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Sample records for hypofractionated radiation induces

  1. Hypofractionation does not increase radiation pneumonitis risk with modern conformal radiation delivery techniques

    DEFF Research Database (Denmark)

    Vogelius, Ivan R; Westerly, David C; Cannon, George M

    2010-01-01

    To study the interaction between radiation dose distribution and hypofractionated radiotherapy with respect to the risk of radiation pneumonitis (RP) estimated from normal tissue complication probability (NTCP) models.......To study the interaction between radiation dose distribution and hypofractionated radiotherapy with respect to the risk of radiation pneumonitis (RP) estimated from normal tissue complication probability (NTCP) models....

  2. Hypofractionated radiation therapy for the treatment of feline facial squamous cell carcinoma; Hypofractionated radiation therapy for the treatment of feline facial squamous cell carcinoma

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    Cunha, S.C.S.; Corgozinho, K.B.; Holguin, P.G.; Ferreira, A.M.R., E-mail: simonecsc@gmail.co [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil); Carvalho, L.A.V. [Coordenacao dos Programas de Pos-Graduacao de Engenharia (COPPE/UFRJ), Rio de Janeiro, RJ (Brazil); Canary, P.C.; Reisner, M. [Hospital Universitario Clementino Fraga Filho (HUCFF/UFRJ), Rio de Janeiro, RJ (Brazil); Pereira, A.N.; Souza, H.J.M. [Universidade Federal Rural do Rio de Janeiro (UFRRJ), Seropedica, RJ (Brazil)

    2010-07-01

    The efficacy of hypofractionated radiation protocol for feline facial squamous cell carcinoma was evaluated. Hypofractionated radiation therapy was applied to five cats showing single or multiple facial squamous cell carcinomas, in a total of ten histologically confirmed neoplastic lesions. Of the lesions, two were staged as T{sub 1}, four as T{sub 2}, two as T{sub 3}, and two as T{sub 4}. The animals were submitted to four radiation fractions from 7.6 to 10 grays each, with one week intervals. The equipment was a linear accelerator with electrons beam. The cats were evaluated weekly during the treatment and 30 and 60 days after the end of the radiation therapy. In this study, 40% of the lesions had complete remission, 40% partial remission, and 20% did not respond to the treatment. Response rates were lower as compared to other protocols previously used. However, hypofractionated radiation protocol was considered safe for feline facial squamous cell carcinoma. (author)

  3. The Role of Hypofractionated Radiation Therapy with Photons, Protons and Heavy Ions for Treating Extracranial Lesions

    Directory of Open Access Journals (Sweden)

    Aaron Michael Laine

    2016-01-01

    Full Text Available Traditionally, the ability to deliver large doses of ionizing radiation to a tumor has been limited by radiation induced toxicity to normal surrounding tissues. This was the initial impetus for the development of conventionally fractionated radiation therapy, where large volumes of healthy tissue received radiation and were allowed the time to repair the radiation damage. However, advances in radiation delivery techniques and image guidance have allowed for more ablative doses of radiation to be delivered in a very accurate, conformal and safe manner with shortened fractionation schemes. Hypofractionated regimens with photons have already transformed how certain tumor types are treated with radiation therapy. Additionally, hypofractionation is able to deliver a complete course of ablative radiation therapy over a shorter period of time compared to conventional fractionation regimens making treatment more convenient to the patient and potentially more cost-effective. Recently there has been an increased interest in proton therapy because of the potential further improvement in dose distributions achievable due to their unique physical characteristics. Furthermore, with heavier ions the dose conformality is increased and in addition there is potentially a higher biological effectiveness compared to protons and photons. Due to the properties mentioned above, charged particle therapy has already become an attractive modality to further investigate the role of hypofractionation in the treatment of various tumors. This review will discuss the rationale and evolution of hypofractionated radiation therapy, the reported clinical success with initially photon and then charged particle modalities, and further potential implementation into treatment regimens going forward.

  4. Radiation-Induced Rib Fractures After Hypofractionated Stereotactic Body Radiation Therapy: Risk Factors and Dose-Volume Relationship

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    Asai, Kaori [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Shioyama, Yoshiyuki, E-mail: shioyama@radiol.med.kyushu-u.ac.jp [Department of Heavy Particle Therapy and Radiation Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Nakamura, Katsumasa; Sasaki, Tomonari; Ohga, Saiji; Nonoshita, Takeshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Yoshitake, Tadamasa [Department of Heavy Particle Therapy and Radiation Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Ohnishi, Kayoko [Department of Radiology, National Center for Global Health and Medicine, Tokyo (Japan); Terashima, Kotaro; Matsumoto, Keiji [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Hirata, Hideki [Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Honda, Hiroshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan)

    2012-11-01

    Purpose: The purpose of this study was to clarify the incidence, the clinical risk factors, and the dose-volume relationship of radiation-induced rib fracture (RIRF) after hypofractionated stereotactic body radiation therapy (SBRT). Methods and Materials: One hundred sixteen patients treated with SBRT for primary or metastatic lung cancer at our institution, with at least 6 months of follow-up and no previous overlapping radiation exposure, were included in this study. To determine the clinical risk factors associated with RIRF, correlations between the incidence of RIRF and the variables, including age, sex, diagnosis, gross tumor volume diameter, rib-tumor distance, and use of steroid administration, were analyzed. Dose-volume histogram analysis was also conducted. Regarding the maximum dose, V10, V20, V30, and V40 of the rib, and the incidences of RIRF were compared between the two groups divided by the cutoff value determined by the receiver operating characteristic curves. Results: One hundred sixteen patients and 374 ribs met the inclusion criteria. Among the 116 patients, 28 patients (46 ribs) experienced RIRF. The estimated incidence of rib fracture was 37.7% at 3 years. Limited distance from the rib to the tumor (<2.0 cm) was the only significant risk factor for RIRF (p = 0.0001). Among the dosimetric parameters used for receiver operating characteristic analysis, the maximum dose showed the highest area under the curve. The 3-year estimated risk of RIRF and the determined cutoff value were 45.8% vs. 1.4% (maximum dose, {>=}42.4 Gy or less), 51.6% vs. 2.0% (V40, {>=}0.29 cm{sup 3} or less), 45.8% vs. 2.2% (V30, {>=}1.35 cm{sup 3} or less), 42.0% vs. 8.5% (V20, {>=}3.62 cm{sup 3} or less), or 25.9% vs. 10.5% (V10, {>=}5.03 cm{sup 3} or less). Conclusions: The incidence of RIRF after hypofractionated SBRT is relatively high. The maximum dose and high-dose volume are strongly correlated with RIRF.

  5. Hypofractionated stereotactic radiation therapy in three to five fractions for vestibular schwannoma

    International Nuclear Information System (INIS)

    Morimoto, Masahiro; Yoshioka, Yasuo; Kotsuma, Tadayuki

    2013-01-01

    The objective of this study was to retrospectively examine the outcomes of hypofractionated stereotactic radiation therapy in three to five fractions for vestibular schwannomas. Twenty-five patients with 26 vestibular schwannomas were treated with hypofractionated stereotactic radiation therapy using a CyberKnife. The vestibular schwannomas of 5 patients were associated with type II neurofibromatosis. The median follow-up time was 80 months (range: 6-167); the median planning target volume was 2.6 cm 3 (0.3-15.4); and the median prescribed dose (≥D90) was 21 Gy in three fractions (18-25 Gy in three to five fractions). Progression was defined as ≥2 mm 3-dimensional post-treatment tumor enlargement excluding transient expansion. Progression or any death was counted as an event in progression-free survival rates, whereas only progression was counted in progression-free rates. The 7-year progression-free survival and progression-free rates were 78 and 95%, respectively. Late adverse events (≥3 months) with grades based on Common Terminology Criteria for Adverse Events, v4.03 were observed in 6 patients: Grade 3 hydrocephalus in one patient, Grade 2 facial nerve disorders in two and Grade 1-2 tinnitus in three. In total, 12 out of 25 patients maintained pure tone averages ≤50 dB before hypofractionated stereotactic radiation therapy, and 6 of these 12 patients (50%) maintained pure tone averages at this level at the final audiometric follow-up after hypofractionated stereotactic radiation therapy. However, gradient deterioration of pure tone average was observed in 11 of these 12 patients. The mean pure tone averages before hypofractionated stereotactic radiation therapy and at the final follow-up for the aforementioned 12 patients were 29.8 and 57.1 dB, respectively. Treating vestibular schwannomas with hypofractionated stereotactic radiation therapy in three to five fractions may prevent tumor progression with tolerable toxicity. However, gradient

  6. Hypofractionated stereotactic radiation therapy in three to five fractions for vestibular schwannoma

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    Morimoto, Masahiro; Yoshioka, Yasuo [Osaka Univ., Graduate School of Medicine, Suita, Osaka (Japan); Kotsuma, Tadayuki [Kinki-chuo Chest Medical Center, Sakai, Osaka (Japan); others, and

    2013-08-15

    The objective of this study was to retrospectively examine the outcomes of hypofractionated stereotactic radiation therapy in three to five fractions for vestibular schwannomas. Twenty-five patients with 26 vestibular schwannomas were treated with hypofractionated stereotactic radiation therapy using a CyberKnife. The vestibular schwannomas of 5 patients were associated with type II neurofibromatosis. The median follow-up time was 80 months (range: 6-167); the median planning target volume was 2.6 cm{sup 3} (0.3-15.4); and the median prescribed dose ({>=}D90) was 21 Gy in three fractions (18-25 Gy in three to five fractions). Progression was defined as {>=}2 mm 3-dimensional post-treatment tumor enlargement excluding transient expansion. Progression or any death was counted as an event in progression-free survival rates, whereas only progression was counted in progression-free rates. The 7-year progression-free survival and progression-free rates were 78 and 95%, respectively. Late adverse events ({>=}3 months) with grades based on Common Terminology Criteria for Adverse Events, v4.03 were observed in 6 patients: Grade 3 hydrocephalus in one patient, Grade 2 facial nerve disorders in two and Grade 1-2 tinnitus in three. In total, 12 out of 25 patients maintained pure tone averages {<=}50 dB before hypofractionated stereotactic radiation therapy, and 6 of these 12 patients (50%) maintained pure tone averages at this level at the final audiometric follow-up after hypofractionated stereotactic radiation therapy. However, gradient deterioration of pure tone average was observed in 11 of these 12 patients. The mean pure tone averages before hypofractionated stereotactic radiation therapy and at the final follow-up for the aforementioned 12 patients were 29.8 and 57.1 dB, respectively. Treating vestibular schwannomas with hypofractionated stereotactic radiation therapy in three to five fractions may prevent tumor progression with tolerable toxicity. However, gradient

