches to develop purposed foods to extreme environmental, ready-to-eat foods were developed using high dose irradiation. Food processing for export strategy foods such as process ginseng were developed. Food processing with irradiation to destroy mycotoxin and to inhibit production of mycotoxin was developed. Mathematical models to predict necessary irradiation doses and radiation sources were developed and validated. Through the fundamental researches, the legislation for irradiation approval on meat products, sea foods and dried sea foods, and use of E-beam was introduced. Results from this research project, the followings are expected. Improvement of customer acceptance and activation of irradiation technology by the use of various irradiation rays. Increase of indirect food productivity, and decrease of SOC and improvement of public health by prevention of foodborne outbreaks. Build of SPS/TBT system against imported products and acceleration of domestic product export. Systemized

  13. Development of Radiation Fusion Technology with Food Technology by the Application of High Dose Irradiation

    International Nuclear Information System (INIS)

    Kim, Ju Won; Kim, Jae Hun; Choi, Jong Il

    2010-04-01

    This study was studied to achieve stable food supply and food safety with radiation fusion technology as a preparation for food weaponization. Results at current stage are following: First, for the development of radiation and food engineering fusion technology using high dose irradiation, the effects of high dose irradiation on food components were evaluated. The combination treatment of irradiation with food engineering were developed. Irradiation condition to destroy radiation resistant food borne bacteria were determined. Second, for the development of E-beam irradiation technology, the effects of radiation sources on food compounds, processing conditions, and food quality of final products were compared. Food processing conditions for agricultural/aquatic products with different radiation sources were developed and the domination of E-beam irradiation foods were determined. The physical marker for E-beam irradiated foods or not were developed. Third, for the fundamental researches to develop purposed foods to extreme environmental, ready-to-eat foods were developed using high dose irradiation. Food processing for export strategy foods such as process ginseng were developed. Food processing with irradiation to destroy mycotoxin and to inhibit production of mycotoxin were developed. Mathematical models to predict necessary irradiation doses and radiation sources were developed and validated. Through the fundamental researches, the legislation for irradiation approval on meat products, sea foods and dried sea foods, and use of E-beam were introduced. Results from this research project, the followings are expected. (1) Improvement of customer acceptance and activation of irradiation technology by the use of various irradiation rays. (2) Increase of indirect food productivity, and decrease of SOC and improvement of public health by prevention of food borne outbreaks. (3) Build of SPS/TBT system against imported products and acceleration of domestic product export

  14. Does perioperative high-dose prednisolone have clinical benefits for generalized myasthenia gravis?

    Science.gov (United States)

    Sekine, Yasuo; Kawaguchi, Naoki; Hamada, Chikuma; Sekiguchi, Hiromi; Yasufuku, Kazuhiro; Iyoda, Akira; Shibuya, Kiyoshi; Fujisawa, Takehiko

    2006-06-01

    The purpose of this study was to clarify the clinical benefits of perioperative administration of high-dose prednisolone (PSL) combined with extended thymectomy on the long-term outcomes of 116 consecutive patients with generalized myasthenia gravis (MG). A retrospective review was conducted on 116 patients diagnosed with generalized MG who received alternate-day oral administration of high-dose PSL (100 mg/alternate days) and had undergone transsternal extended thymectomy. Incidences of postoperative myasthenic crisis, adverse effects of steroid, long-term outcomes, such as complete stable remission (CSR), pharmacologic remission (PR) or improvement (Imp), and disease recurrence after CSR were evaluated. Six patients (5.2%) experienced post-thymectomy myasthenic crisis. Crude cumulative CSR and PR + CSR rates were 44.8 and 62.7%, respectively. Life table analysis showed that 41.8, 52.8 and 63.4% of the patients were in CSR at 3, 5 and 10 years, respectively. Multivariate analysis revealed that age and pretreatment classification according to the Myasthenia Gravis Foundation of America (MGFA) criteria tended to be independent predictors of CSR. There were 6.9% with compressive vertebral fracture, 13.8% with cataract, and 5.2% with steroid-induced diabetes. Life table analysis revealed that recurrence rates after CSR were 36.8 and 46.0% at 3 and 5 years, respectively. Patients with thymoma had a significantly higher rate of recurrence than those without thymoma (p = 0.001). Alternate-day administration of high-dose prednisolone reduced the risk of post-thymectomy myasthenic crisis. Presence of thymoma was a risk factor for MG recurrence after CSR.