  7. Lyman NTCP model analysis of radiation-induced liver disease in hypofractionated conformal radiotherapy for primary liver carcinoma

    International Nuclear Information System (INIS)

    Xu Zhiyong; Zhu Yi; Zhao Jiaodong; Fu Xiaolong; Jiang Guoliang; Liang Shixiong; Zhu Xiaodong

    2006-01-01

    Objective: To identify the factors associated with radiation-induced liver disease (RILD) and to describe the probability of RILD using the Lyman normal tissue complication(NTCP) model for primary liver carcinoma(PLC) treated with hypofractionated conformal therapy (CRT). Methods: A total of 109 PLC patients treated with hypofractionated CRT were prospectively followed according to the Child-Pugh classification for liver cirrhosis, 93 patients in class A and 16 in class B. The mean dose of radiation to the isocenter was (53.5±5.5) Gy, fractions of (4.8±0.5) Gy, with interfraction interval of 48 hours and irradiation 3 times per week. Maximal likelihood analysis yielded the best estimates of parameters of the Lyman NTCP model for all patients; Child-Pugh A and Child-Pugh B patients, respectively. Results: Of all the patients, 17 developed RILD (17/109), 8 in Child-Pugh A (8/93) and 9 in Child-Pugh B (9/16). By multivariate analysis, only the Child-Pugh Grade of liver cirrhosis was the independent factor (P=0.000) associated with the developing of BILD. The best estimates of the NTCP parameters for all 109 patients were n=1.1, m=0.35 and TD 50 (1)=38.5 Gy. The n, m, TD 50 (1) estimated from patients with Child-Pugh A was 1.1, 0.28, 40.5 Gy, respectively, compared with 0.7, 0.43, 23 Gy respectively, for patients with Child-Pugh B. Conclusions: Primary liver cancer patients who possess Child-Pugh B cirrhosis would present a significantly greater susceptibility to RILD after hypofractionated CRT than patients with Child-Pugh A cirrhosis. The predominant risk factor for developing RILD is the severity of hepatic cirrhosis in the liver of PLC patients. (authors)

  8. Whole-Pelvic Nodal Radiation Therapy in the Context of Hypofractionation for High-Risk Prostate Cancer Patients: A Step Forward

    International Nuclear Information System (INIS)

    Kaidar-Person, Orit; Roach, Mack; Créhange, Gilles

    2013-01-01

    Given the low α/β ratio of prostate cancer, prostate hypofractionation has been tested through numerous clinical studies. There is a growing body of literature suggesting that with high conformal radiation therapy and even with more sophisticated radiation techniques, such as high-dose-rate brachytherapy or image-guided intensity modulated radiation therapy, morbidity associated with shortening overall treatment time with higher doses per fraction remains low when compared with protracted conventional radiation therapy to the prostate only. In high-risk prostate cancer patients, there is accumulating evidence that either dose escalation to the prostate or hypofractionation may improve outcome. Nevertheless, selected patients who have a high risk of lymph node involvement may benefit from whole-pelvic radiation therapy (WPRT). Although combining WPRT with hypofractionated prostate radiation therapy is feasible, it remains investigational. By combining modern advances in radiation oncology (high-dose-rate prostate brachytherapy, intensity modulated radiation therapy with an improved image guidance for soft-tissue sparing), it is hypothesized that WPRT could take advantage of recent results from hypofractionation trials. Moreover, the results from hypofractionation trials raise questions as to whether hypofractionation to pelvic lymph nodes with a high risk of occult involvement might improve the outcomes in WPRT. Although investigational, this review discusses the challenging idea of WPRT in the context of hypofractionation for patients with high-risk prostate cancer

  9. Whole-Pelvic Nodal Radiation Therapy in the Context of Hypofractionation for High-Risk Prostate Cancer Patients: A Step Forward

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    Kaidar-Person, Orit [Division of Oncology, Rambam Health Care Campus, Haifa (Israel); Roach, Mack [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Créhange, Gilles, E-mail: gcrehange@cgfl.fr [Department of Radiation Oncology, Georges-François Leclerc Cancer Center, Dijon (France)

    2013-07-15

    Given the low α/β ratio of prostate cancer, prostate hypofractionation has been tested through numerous clinical studies. There is a growing body of literature suggesting that with high conformal radiation therapy and even with more sophisticated radiation techniques, such as high-dose-rate brachytherapy or image-guided intensity modulated radiation therapy, morbidity associated with shortening overall treatment time with higher doses per fraction remains low when compared with protracted conventional radiation therapy to the prostate only. In high-risk prostate cancer patients, there is accumulating evidence that either dose escalation to the prostate or hypofractionation may improve outcome. Nevertheless, selected patients who have a high risk of lymph node involvement may benefit from whole-pelvic radiation therapy (WPRT). Although combining WPRT with hypofractionated prostate radiation therapy is feasible, it remains investigational. By combining modern advances in radiation oncology (high-dose-rate prostate brachytherapy, intensity modulated radiation therapy with an improved image guidance for soft-tissue sparing), it is hypothesized that WPRT could take advantage of recent results from hypofractionation trials. Moreover, the results from hypofractionation trials raise questions as to whether hypofractionation to pelvic lymph nodes with a high risk of occult involvement might improve the outcomes in WPRT. Although investigational, this review discusses the challenging idea of WPRT in the context of hypofractionation for patients with high-risk prostate cancer.

  10. Image Guided Hypofractionated Postprostatectomy Intensity Modulated Radiation Therapy for Prostate Cancer

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    Lewis, Stephen L.; Patel, Pretesh; Song, Haijun [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Freedland, Stephen J. [Surgery Section, Durham Veterans Administration, and Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California (United States); Bynum, Sigrun; Oh, Daniel; Palta, Manisha; Yoo, David; Oleson, James [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Salama, Joseph K., E-mail: joseph.salama@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

    2016-03-01

    Purpose: Hypofractionated radiation therapy (RT) has promising long-term biochemical relapse-free survival (bRFS) with comparable toxicity for definitive treatment of prostate cancer. However, data reporting outcomes after adjuvant and salvage postprostatectomy hypofractionated RT are sparse. Therefore, we report the toxicity and clinical outcomes after postprostatectomy hypofractionated RT. Methods and Materials: From a prospectively maintained database, men receiving image guided hypofractionated intensity modulated RT (HIMRT) with 2.5-Gy fractions constituted our study population. Androgen deprivation therapy was used at the discretion of the radiation oncologist. Acute toxicities were graded according to the Common Terminology Criteria for Adverse Events version 4.0. Late toxicities were scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Biochemical recurrence was defined as an increase of 0.1 in prostate-specific antigen (PSA) from posttreatment nadir or an increase in PSA despite treatment. The Kaplan-Meier method was used for the time-to-event outcomes. Results: Between April 2008 and April 2012, 56 men received postoperative HIMRT. The median follow-up time was 48 months (range, 21-67 months). Thirty percent had pre-RT PSA <0.1; the median pre-RT detectable PSA was 0.32 ng/mL. The median RT dose was 65 Gy (range, 57.5-65 Gy). Ten patients received neoadjuvant and concurrent hormone therapy. Posttreatment acute urinary toxicity was limited. There was no acute grade 3 toxicity. Late genitourinary (GU) toxicity of any grade was noted in 52% of patients, 40% of whom had pre-RT urinary incontinence. The 4-year actuarial rate of late grade 3 GU toxicity (exclusively gross hematuria) was 28% (95% confidence interval [CI], 16%-41%). Most grade 3 GU toxicity resolved; only 7% had persistent grade ≥3 toxicity at the last follow-up visit. Fourteen patients experienced biochemical recurrence at a

  11. Acute radiation dermatitis and pneumonitis in Japanese breast cancer patients with whole breast hypofractionated radiotherapy compared to conventional radiotherapy

    International Nuclear Information System (INIS)

    Osako, Tomo; Oguchi, Masahiko; Kumada, Madoka; Nemoto, Keiko; Iwase, Takuji; Yamashita, Takashi

    2008-01-01

    The objective of this study was to evaluate acute morbidity, radiation dermatitis and pneumonitis, of Japanese patients treated with whole breast hypofractionated radiotherapy (RT) after breast-conserving surgery (BCS), compared to conventional RT. Japanese patients who received whole breast RT after BCS between October 2003 and September 2006 were retrospectively reviewed. Patients who had selected the conventional or hypofractionated schedule received whole breast irradiation of 50 Gy in 25 fractions plus boost or 40 Gy in 16 fractions plus boost. Radiation dermatitis and symptomatic pneumonitis were graded according to the Common Terminology Criteria for Adverse Events version 3.0. Of 443 consecutive patients, 377 (85%) received the conventional schedule and 66 (15%) received the hypofractionated schedule. Of patients treated with the conventional schedule, Grade 0, 1, 2 and 3 radiation dermatitis were observed in 16 (4%), 278 (74%), 77 (20%) and 6 (2%), respectively. Of patients treated with the hypofractionated schedule, Grade 0, 1, 2 and 3 dermatitis were observed in 11 (17%), 49 (74%), 5 (8%) and 1 (1%), respectively. Grade 2-3 dermatitis by the hypofractionated schedule (9%) was observed less frequently than that by the conventional schedule (22%) (chi-square test; P=0.016). Moreover, of patients treated with the conventional schedule, 4 (1%) had Grade 2 radiation pneumonitis. No patient treated with the hypofractionated schedule had symptomatic pneumonitis. Radiation dermatitis and pneumonitis in Japanese patients treated with the hypofractionated schedule is acceptable. Especially, radiation dermatitis by the hypofractionated schedule is milder than that by the conventional schedule. (author)

  12. COMPARISON OF HYPOFRACTIONATED RADIATION THERAPY VERSUS CONVENTIONAL RADIATION THERAPY IN POST MASTECTOMY BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Abhilash

    2016-03-01

    Full Text Available INTRODUCTION Breast cancer is the most common cancer in women worldwide and a leading cause of cancer death in females and accounts for 1.8 million new cases and approximately 0.5 million deaths annually. Patients who present with locally advanced breast cancer (LABC require multidisciplinary team approach that incorporates diagnostic imaging, surgery, chemotherapy and histopathological assessment, including molecular-based studies, radiation, and, if indicated, biologic and hormonal therapies. Hypofractionated radiation therapy following mastectomy has been used in many institutions for several decades and have demonstrated equivalent local control, cosmetic and normal tissues between 50 Gy in 25 fractions and various hypofractionated radiotherapy prescriptions employing 13-16 fractions. Evidence suggests that hypofractionated radiotherapy may also be safe and effective for regional nodal disease. AIMS AND OBJECTIVES To compare the local control and side effects of hypofractionated radiation therapy with conventional radiation therapy in post mastectomy carcinoma breast with stage II and III and to compare the tolerability and compliance of both schedules. MATERIALS AND METHODS The study was conducted on 60 histopathologically proven patients of carcinoma of breast, treated surgically with modified radical mastectomy. Group I patients were given external radiation to chest flap and drainage areas, a dose of 39 Gy/13 fractions/3.1 weeks, a daily dose 3 Gy for 13 fractions in 4 days a week schedule and Group II patients were given external radiation to chest flap and drainage areas, a dose of 50 Gy/25 fractions/5 weeks, to receive a daily dose 2 Gy for 25 fractions in a 5 days a week schedule. RESULTS The median age at presentation in Group I and II was 48 and 50 years respectively. Locoregional control after completion of radiotherapy in Group I vs. Group II was 26/30 (86.7% vs. 27/30 (90% respectively. Acute reactions and their grades in Group

  13. Choosing Wisely? Patterns and Correlates of the Use of Hypofractionated Whole-Breast Radiation Therapy in the State of Michigan

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    Jagsi, Reshma, E-mail: rjagsi@med.umich.edu [University of Michigan, Ann Arbor, Michigan (United States); Griffith, Kent A. [University of Michigan, Ann Arbor, Michigan (United States); Heimburger, David [Munson Medical Center, Traverse City, Michigan (United States); Walker, Eleanor M. [Henry Ford Hospital, Detroit, Michigan (United States); Grills, Inga S. [Beaumont Health System, Royal Oak, Michigan (United States); Boike, Thomas [McLaren Northern Michigan, Petoskey, Michigan (United States); Feng, Mary; Moran, Jean M.; Hayman, James; Pierce, Lori J. [University of Michigan, Ann Arbor, Michigan (United States)

    2014-12-01

    Purpose: Given evidence from randomized trials that have established the non-inferiority of more convenient and less costly courses of hypofractionated radiotherapy to the whole breast in selected breast cancer patients who receive lumpectomy, we sought to investigate the use of hypofractionated radiation therapy and factors associated with its use in a consortium of radiation oncology practices in Michigan. We sought to determine the extent to which variation in use occurs at the physician or practice level versus the extent to which use reflects individualization based on potentially relevant patient characteristics (such as habitus, age, chemotherapy receipt, or laterality). Methods and Materials: We evaluated associations between receipt of hypofractionated radiation therapy and various patient, provider, and practice characteristics in a multilevel model. Results: Of 1477 patients who received lumpectomy and whole-breast radiation therapy and were registered by the Michigan Radiation Oncology Quality Consortium (MROQC) from October 2011 to December 2013, 913 had T1-2, N0 breast cancer. Of these 913, 283 (31%) received hypofractionated radiation therapy. Among the 13 practices, hypofractionated radiation therapy use ranged from 2% to 80%. On multilevel analysis, 51% of the variation in the rate of hypofractionation was attributable to the practice level, 21% to the provider level, and 28% to the patient level. On multivariable analysis, hypofractionation was more likely in patients who were older (odds ratio [OR] 2.16 for age ≥50 years, P=.007), less likely in those with larger body habitus (OR 0.52 if separation between tangent entry and exit ≥25 cm, P=.002), and more likely without chemotherapy receipt (OR 3.82, P<.001). Hypofractionation use was not higher in the last 6 months analyzed: 79 of 252 (31%) from June 2013 to December 2013 and 204 of 661 (31%) from October 2011 to May 2013 (P=.9). Conclusions: Hypofractionated regimens of whole

  14. The Pattern of Use of Hypofractionated Radiation Therapy for Early-Stage Breast Cancer in New South Wales, Australia, 2008 to 2012

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    Delaney, Geoff P., E-mail: Geoff.delaney@swsahs.nsw.gov.au [Liverpool Cancer Therapy Centre, Liverpool, New South Wales (Australia); Collaboration for Cancer Outcomes Research and Evaluation, University of New South Wales, Sydney (Australia); Ingham Health and Medical Research Institute, Sydney (Australia); New South Wales Cancer Institute (Australia); Gandhidasan, Senthilkumar [Peter MacCallum Cancer Centre, Melbourne (Australia); Walton, Richard; Terlich, Frances; Baker, Deborah; Currow, David [New South Wales Cancer Institute (Australia)

    2016-10-01

    Purpose: Increasing phase 3 evidence has been published about the safety and efficacy of hypofractionated radiation therapy, in comparison with standard fractionation, in early-stage, node-negative breast cancer. However, uptake of hypofractionation has not been universal. The aim of this study was to investigate the hypofractionation regimen variations in practice across public radiation oncology facilities in New South Wales (NSW). Methods and Materials: Patients with early breast cancer registered in the NSW Clinical Cancer Registry who received radiation therapy for early-stage breast cancer in a publicly funded radiation therapy department between 2008 and 2012 were identified. Data extracted and analyzed included dose and fractionation type, patient age at first fraction, address (for geocoding), year of diagnosis, year of treatment, laterality, and department of treatment. A logistic regression model was used to identify factors associated with fractionation type. Results: Of the 5880 patients fulfilling the study criteria, 3209 patients (55%) received standard fractionation and 2671 patients (45%) received hypofractionation. Overall, the use of hypofractionation increased from 37% in 2008 to 48% in 2012 (range, 7%-94% across departments). Treatment facility and the radiation oncologist prescribing the treatment were the strongest independent predictors of hypofractionation. Weaker associations were also found for age, tumor site laterality, year of treatment, and distance to facility. Conclusions: Hypofractionated regimens of whole breast radiation therapy have been variably administered in the adjuvant setting in NSW despite the publication of long-term trial results and consensus guidelines. Some factors that predict the use of hypofractionation are not based on guideline recommendations, including lower rates of left-sided treatment and increasing distance from a treatment facility.

  15. Sucralfate gel as a radioprotector against radiation induced dermatitis in a hypo-fractionated schedule: a non-randomized study.

    Science.gov (United States)

    Kouloulias, V; Asimakopoulos, C; Tolia, M; Filippou, G; Platoni, K; Dilvoi, M; Beli, I; Georgakopoulos, J; Patatoukas, G; Kelekis, N

    2013-04-01

    External beam radiotherapy with high doses provokes many acute skin reactions, such as erythema and moist desquamation. Many topical preparations are used in radiation oncology departments in the skin care. Sucralfate humid gel, a colloidal physical form of the anti-ulcer drug sucralfate, promotes epithelial regeneration and activates cell proliferation. Based on this knowledge, we performed a non-randomized clinical trial to evaluate the efficacy of topical sucralfate gel in 30 breast cancer patients receiving postoperative accelerated hypofractionated photon beam therapy. The comparison was performed with 30 patients as historical controls. The acute reaction of the skin was significantly lower in the group receiving the sucralfate gel (p<0.05, Mann Whitney test), while 90% of the patients had no evidence of radiation induced skin toxicity. There was no sucralfate gel related toxicity reported by any patient in this study. More patients in a randomized way are needed for more definite results.

  16. Hypofractionation vs Conventional Radiation Therapy for Newly Diagnosed Diffuse Intrinsic Pontine Glioma: A Matched-Cohort Analysis

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    Janssens, Geert O., E-mail: g.janssens@rther.umcn.nl [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Jansen, Marc H. [Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam (Netherlands); Lauwers, Selmer J. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Nowak, Peter J. [Department of Radiation Oncology, Erasmus Medical Centre, Rotterdam (Netherlands); Oldenburger, Foppe R. [Department of Radiation Oncology, Academic Medical Centre, Amsterdam (Netherlands); Bouffet, Eric [Department of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto (Canada); Saran, Frank [Department of Pediatric Oncology, The Royal Marsden NHS Foundation Trust, Sutton (United Kingdom); Kamphuis-van Ulzen, Karin [Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Lindert, Erik J. van [Department of Neurosurgery, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Schieving, Jolanda H. [Department of Neurology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Boterberg, Tom [Department of Radiation Oncology, Ghent University Hospital, Ghent (Belgium); Kaspers, Gertjan J. [Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam (Netherlands); Span, Paul N.; Kaanders, Johannes H. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Gidding, Corrie E. [Department of Pediatric Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Hargrave, Darren [Department of Oncology, Great Ormond Street Hospital, London (United Kingdom)

    2013-02-01

    Purpose: Despite conventional radiation therapy, 54 Gy in single doses of 1.8 Gy (54/1.8 Gy) over 6 weeks, most children with diffuse intrinsic pontine glioma (DIPG) will die within 1 year after diagnosis. To reduce patient burden, we investigated the role of hypofractionation radiation therapy given over 3 to 4 weeks. A 1:1 matched-cohort analysis with conventional radiation therapy was performed to assess response and survival. Methods and Materials: Twenty-seven children, aged 3 to 14, were treated according to 1 of 2 hypofractionation regimens over 3 to 4 weeks (39/3 Gy, n=16 or 44.8/2.8 Gy, n=11). All patients had symptoms for {<=}3 months, {>=}2 signs of the neurologic triad (cranial nerve deficit, ataxia, long tract signs), and characteristic features of DIPG on magnetic resonance imaging. Twenty-seven patients fulfilling the same diagnostic criteria and receiving at least 50/1.8 to 2.0 Gy were eligible for the matched-cohort analysis. Results: With hypofractionation radiation therapy, the overall survival at 6, 9, and 12 months was 74%, 44%, and 22%, respectively. Progression-free survival at 3, 6, and 9 months was 77%, 43%, and 12%, respectively. Temporary discontinuation of steroids was observed in 21 of 27 (78%) patients. No significant difference in median overall survival (9.0 vs 9.4 months; P=.84) and time to progression (5.0 vs 7.6 months; P=.24) was observed between hypofractionation vs conventional radiation therapy, respectively. Conclusions: For patients with newly diagnosed DIPG, a hypofractionation regimen, given over 3 to 4 weeks, offers equal overall survival with less treatment burden compared with a conventional regimen of 6 weeks.