  15. Development of Radiation Fusion Technology with Food Technology by the Application of High Dose Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ju Won; Kim, Jae Hun; Choi, Jong Il

    2010-04-15

    This study was studied to achieve stable food supply and food safety with radiation fusion technology as a preparation for food weaponization. Results at current stage are following: First, for the development of radiation and food engineering fusion technology using high dose irradiation, the effects of high dose irradiation on food components were evaluated. The combination treatment of irradiation with food engineering were developed. Irradiation condition to destroy radiation resistant food borne bacteria were determined. Second, for the development of E-beam irradiation technology, the effects of radiation sources on food compounds, processing conditions, and food quality of final products were compared. Food processing conditions for agricultural/aquatic products with different radiation sources were developed and the domination of E-beam irradiation foods were determined. The physical marker for E-beam irradiated foods or not were developed. Third, for the fundamental researches to develop purposed foods to extreme environmental, ready-to-eat foods were developed using high dose irradiation. Food processing for export strategy foods such as process ginseng were developed. Food processing with irradiation to destroy mycotoxin and to inhibit production of mycotoxin were developed. Mathematical models to predict necessary irradiation doses and radiation sources were developed and validated. Through the fundamental researches, the legislation for irradiation approval on meat products, sea foods and dried sea foods, and use of E-beam were introduced. Results from this research project, the followings are expected. (1) Improvement of customer acceptance and activation of irradiation technology by the use of various irradiation rays. (2) Increase of indirect food productivity, and decrease of SOC and improvement of public health by prevention of food borne outbreaks. (3) Build of SPS/TBT system against imported products and acceleration of domestic product export

  16. Development of radiation fusion technology with food technology by the application of high dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Juwoon; Kim, Jaehun; Choi, Jongil; and others

    2012-04-15

    This study was performed to achieve stable food supply and food safety with radiation fusion technology as a preparation for food weaponization. Results at current stage are following: First, for the development of radiation and food engineering fusion technology using high dose irradiation, the effects of high dose irradiation on food components were evaluated. The combination treatment of irradiation with food engineering was developed. Irradiation condition to destroy radiation resistant foodborne bacteria were determined. Second, for the development of E-beam irradiation technology, the effects of radiation sources on food compounds, processing conditions, and food quality of final products were compared. Food processing conditions for agricultural/aquatic products with different radiation sources was developed and the domination of E-beam irradiation foods were determined. The physical marker for E-beam irradiated foods or not was developed. Third, for the fundamental researches to develop purposed foods to extreme environmental, ready-to-eat foods were developed using high dose irradiation. Food processing for export strategy foods such as process ginseng were developed. Food processing with irradiation to destroy mycotoxin and to inhibit production of mycotoxin was developed. Mathematical models to predict necessary irradiation doses and radiation sources were developed and validated. Through the fundamental researches, the legislation for irradiation approval on meat products, sea foods and dried sea foods, and use of E-beam was introduced. Results from this research project, the followings are expected. Improvement of customer acceptance and activation of irradiation technology by the use of various irradiation rays. Increase of indirect food productivity, and decrease of SOC and improvement of public health by prevention of foodborne outbreaks. Build of SPS/TBT system against imported products and acceleration of domestic product export. Systemized

  17. The biochemical changes of bone collagen after high-dose irradiation

    International Nuclear Information System (INIS)

    Tajiri, Ken

    1980-01-01

    In our clinic, patients with malignant bone tumors have been treated by high-dose irradiation therapy, 10,000-20,000 rads, for primary lesions. In order to study the biochemical changes of normal bone around tumor tissue, especially bone collagen, after high-dose irradiation, the author performed the following experiments. The right knee joint of rabbits was irradiated with either 6,000, 10,000, or 15,000 rads by 60 Co-γ ray. The cortical bone of the right tibial metaphysis was used for analyses and compared with the left tibia of the same rabbit. These studies were followed for one year after the final irradiation. The calcium, phosphorous and collagen contents of irradiated bone were remarkably changed. These data indicate that collagen biosynthesis of irradiated bone was decreased and the calcification was disturbed. An increase in the amount of total soluble collagen and a decrease in the amount of hydroxylysine bound sugar were observed. The ratio of β to α chains of the collagen molecule was also changed by the irradiation. The amount of reducible cross-links per hydroxyproline residue was strikingly increased three months after the final irradiation. These changes were remarkable especially in the 10,000 and 15,000 rads irradiated group and found to be recovered approximately six months to one year after the final irradiation. These findings indicate that high-dose irradiation reduces the stability of bone collagen both with the destruction of sugar bonds of hydroxylysine residues and the replacement of matured collagen matrix to immatured one which contain mostly labile reducible cross-links. (author)

  18. Successfully Managing Impending Skin Necrosis following Hyaluronic Acid Filler Injection, using High-Dose Pulsed Hyaluronidase