  17. Hypofractionated Whole-Breast Radiation Therapy: Does Breast Size Matter?

    International Nuclear Information System (INIS)

    Hannan, Raquibul; Thompson, Reid F.; Chen Yu; Bernstein, Karen; Kabarriti, Rafi; Skinner, William; Chen, Chin C.; Landau, Evan; Miller, Ekeni; Spierer, Marnee; Hong, Linda; Kalnicki, Shalom

    2012-01-01

    Purpose: To evaluate the effects of breast size on dose-volume histogram parameters and clinical toxicity in whole-breast hypofractionated radiation therapy using intensity modulated radiation therapy (IMRT). Materials and Methods: In this retrospective study, all patients undergoing breast-conserving therapy between 2005 and 2009 were screened, and qualifying consecutive patients were included in 1 of 2 cohorts: large-breasted patients (chest wall separation >25 cm or planning target volume [PTV] >1500 cm 3 ) (n=97) and small-breasted patients (chest wall separation 3 ) (n=32). All patients were treated prone or supine with hypofractionated IMRT to the whole breast (42.4 Gy in 16 fractions) followed by a boost dose (9.6 Gy in 4 fractions). Dosimetric and clinical toxicity data were collected and analyzed using the R statistical package (version 2.12). Results: The mean PTV V95 (percentage of volume receiving >= 95% of prescribed dose) was 90.18% and the mean V105 percentage of volume receiving >= 105% of prescribed dose was 3.55% with no dose greater than 107%. PTV dose was independent of breast size, whereas heart dose and maximum point dose to skin correlated with increasing breast size. Lung dose was markedly decreased in prone compared with supine treatments. Radiation Therapy Oncology Group grade 0, 1, and 2 skin toxicities were noted acutely in 6%, 69%, and 25% of patients, respectively, and at later follow-up (>3 months) in 43%, 57%, and 0% of patients, respectively. Large breast size contributed to increased acute grade 2 toxicity (28% vs 12%, P=.008). Conclusions: Adequate PTV coverage with acceptable hot spots and excellent sparing of organs at risk was achieved by use of IMRT regardless of treatment position and breast size. Although increasing breast size leads to increased heart dose and maximum skin dose, heart dose remained within our institutional constraints and the incidence of overall skin toxicity was comparable to that reported in the

  18. Adoption of Hypofractionated Radiation Therapy for Breast Cancer After Publication of Randomized Trials

    International Nuclear Information System (INIS)

    Jagsi, Reshma; Falchook, Aaron D.; Hendrix, Laura H.; Curry, Heather; Chen, Ronald C.

    2014-01-01

    Purpose: Large randomized trials have established the noninferiority of shorter courses of “hypofractionated” radiation therapy (RT) to the whole breast compared to conventional courses using smaller daily doses in the adjuvant treatment of selected breast cancer patients undergoing lumpectomy. Hypofractionation is more convenient and less costly. Therefore, we sought to determine uptake of hypofractionated breast RT over time. Methods and Materials: In the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database, we identified 16,096 women with node-negative breast cancer and 4269 with ductal carcinoma in situ (DCIS) who received lumpectomy followed by more than 12 fractions of RT between 2004 and 2010. Based on Medicare claims, we determined the number of RT treatments given and grouped patients into those receiving hypofractionation (13-24) or those receiving conventional fractionation (≥25). We also determined RT technique (intensity modulated RT or not) using Medicare claims. We evaluated patterns and correlates of hypofractionation receipt using bivariate and multivariable analyses. Results: Hypofractionation use was similar in patients with DCIS and those with invasive disease. Overall, the use of hypofractionation increased from 3.8% in 2006 to 5.4% in 2007, to 9.4% in 2008, and to 13.6% in 2009 and 2010. Multivariable analysis showed increased use of hypofractionation in recent years and in patients with older age, smaller tumors, increased comorbidity, higher regional education, and Western SEER regions. However, even in patients over the age of 80, the hypofractionation rate in 2009 to 2010 was only 25%. Use of intensity modulated RT (IMRT) also increased over time (from 9.4% in 2004 to 22.7% in 2009-2010) and did not vary significantly between patients receiving hypofractionation and those receiving traditional fractionation. Conclusions: Hypofractionation use increased among low-risk older US breast cancer patients with

  19. Adoption of Hypofractionated Radiation Therapy for Breast Cancer After Publication of Randomized Trials

    Energy Technology Data Exchange (ETDEWEB)

    Jagsi, Reshma, E-mail: rjagsi@med.umich.edu [Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan (United States); Falchook, Aaron D.; Hendrix, Laura H. [Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Curry, Heather [Radiation Oncology, Eviti, Inc, Philadelphia, Pennsylvania (United States); Chen, Ronald C. [Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States)

    2014-12-01

    Purpose: Large randomized trials have established the noninferiority of shorter courses of “hypofractionated” radiation therapy (RT) to the whole breast compared to conventional courses using smaller daily doses in the adjuvant treatment of selected breast cancer patients undergoing lumpectomy. Hypofractionation is more convenient and less costly. Therefore, we sought to determine uptake of hypofractionated breast RT over time. Methods and Materials: In the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database, we identified 16,096 women with node-negative breast cancer and 4269 with ductal carcinoma in situ (DCIS) who received lumpectomy followed by more than 12 fractions of RT between 2004 and 2010. Based on Medicare claims, we determined the number of RT treatments given and grouped patients into those receiving hypofractionation (13-24) or those receiving conventional fractionation (≥25). We also determined RT technique (intensity modulated RT or not) using Medicare claims. We evaluated patterns and correlates of hypofractionation receipt using bivariate and multivariable analyses. Results: Hypofractionation use was similar in patients with DCIS and those with invasive disease. Overall, the use of hypofractionation increased from 3.8% in 2006 to 5.4% in 2007, to 9.4% in 2008, and to 13.6% in 2009 and 2010. Multivariable analysis showed increased use of hypofractionation in recent years and in patients with older age, smaller tumors, increased comorbidity, higher regional education, and Western SEER regions. However, even in patients over the age of 80, the hypofractionation rate in 2009 to 2010 was only 25%. Use of intensity modulated RT (IMRT) also increased over time (from 9.4% in 2004 to 22.7% in 2009-2010) and did not vary significantly between patients receiving hypofractionation and those receiving traditional fractionation. Conclusions: Hypofractionation use increased among low-risk older US breast cancer patients with

  20. Geographic Disparity in the Use of Hypofractionated Radiation Therapy Among Elderly Women Undergoing Breast Conservation for Invasive Breast Cancer

    International Nuclear Information System (INIS)

    Gillespie, Erin F.; Matsuno, Rayna K.; Xu, Beibei; Triplett, Daniel P.; Hwang, Lindsay; Boero, Isabel J.; Einck, John P.; Yashar, Catheryn; Murphy, James D.

    2016-01-01

    Purpose: To evaluate geographic heterogeneity in the delivery of hypofractionated radiation therapy (RT) for breast cancer among Medicare beneficiaries across the United States. Methods and Materials: We identified 190,193 patients from the Centers for Medicare and Medicaid Services Chronic Conditions Warehouse. The study included patients aged >65 years diagnosed with invasive breast cancer treated with breast conservation surgery followed by radiation diagnosed between 2000 and 2012. We analyzed data by hospital referral region based on patient residency ZIP code. The proportion of women who received hypofractionated RT within each region was analyzed over the study period. Multivariable logistic regression models identified predictors of hypofractionated RT. Results: Over the entire study period we found substantial geographic heterogeneity in the use of hypofractionated RT. The proportion of women receiving hypofractionated breast RT in individual hospital referral regions varied from 0% to 61%. We found no correlation between the use of hypofractionated RT and urban/rural setting or general geographic region. The proportion of hypofractionated RT increased in regions with higher density of radiation oncologists, as well as lower total Medicare reimbursements. Conclusions: This study demonstrates substantial geographic heterogeneity in the use of hypofractionated RT among elderly women with invasive breast cancer treated with lumpectomy in the United States. This heterogeneity persists despite clinical data from multiple randomized trials proving efficacy and safety compared with standard fractionation, and highlights possible inefficiency in health care delivery.

  1. Geographic Disparity in the Use of Hypofractionated Radiation Therapy Among Elderly Women Undergoing Breast Conservation for Invasive Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gillespie, Erin F.; Matsuno, Rayna K.; Xu, Beibei; Triplett, Daniel P.; Hwang, Lindsay; Boero, Isabel J.; Einck, John P.; Yashar, Catheryn; Murphy, James D., E-mail: j2murphy@ucsd.edu

    2016-10-01

    Purpose: To evaluate geographic heterogeneity in the delivery of hypofractionated radiation therapy (RT) for breast cancer among Medicare beneficiaries across the United States. Methods and Materials: We identified 190,193 patients from the Centers for Medicare and Medicaid Services Chronic Conditions Warehouse. The study included patients aged >65 years diagnosed with invasive breast cancer treated with breast conservation surgery followed by radiation diagnosed between 2000 and 2012. We analyzed data by hospital referral region based on patient residency ZIP code. The proportion of women who received hypofractionated RT within each region was analyzed over the study period. Multivariable logistic regression models identified predictors of hypofractionated RT. Results: Over the entire study period we found substantial geographic heterogeneity in the use of hypofractionated RT. The proportion of women receiving hypofractionated breast RT in individual hospital referral regions varied from 0% to 61%. We found no correlation between the use of hypofractionated RT and urban/rural setting or general geographic region. The proportion of hypofractionated RT increased in regions with higher density of radiation oncologists, as well as lower total Medicare reimbursements. Conclusions: This study demonstrates substantial geographic heterogeneity in the use of hypofractionated RT among elderly women with invasive breast cancer treated with lumpectomy in the United States. This heterogeneity persists despite clinical data from multiple randomized trials proving efficacy and safety compared with standard fractionation, and highlights possible inefficiency in health care delivery.

  2. Hypofractionated Breast Radiation: Shorter Scheme, Lower Toxicity.

    Science.gov (United States)

    Linares, Isabel; Tovar, María Isabel; Zurita, Mercedes; Guerrero, Rosario; Expósito, Manuela; Del Moral, Rosario

    2016-08-01

    We analyzed the toxicity and cosmetic outcomes for patients who had undergone 3-dimensional conformal radiotherapy with a hypofractionated schedule and identified the risk factors associated with such a schedule. A total of 143 patients were treated for breast cancer (stage 0-III) with a hypofractionated radiation schedule after breast-conserving surgery from 2006 to 2011. Most patients received 42.4 Gy in 16 daily fractions, 2.65 Gy per fraction to the whole breast plus an additional simultaneous integrated or sequential boost to the tumor bed. The median follow-up period was 36 months. Mild acute skin toxicity was observed in 62%; 7% of the patients developed moderate skin toxicity, but no grade 4 toxicity was observed. The prevalence of fibrosis within the boost area was 5%, but no grade ≥ 2 was observed. The prevalence of fibrosis of any grade was greater in the nonboost (23%) than in the boost area. Of all the patients, 91% had good or excellent cosmetic outcomes. From the multivariate analysis, the incidence of epithelitis correlated with the patient's treated volume (P = .044). The incidence of acute toxicity correlated with the boost type to the tumor bed and the total treatment dose (P = .012 and P = .002, respectively). Also, a poor to fair cosmetic outcome was significantly associated statistically with the surgery type (P = .05), boost type (P = .004), and total dose (P = .001). Delivering whole-breast irradiation with a hypofractionated schedule of 42.4 Gy plus a simultaneous integrated boost to the tumor bed appears to be a safe and effective technique, with good cosmetic results and lower toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Hypofractionated Whole-Breast Radiation Therapy: Does Breast Size Matter?

    Energy Technology Data Exchange (ETDEWEB)

    Hannan, Raquibul, E-mail: Raquibul.Hannan@gmail.com [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Thompson, Reid F.; Chen Yu; Bernstein, Karen; Kabarriti, Rafi; Skinner, William [Department of Radiation Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York (United States); Chen, Chin C. [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States); Landau, Evan; Miller, Ekeni; Spierer, Marnee; Hong, Linda; Kalnicki, Shalom [Department of Radiation Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York (United States)

    2012-11-15

    Purpose: To evaluate the effects of breast size on dose-volume histogram parameters and clinical toxicity in whole-breast hypofractionated radiation therapy using intensity modulated radiation therapy (IMRT). Materials and Methods: In this retrospective study, all patients undergoing breast-conserving therapy between 2005 and 2009 were screened, and qualifying consecutive patients were included in 1 of 2 cohorts: large-breasted patients (chest wall separation >25 cm or planning target volume [PTV] >1500 cm{sub 3}) (n=97) and small-breasted patients (chest wall separation <25 cm and PTV <1500 cm{sub 3}) (n=32). All patients were treated prone or supine with hypofractionated IMRT to the whole breast (42.4 Gy in 16 fractions) followed by a boost dose (9.6 Gy in 4 fractions). Dosimetric and clinical toxicity data were collected and analyzed using the R statistical package (version 2.12). Results: The mean PTV V95 (percentage of volume receiving >= 95% of prescribed dose) was 90.18% and the mean V105 percentage of volume receiving >= 105% of prescribed dose was 3.55% with no dose greater than 107%. PTV dose was independent of breast size, whereas heart dose and maximum point dose to skin correlated with increasing breast size. Lung dose was markedly decreased in prone compared with supine treatments. Radiation Therapy Oncology Group grade 0, 1, and 2 skin toxicities were noted acutely in 6%, 69%, and 25% of patients, respectively, and at later follow-up (>3 months) in 43%, 57%, and 0% of patients, respectively. Large breast size contributed to increased acute grade 2 toxicity (28% vs 12%, P=.008). Conclusions: Adequate PTV coverage with acceptable hot spots and excellent sparing of organs at risk was achieved by use of IMRT regardless of treatment position and breast size. Although increasing breast size leads to increased heart dose and maximum skin dose, heart dose remained within our institutional constraints and the incidence of overall skin toxicity was comparable

  4. Hypofractionated stereotactic radiation therapy for recurrent glioblastoma: single institutional experience

    International Nuclear Information System (INIS)

    Ciammella, Patrizia; Podgornii, Ala; Galeandro, Maria; D’Abbiero, Nunziata; Pisanello, Anna; Botti, Andrea; Cagni, Elisabetta; Iori, Mauro; Iotti, Cinzia

    2013-01-01

    Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Tumor control and survival have improved with the use of radiotherapy (RT) plus concomitant and adjuvant chemotherapy, but the prognosis remain poor. In most cases the recurrence occurs within 7–9 months after primary treatment. Currently, many approaches are available for the salvage treatment of patients with recurrent GBM, including resection, re-irradiation or systemic agents, but no standard of care exists. We analysed a cohort of patients with recurrent GBM treated with frame-less hypofractionated stereotactic radiation therapy with a total dose of 25 Gy in 5 fractions. Of 91 consecutive patients with newly diagnosed GBM treated between 2007 and 2012 with conventional adjuvant chemo-radiation therapy, 15 underwent salvage RT at recurrence. The median time interval between primary RT and salvage RT was 10.8 months (range, 6–54 months). Overall, patients undergoing salvage RT showed a longer survival, with a median survival of 33 vs. 9.9 months (p= 0.00149). Median overall survival (OS) from salvage RT was 9.5 months. No patients demonstrated clinically significant acute morbidity, and all patients were able to complete the prescribed radiation therapy without interruption. Our results suggest that hypofractionated stereotactic radiation therapy is effective and safe in recurrent GBM. However, until prospective randomized trials will confirm these results, the decision for salvage treatment should remain individual and based on a multidisciplinary evaluation of each patient

  5. On the importance of prompt oxygen changes for hypofractionated radiation treatments

    International Nuclear Information System (INIS)

    Kissick, Michael; Campos, David; Van der Kogel, Albert; Kimple, Randall

    2013-01-01

    This discussion is motivated by observations of prompt oxygen changes occurring prior to a significant number of cancer cells dying (permanently stopping their metabolic activity) from therapeutic agents like large doses of ionizing radiation. Such changes must be from changes in the vasculature that supplies the tissue or from the metabolic changes in the tissue itself. An adapted linear–quadratic treatment is used to estimate the cell survival variation magnitudes from repair and reoxygenation from a two-fraction treatment in which the second fraction would happen prior to significant cell death from the first fraction, in the large fraction limit. It is clear the effects of oxygen changes are likely to be the most significant factor for hypofractionation because of large radiation doses. It is a larger effect than repair. Optimal dose timing should be determined by the peak oxygen timing. A call is made to prioritize near real time measurements of oxygen dynamics in tumors undergoing hypofractionated treatments in order to make these treatments adaptable and patient-specific. (note)

  6. Accelerated hypofractionated three-dimensional conformal radiation therapy in the treatment of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Yu Jinming; Zheng Aiqing; Yu Yonghua; Wang Xuetao; Yuan Shuanghu; Han Dali; Li Kunhai

    2005-01-01

    Objective: To evaluate the effect and complication of non-small-cell lung cancer (NSCLC) treated with accelerated hypofractionated three dimensional conforms] radiation therapy (3DCRT). Methods: There were squamous carcinoma 21, adenocarcinoma 7, squamous-adenocarcinoma 4 and other cancer 3. There were 17 stage I and 18 stage II. Thirty-five patients of NSCLC were treated with a dose of 30-48 Gy in 6 or 8 Gy per fraction, 3 times a week. The outcome of these patients Was analyzed. Results: The overall 1-, 2- and 3- Year survival rate was 78.2%, 46.9% and 36.3%, respectively. The 1- and 2-year recurrence-free survival rate was 64.6 % and 39.7 %, respectively. The acute radiation pneumonitis and late lung fibrosis rates were high. Univariate analysis showed that Vm was a significant predictor of acute radiation pneumonitis. Conclusion: Compared with accelerated hypofractionated irradiation, the routine conventional fractionated radiation therapy may be preferred for more patients of NSCLC. (authors)

  7. Role of the Technical Aspects of Hypofractionated Radiation Therapy Treatment of Prostate Cancer: A Review

    Energy Technology Data Exchange (ETDEWEB)

    Clemente, Stefania, E-mail: clemente_stefania@libero.it [Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico della Basilicata Rionero in Vulture, Potenza (Italy); Nigro, Roberta [Azienda Sanitaria Locale Rieti, Roma (Italy); Oliviero, Caterina [Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico della Basilicata Rionero in Vulture, Potenza (Italy); Marchioni, Chiara [Azienda Sanitaria Locale Rieti, Roma (Italy); Esposito, Marco [Azienda Sanitaria, Firenze (Italy); Giglioli, Francesca Romana [Azienda Ospedaliera Città della Salute e della Scienza di Torino, Torino (Italy); Mancosu, Pietro [Humanitas Clinical and Research Hospital, Rozzano, Milano (Italy); Marino, Carmelo [Humanitas Centro Catanese di Oncologia, Catania (Italy); Russo, Serenella [Azienda Sanitaria, Firenze (Italy); Stasi, Michele [Azienda Ospedaliera Ordine Mauriziano di Torino, Torino (Italy); Strigari, Lidia [Istituto Nazionale Tumori Regina Elena, Roma (Italy); Veronese, Ivan [Universita' degli Studi di Milano, Milano (Italy); Landoni, Valeria [Istituto Nazionale Tumori Regina Elena, Roma (Italy)

    2015-01-01

    The increasing use of moderate (<35 fractions) and extreme (<5 fractions) hypofractionated radiation therapy in prostate cancer is yielding favorable results, both in terms of maintained biochemical response and toxicity. Several hypofractionation (HF) schemes for the treatment of prostate cancer are available, although there is considerable variability in the techniques used to manage intra-/interfraction motion and deliver radiation doses. We performed a review of the published studies on HF regimens as a topic of interest for the Stereotactic Ablative Radiotherapy working group, which is part of the Italian Association of Medical Physics. Aspects of organ motion management (imaging for contouring, target volume definition, and rectum/bladder preparation) and treatment delivery (prostate localization, image guided radiation therapy strategy and frequency) were evaluated and categorized to assess outcome relative to disease control and toxicity. Despite the heterogeneity of the data, some interesting trends that emerged from the review might be useful in identifying an optimum HF strategy.

  8. Hypofractionated electron-beam radiation therapy for keloids. Retrospective study of 568 cases with 834 lesions

    International Nuclear Information System (INIS)

    Shen Jie; Lian Xin; Sun Yuliang

    2015-01-01

    We aimed to analyze the outcomes of hypofractionated high-energy electron beam radiotherapy for the treatment of keloids. From February 1998 to January 2012, 568 patients with a total of 834 keloids underwent radiotherapy: 826 lesions with postoperative radiotherapy, and 36 with skin-grafting. Lesion size was >5 cm in 335 keloids. An electron-beam of 6 or 7 MeV was used, with a total dose of 18 Gy (two fractions with a 1-week interval) covering the lesion with a 1-cm margin. The time between surgery and radiotherapy was 24–48 h. Skin-grafted patients underwent radiotherapy 10–15 days after the operation. The median follow-up was 40 months (range: 12–160 months). The local control rate was 88.25% (736/834). The relapse rate was 9.59% (80/834), and the time to relapse was 6–28 months (median: 12 months). Univariate analyses showed that gender, age, keloid size, keloid site, skin grafting, and operation-to-irradiation interval influenced the local control rate. Multivariate analysis showed that the relapse rate was correlated with gender (P = 0.048), age (P < 0.01), operation-to-irradiation interval (P < 0.01), keloid site (P < 0.01), surgical method (P = 0.04) and keloid size (P < 0.02). Adverse effects were observed in 9.83% (82/834). No radiation-induced cancers were observed. Hypofractionated high-energy electron beam radiotherapy for keloids yielded excellent outcomes, especially in cases without skin grafting. Early postoperative radiotherapy with limited hypofractionation could be a good choice for keloid treatment. (author)

  9. Hypofractionated radiation induces a decrease in cell proliferation but no histological damage to organotypic multicellular spheroids of human glioblastomas

    International Nuclear Information System (INIS)

    Kaaijk, P.; Academic Medical Center, Amsterdam; Troost, D.; Leenstra, S.; Bosch, D.A.; Sminia, P.; Hulshof, M.C.C.M..; Kracht, A.H.W. van der

    1997-01-01

    The aim of this study was to examine the effect of radiation on glioblastoma, using an organotypic multicellular spheroid (OMS) model. Most glioblastoma cell lines are, in contrast to glioblastomas in vivo, relatively radiosensitive. This limits the value of using cell lines for studying the radiation effect of glioblastomas. The advantage of OMS is maintenance of the characteristics of the original tumour, which is lost in conventional cell cultures. OMS prepared from four glioblastomas were treated with hypofractionated radiation with a radiobiologically equivalent dose to standard radiation treatment for glioblastomas patients. After treatment, the histology as well as the cell proliferation of the OMS was examined. After radiation, a significant decrease in cell proliferation was found, although no histological damage to the OMS was observed. The modest effects of radiation on the OMS are in agreement with the limited therapeutic value of radiotherapy for glioblastoma patients. Therefore, OMS seems to be a good alternative for cell lines to study the radiobiological effect on glioblastomas. (author)

  10. Hypofractionated radiation induces a decrease in cell proliferation but no histological damage to organotypic multicellular spheroids of human glioblastomas

    Energy Technology Data Exchange (ETDEWEB)

    Kaaijk, P [Academic Medical Center, Amsterdam (Netherlands). Dept. of (Neuro) Pathology; [Academic Medical Center, Amsterdam (Netherlands). Dept. of Neurosurgery; Troost, D [Academic Medical Center, Amsterdam (Netherlands). Dept. of (Neuro) Pathology; Leenstra, S; Bosch, D A [Academic Medical Center, Amsterdam (Netherlands). Dept. of Neurosurgery; Sminia, P; Hulshof, M C.C.M.; Kracht, A.H.W. van der [Academic Medical Center, Amsterdam (Netherlands). Dept. of (Experimental) Radiotherapy

    1997-04-01

    The aim of this study was to examine the effect of radiation on glioblastoma, using an organotypic multicellular spheroid (OMS) model. Most glioblastoma cell lines are, in contrast to glioblastomas in vivo, relatively radiosensitive. This limits the value of using cell lines for studying the radiation effect of glioblastomas. The advantage of OMS is maintenance of the characteristics of the original tumour, which is lost in conventional cell cultures. OMS prepared from four glioblastomas were treated with hypofractionated radiation with a radiobiologically equivalent dose to standard radiation treatment for glioblastomas patients. After treatment, the histology as well as the cell proliferation of the OMS was examined. After radiation, a significant decrease in cell proliferation was found, although no histological damage to the OMS was observed. The modest effects of radiation on the OMS are in agreement with the limited therapeutic value of radiotherapy for glioblastoma patients. Therefore, OMS seems to be a good alternative for cell lines to study the radiobiological effect on glioblastomas. (author).

  11. Radiation-induced myelopathy in long-term surviving metastatic spinal cord compression patients after hypofractionated radiotherapy: a clinical and magnetic resonance imaging analysis

    International Nuclear Information System (INIS)

    Maranzano, Ernesto; Bellavita, Rita; Floridi, Piero; Celani, Grazia; Righetti, Enrico; Lupattelli, Marco; Panizza, Bianca Moira; Frattegiani, Alessandro; Pelliccioli, Gian Piero; Latini, Paolo

    2001-01-01

    Background and purpose: Hypofractionated radiotherapy is often administered in metastatic spinal cord compression (MSCC), but no studies have been published on the incidence of radiation-induced myelopathy (RIM) in long-term surviving patients. Our report addresses this topic. Patients and methods: Of 465 consecutive MSCC patients submitted to radiotherapy between 1988 and 1997, 13 live patients (seven females, six males, median age 69 years, median follow-up 69 months) surviving for 2 years or more were retrospectively reviewed to evaluate RIM. All patients underwent radiotherapy. Eight patients underwent a short-course regimen of 8 Gy, with 7 days rest, and then another 8 Gy. Five patients underwent a split-course regimen of 5 Gy x3, 4 days rest, and then 3 Gy x5. Only one patient also underwent laminectomy. Full neurological examination and magnetic resonance imaging (MRI) were performed. Results: Of 12 patients submitted to radiotherapy alone, 11 were ambulant (eight without support and three with support) with good bladder function. In nine of these 11 patients, MRI was negative; in one case MRI evidenced an in-field relapse 30 months after the end of radiotherapy, and in the other, two new MSCC foci outside the irradiated spine. In the remaining patient RIM was suspected at 18 months after radiotherapy when the patient became paraplegic and cystoplegic, and magnetic resonance images evidenced an ischemic injury in the irradiated area. The only patient treated with surgery plus postoperative radiotherapy worsened and remained paraparetic. Magnetic resonance images showed cord atrophy at the surgical level, explained as an ischemic necrosis due to surgery injury. Conclusions: On the grounds of our data regarding RIM in long-term surviving MSCC patients, we believe that a hypofractionated radiotherapy regimen can be used for the majority of patients. For a minority of patients, more protracted radiation regimens could be considered

  12. Hypofractionated regional nodal irradiation for breast cancer: Examining the data and potential for future studies

    International Nuclear Information System (INIS)

    Badiyan, Shahed N.; Shah, Chirag; Arthur, Douglas; Khan, Atif J.; Freedman, Gary; Poppe, Matthew M.; Vicini, Frank A.

    2014-01-01

    Limited data are available examining the role of hypofractionated radiation schedules in the management of women requiring regional nodal irradiation (RNI). The purpose of this review is to examine the available literature for the efficacy (where available) and toxicity of hypofractionated radiation schedules in breast cancer with RNI limited to the axilla and supraclavicular regions. Multiple randomized and prospective studies have documented the safety and efficacy of hypofractionated schedules delivering whole breast irradiation (WBI) alone. Subsets from these randomized trials and smaller prospective/single-institution studies have documented the feasibility of hypofractionated RNI but the limited numbers prevent definitive conclusions and limited efficacy data are available. With regard to possible toxicity affecting organs at risk with RNI, key structures include the breast, skin, heart, lungs, axilla (lymphedema), and brachial plexus. Based on data from several randomized trials, hypofractionated radiation is not associated with significant changes in breast toxicity/cosmesis or cardiac toxicity; the addition of hypofractionated RNI would not be expected to change the rates of breast or cardiac toxicity. While RNI has been shown to increase rates of pulmonary toxicity, hypofractionated RNI has not been associated with more frequent pulmonary complications than standard RNI. Moving forward, future studies will have to evaluate for increased lung toxicity. With regard to lymphedema, data from randomized hypofractionated WBI trials failed to demonstrate an increase in lymphedema and smaller studies utilizing hypofractionated RNI have failed to as well. Data from head and neck cancer as well as hypofractionated breast radiation with RNI have failed to demonstrate an increase in brachial plexopathy with the exception of older trials that used much larger dose per fraction (>4 Gy/fraction) schedules. At this time, published data support the feasibility of

  13. Hypofractionated stereotactic irradiation. Basic and clinical researches

    International Nuclear Information System (INIS)

    Shibamoto, Yuta; Miyakawa, Akifumi; Iwata, Hiromitsu; Otsuka, Shinya; Ogino, Hiroyuki; Ayakawa, Shiho

    2011-01-01

    Hypofractionated stereotactic radiotherapy (SRT) has a number of biological advantages over single-session radiosurgery. An apparent trend is seen in the clinic towards shift from the latter to the former; however, there is no adequate model to convert single doses to hypofractionated doses. The linear-quadratic model overestimates the effect of single-fraction radiation. This should be kept in mind in evaluating the doses of stereotactic irradiation. ''Biological effective dose'' should not be used in radiosurgery and hypofractionated SRT. Clinically, we have used 3- to 10-fraction SRT for acoustic neuroma and benign skull base tumors using cyberknife and tomotherapy. Preliminary results are encouraging. (author)

  14. [Hypofractionated radiation therapy for the treatment of malignant melanoma and squamous cell carcinoma in dogs and cats].

    Science.gov (United States)

    Kinzel, Sylvia; Hein, Sven; Stopinski, Thaddeus; Koch, Johannes; Buecker, Arno; Treusacher, Hans-Peter; Schmachtenberg, Axel; Jansen, Thomas; Eble, Michael; Küpper, Wernen

    2003-01-01

    This study describes the experience with hypofractionated radiation therapy of squamous cell carcinoma and melanoma in dogs and cats. A total dose of 32-48 Gray (Gy) was delivered once a week in 8 Gy fractions. 34 animals in which a complete surgical excision was impossible were treated. There was no tumor detectable macroscopically in 14 patients at the beginning of radiation therapy. In 20 animals the median volume of the tumor was 9.9 cm3. The median survival times and the local tumor control of squamous cell carcinoma of the oral and nasal cavities and of the body are comparable to results which were reached with a Monday-Wednesday-Friday scheme. For the treatment of Melanoma the hypofractionated radiation therapy is first choice. There are no significant side effects. Late side effects did not occur. 88% of the owners are satisfied with this kind of treatment and would choose it again.

  15. Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, Karen E., E-mail: khoffman1@mdanderson.org; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

    2014-04-01

    Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

  16. Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

    International Nuclear Information System (INIS)

    Hoffman, Karen E.; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

    2014-01-01

    Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

  17. Prostate hypofractionated radiation therapy with injection of hyaluronic acid: acute toxicities in a phase 2 study.

    Science.gov (United States)

    Chapet, Olivier; Decullier, Evelyne; Bin, Sylvie; Faix, Antoine; Ruffion, Alain; Jalade, Patrice; Fenoglietto, Pascal; Udrescu, Corina; Enachescu, Ciprian; Azria, David

    2015-03-15

    Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    International Nuclear Information System (INIS)

    Chapet, Olivier; Decullier, Evelyne; Bin, Sylvie; Faix, Antoine; Ruffion, Alain; Jalade, Patrice; Fenoglietto, Pascal; Udrescu, Corina; Enachescu, Ciprian; Azria, David

    2015-01-01

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity

  19. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); EMR3738, Université Lyon 1, Lyon (France); Decullier, Evelyne; Bin, Sylvie [Pole Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon (France); Université Lyon 1, Lyon (France); EA SIS, Université de Lyon, Lyon (France); Faix, Antoine [Department of Urology, Clinique Beausoleil, Montpellier (France); Ruffion, Alain [Université Lyon 1, Lyon (France); Department of Urology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Jalade, Patrice [Department of Medical Physics, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Fenoglietto, Pascal [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France); Udrescu, Corina; Enachescu, Ciprian [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Azria, David [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France)

    2015-03-15

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

  20. Hypofractionated radiotherapy for invasive bladder cancer

    International Nuclear Information System (INIS)

    Scholten, Astrid N.; Leer, Jan-Willem H.; Collins, C. David; Wondergem, Jan; Hermans, Jo; Timothy, Adrian

    1997-01-01

    Background and purpose: The policy of the Radiotherapy Department of St. Thomas' Hospital in London for patients with invasive bladder cancer, used to be treatment with hypofractionated radiotherapy. The advantages of this fractionation scheme included reduction of the number of treatment sessions and better use of limited resources. Our results after hypofractionation were compared to series with more conventional radiotherapy. Material and methods: Between 1975 and 1985, 123 patients with a T2-T3 transitional cell carcinoma of the bladder were treated by a radical course of hypofractionated radiotherapy. Local control, survival and morbidity rates were analysed retrospectively. Results: The actuarial local control rates at 5 and 10 years were 31 and 29%, respectively. The actuarial cancer-specific 5- and 10-year survival rates were 48 and 39%, respectively. Acute side effects were observed in 87% of patients. The actuarial overall and severe late complication rates at 5 years were 33 and 9%, respectively. The local control, survival and early side effect rates we found, were in the same range as those reported in literature. Late radiation side effects however, were more common after hypofractionated radiotherapy compared to conventional radiotherapy schedules. Conclusions: We conclude that the potential advantage of a reduced number of treatment sessions may be lost in the long term, because of the higher incidence of late morbidity after hypofractionated radiotherapy. Hypofractionation however, remains a valuable technique for palliation and deserves further investigation for radical treatment where access to equipment is difficult or resources are limited

  1. Accelerated hypofractionated radiation therapy compared to conventionally fractionated radiation therapy for the treatment of inoperable non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Amini Arya

    2012-03-01

    Full Text Available Abstract Background While conventionally fractionated radiation therapy alone is an acceptable option for poor prognostic patients with unresectable stage III NSCLC, we hypothesized that accelerated hypofractionated radiotherapy will have similar efficacy without increasing toxicity. Methods This is a retrospective analysis of 300 patients diagnosed with stage III NSCLC treated between 1993 and 2009. Patients included in the study were medically or surgically inoperable, were free of metastatic disease at initial workup and did not receive concurrent chemotherapy. Patients were categorized into three groups. Group 1 received 45 Gy in 15 fractions over 3 weeks (Accelerated Radiotherapy (ACRT while group 2 received 60-63 Gy (Standard Radiation Therapy 1 (STRT1 and group 3 received > 63 Gy (Standard Radiation Therapy (STRT2. Results There were 119 (39.7% patients in the ACRT group, 90 (30.0% in STRT1 and 91 (30.3% in STRT2. More patients in the ACRT group had KPS ≤ 60 (p 5% (p = 0.002, and had stage 3B disease (p Conclusions Despite the limitations of a retrospective analysis, our experience of accelerated hypofractionated radiation therapy with 45 Gy in 15 fractions appears to be an acceptable treatment option for poor performance status patients with stage III inoperable tumors. Such a treatment regimen (or higher doses in 15 fractions should be prospectively evaluated using modern radiation technologies with the addition of sequential high dose chemotherapy in stage III NSCLC.

  2. Radiobiology of hypofractionated stereotactic radiotherapy: what are the optimal fractionation schedules?

    International Nuclear Information System (INIS)

    Shibamoto, Yuta; Miyakawa, Akifumi; Otsuka, Shinya; Iwata, Hiromitsu

    2016-01-01

    In hypofractionated stereotactic radiotherapy (SRT), high doses per fraction are usually used and the dose delivery pattern is different from that of conventional radiation. The daily dose is usually given intermittently over a longer time compared with conventional radiotherapy. During prolonged radiation delivery, sublethal damage repair takes place, leading to the decreased effect of radiation. In in vivo tumors, however, this decrease in effect may be counterbalanced by rapid reoxygenation. Another issue related to hypofractionated SRT is the mathematical model for dose evaluation and conversion. The linear–quadratic (LQ) model and biologically effective dose (BED) have been suggested to be incorrect when used for hypofractionation. The LQ model overestimates the effect of high fractional doses of radiation. BED is particularly incorrect when used for tumor responses in vivo, since it does not take reoxygenation into account. Correction of the errors, estimated at 5–20%, associated with the use of BED is necessary when it is used for SRT. High fractional doses have been reported to exhibit effects against tumor vasculature and enhance host immunity, leading to increased antitumor effects. This may be an interesting topic that should be further investigated. Radioresistance of hypoxic tumor cells is more problematic in hypofractionated SRT, so trials of hypoxia-targeted agents are encouraged in the future. In this review, the radiobiological characteristics of hypofractionated SRT are summarized, and based on the considerations, we would like to recommend 60 Gy in eight fractions delivered three times a week for lung tumors larger than 2 cm in diameter

  3. A Dosimetric Comparison between Conventional Fractionated and Hypofractionated Image-guided Radiation Therapies for Localized Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Ming Li

    2016-01-01

    Conclusions: To deliver the hypofractionated radiotherapy in prostate cancer, VMAT significantly increased PTV D95% dose and decreased the dose of radiation delivered to adjacent normal tissues comparing to 7-field, step-and-shoot IMRT. Daily online image-guidance and better management of bladder and rectum could make a more precise treatment delivery.

  4. Evaluation of image-guided radiation therapy (IGRT) technologies and their impact on the outcomes of hypofractionated prostate cancer treatments: A radiobiologic analysis

    International Nuclear Information System (INIS)

    Song, William Y.; Schaly, Bryan; Bauman, Glenn; Battista, Jerry J.; Van Dyk, Jake

    2006-01-01

    Purpose: To quantify the mitigation of geometric uncertainties achieved with the application of various patient setup techniques during the delivery of hypofractionated prostate cancer treatments, using tumor control probability (TCP) and normal tissue complication probability. Methods and Materials: Five prostate cancer patients with ∼16 treatment CT studies, taken during the course of their radiation therapy (77 total), were analyzed. All patients were planned twice with an 18 MV six-field conformal technique, with 10- and 5-mm margin sizes, with various hypofractionation schedules (5 to 35 fractions). Subsequently, four clinically relevant patient setup techniques (laser guided and image guided) were simulated to deliver such schedules. Results: As hypothesized, the impact of geometric uncertainties on clinical outcomes increased with more hypofractionated schedules. However, the absolute gain in TCP due to hypofractionation (up to 21.8% increase) was significantly higher compared with the losses due to geometric uncertainties (up to 8.6% decrease). Conclusions: The results of this study suggest that, although the impact of geometric uncertainties on the treatment outcomes increases as the number of fractions decrease, the reduction in TCP due to the uncertainties does not significantly offset the expected theoretical gain in TCP by hypofractionation

  5. Dose-volume histogram analysis for risk factors of radiation-induced rib fracture after hypofractionated proton beam therapy for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kanemoto, Ayae

    2013-01-01

    Background: Radiation-induced rib fracture has been reported as a late complication after external radiotherapy to the chest. The purpose of this study was to clarify the characteristics and risk factors of rib fracture after hypofractionated proton beam therapy (PBT). Material and methods: The retrospective study comprised 67 patients with hepatocellular carcinoma who were treated using PBT of 66 Cobalt-Gray-equivalents [Gy (RBE)] in 10 fractions. We analyzed the patients' characteristics and determined dose-volume histograms (DVHs) for the irradiated ribs, and then estimated relationships between risk of fracture and several dose-volume parameters. An irradiated rib was defined to be any rib included in the area irradiated by PBT as determined by treatment-planning computed tomography. Results. Among the 67 patients, a total of 310 ribs were identified as irradiated ribs. Twenty-seven (8.7%) of the irradiated ribs developed fractures in 11 patients (16.4%). No significant relationships were seen between incidence of fracture and characteristics of patients, including sex, age, tumor size, tumor site, and follow-up period (p ≥ 0.05). The results of receiver operating characteristic curve analysis using DVH parameters demonstrated that the largest area under the curve (AUC) was observed for the volume of rib receiving a biologically effective dose of more than 60 Gy 3 (RBE) (V60) [The equivalent dose in 2 Gy fractions (EQD2); 36 Gy 3 ] and the AUCs of V30 to V120 (EQD2; 18-72 Gy 3 ) and D max to D 1 0 cm 3 were similar to that of V60. No significant relationships were seen for DVH parameters and intervals from PBT to incidence of fracture. Conclusion. DVH parameters are useful in predicting late adverse events of rib irradiation. This study identified that V60 was a most statistically significant parameter, and V30 to V120 and D max to D 1 0 cm 3 were also significant and clinically useful for estimating the risk of rib fracture after hypofractionated PBT

  6. Dose-volume histogram analysis for risk factors of radiation-induced rib fracture after hypofractionated proton beam therapy for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kanemoto, Ayae [Proton Medical Research Center and Dept. of Radiation Oncology, Univ. of Tsukuba, Ibaraki (Japan)], e-mail: ayaek@pmrc.tsukuba.ac.jp [and others

    2013-04-15

    Background: Radiation-induced rib fracture has been reported as a late complication after external radiotherapy to the chest. The purpose of this study was to clarify the characteristics and risk factors of rib fracture after hypofractionated proton beam therapy (PBT). Material and methods: The retrospective study comprised 67 patients with hepatocellular carcinoma who were treated using PBT of 66 Cobalt-Gray-equivalents [Gy (RBE)] in 10 fractions. We analyzed the patients' characteristics and determined dose-volume histograms (DVHs) for the irradiated ribs, and then estimated relationships between risk of fracture and several dose-volume parameters. An irradiated rib was defined to be any rib included in the area irradiated by PBT as determined by treatment-planning computed tomography. Results. Among the 67 patients, a total of 310 ribs were identified as irradiated ribs. Twenty-seven (8.7%) of the irradiated ribs developed fractures in 11 patients (16.4%). No significant relationships were seen between incidence of fracture and characteristics of patients, including sex, age, tumor size, tumor site, and follow-up period (p {>=} 0.05). The results of receiver operating characteristic curve analysis using DVH parameters demonstrated that the largest area under the curve (AUC) was observed for the volume of rib receiving a biologically effective dose of more than 60 Gy{sub 3} (RBE) (V60) [The equivalent dose in 2 Gy fractions (EQD2); 36 Gy{sub 3}] and the AUCs of V30 to V120 (EQD2; 18-72 Gy{sub 3}) and D{sub max} to D{sub 1}0{sub cm}{sup 3} were similar to that of V60. No significant relationships were seen for DVH parameters and intervals from PBT to incidence of fracture. Conclusion. DVH parameters are useful in predicting late adverse events of rib irradiation. This study identified that V60 was a most statistically significant parameter, and V30 to V120 and D{sub max} to D{sub 1}0{sub cm}{sup 3} were also significant and clinically useful for estimating

  7. Mild Lung Restriction in Breast Cancer Patients After Hypofractionated and Conventional Radiation Therapy: A 3-Year Follow-Up

    International Nuclear Information System (INIS)

    Verbanck, Sylvia; Hanon, Shane; Schuermans, Daniel; Van Parijs, Hilde; Vinh-Hung, Vincent; Miedema, Geertje; Verellen, Dirk; Storme, Guy; Fontaine, Christel; Lamote, Jan; De Ridder, Mark; Vincken, Walter

    2016-01-01

    Purpose: To assess the effect of radiation therapy on lung function over the course of 3 years. Methods and Materials: Evolution of restrictive and obstructive lung function parameters was investigated in 108 breast cancer participants in a randomized, controlled trial comparing conventional radiation therapy (CR) and hypofractionated tomotherapy (TT) (age at inclusion ranging 32-81 years). Spirometry, plethysmography, and hemoglobin-corrected diffusing capacity were assessed at baseline and after 3 months and 1, 2, and 3 years. Natural aging was accounted for by considering all lung function parameters in terms of percent predicted values using the most recent reference values for women aged up to 80 years. Results: In the patients with negligible history of respiratory disease or smoking (n=77), the greatest rate of functional decline was observed during the initial 3 months, this acute decrease being more marked in the CR versus the TT arm. During the remainder of the 3-year follow-up period, values (in terms of percent predicted) were maintained (diffusing capacity) or continued to decline at a slower rate (forced vital capacity). However, the average decline of the restrictive lung function parameters over a 3-year period did not exceed 9% predicted in either the TT or the CR arm. Obstructive lung function parameters remained unaffected throughout. Including also the 31 patients with a history of respiratory disease or more than 10 pack-years showed a very similar restrictive pattern. Conclusions: In women with breast cancer, both conventional radiation therapy and hypofractionated tomotherapy induce small but consistent restrictive lung patterns over the course of a 3-year period, irrespective of baseline respiratory status or smoking history. The fastest rate of lung function decline generally occurred in the first 3 months.

  8. Mild Lung Restriction in Breast Cancer Patients After Hypofractionated and Conventional Radiation Therapy: A 3-Year Follow-Up

    Energy Technology Data Exchange (ETDEWEB)

    Verbanck, Sylvia, E-mail: sylvia.verbanck@uzbrussel.be [Respiratory Division, University Hospital UZ Brussel, Brussels (Belgium); Hanon, Shane; Schuermans, Daniel [Respiratory Division, University Hospital UZ Brussel, Brussels (Belgium); Van Parijs, Hilde; Vinh-Hung, Vincent; Miedema, Geertje; Verellen, Dirk; Storme, Guy [Department of Radiotherapy, University Hospital UZ Brussel, Brussels (Belgium); Fontaine, Christel; Lamote, Jan [Department of Senology and Oncologic Surgery, University Hospital UZ Brussel, Brussels (Belgium); De Ridder, Mark [Department of Radiotherapy, University Hospital UZ Brussel, Brussels (Belgium); Vincken, Walter [Respiratory Division, University Hospital UZ Brussel, Brussels (Belgium)

    2016-07-01

    Purpose: To assess the effect of radiation therapy on lung function over the course of 3 years. Methods and Materials: Evolution of restrictive and obstructive lung function parameters was investigated in 108 breast cancer participants in a randomized, controlled trial comparing conventional radiation therapy (CR) and hypofractionated tomotherapy (TT) (age at inclusion ranging 32-81 years). Spirometry, plethysmography, and hemoglobin-corrected diffusing capacity were assessed at baseline and after 3 months and 1, 2, and 3 years. Natural aging was accounted for by considering all lung function parameters in terms of percent predicted values using the most recent reference values for women aged up to 80 years. Results: In the patients with negligible history of respiratory disease or smoking (n=77), the greatest rate of functional decline was observed during the initial 3 months, this acute decrease being more marked in the CR versus the TT arm. During the remainder of the 3-year follow-up period, values (in terms of percent predicted) were maintained (diffusing capacity) or continued to decline at a slower rate (forced vital capacity). However, the average decline of the restrictive lung function parameters over a 3-year period did not exceed 9% predicted in either the TT or the CR arm. Obstructive lung function parameters remained unaffected throughout. Including also the 31 patients with a history of respiratory disease or more than 10 pack-years showed a very similar restrictive pattern. Conclusions: In women with breast cancer, both conventional radiation therapy and hypofractionated tomotherapy induce small but consistent restrictive lung patterns over the course of a 3-year period, irrespective of baseline respiratory status or smoking history. The fastest rate of lung function decline generally occurred in the first 3 months.

  9. Extreme Hypofractionated Image-Guided Radiotherapy for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Carlo Greco

    2013-09-01

    Full Text Available An emerging body of data suggests that hypofractionated radiation schedules, where a higher dose per fraction is delivered in a smaller number of sessions, may be superior to conventional fractionation schemes in terms of both tumour control and toxicity profile in the management of adenocarcinoma of the prostate. However, the optimal hypofractionation scheme is still the subject of scientific debate. Modern computer-driven technology enables the safe implementation of extreme hypo fractionation (often referred to as stereotactic body radiation therapy [SBRT]. Several studies are currently being conducted to clarify the yet unresolved issues regarding treatment techniques and fractionation regimens. Recently, the American Society for Radiation Oncology (ASTRO issued a model policy indicating that data supporting the use of SBRT for prostate cancer have matured to a point where SBRT could be considered an appropriate alternative for select patients with low-to-intermediate risk disease. The present article reviews some of the currently available data and examines the impact of tracking technology to mitigate intra-fraction target motion, thus, potentially further improving the clinical outcomes of extreme hypofractionated radiation therapy in appropriately selected prostate cancer patients. The Champalimaud Centre for the Unknown (CCU’s currently ongoing Phase I feasibility study is described; it delivers 45 Gy in five fractions using prostate fixation via a rectal balloon, and urethral sparing via catheter placement with on-line intra-fractional motion tracking through beacon transponder technology.

  10. [Practice evolution of hypofractionation in breast radiation therapy and medical impact].

    Science.gov (United States)

    Dupin, C; Vilotte, F; Lagarde, P; Petit, A; Breton-Callu, C

    2016-06-01

    Whole breast irradiation after conservative surgery is the standard treatment for invasive breast cancer. Randomized studies indicate that hypofractionation can be equivalent for selected patients. This study focuses on fractionation practice evolution in a single centre, and analyses the economic impact of practice modification. All prescriptions for invasive breast cancer between January 2010 and June 2014 were analyzed. Female patients 60 years or older, pN0 were considered for the economic study. Patients included in clinical trials or patient with high-grade tumours were excluded from the hypofractionation practice study, because physician could not choose fractionation. We used data from the Medical public health system to calculate cost per fraction and transportation cost. Two thousand thirty one patients were treated; 399 were eligible for the economic study (20%) and 282 for the practice study (14%). Treatment with 25 fractions decreased from 90% to 16% in the first half of 2014. Meanwhile, treatment with 15 or 16 fractions increased from 6% in 2010 to 68% in the first half of 2014. Hypofractionated treatment proportion was 100% with 42.5Gy in 16 fractions in 2010 and 100% 40Gy in 15 fractions in 2014, according to long-term follow-up publication of START trials. Treatment with five fractions remained stable around 7% (4 to 16%), reserved for patients over 80 years (PPractice change led to an increase of hypofractionation in recent years. Hypofractionation may be currently prescribed and may concern 20% of patients. This practice evolution is beneficial for patients and the public health system. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  11. Hypofractionated Versus Standard Radiation Therapy With or Without Temozolomide for Older Glioblastoma Patients

    International Nuclear Information System (INIS)

    Arvold, Nils D.; Tanguturi, Shyam K.; Aizer, Ayal A.; Wen, Patrick Y.; Reardon, David A.; Lee, Eudocia Q.; Nayak, Lakshmi; Christianson, Laura W.; Horvath, Margaret C.; Dunn, Ian F.; Golby, Alexandra J.; Johnson, Mark D.; Claus, Elizabeth B.; Chiocca, E. Antonio; Ligon, Keith L.; Alexander, Brian M.

    2015-01-01

    Purpose: Older patients with newly diagnosed glioblastoma have poor outcomes, and optimal treatment is controversial. Hypofractionated radiation therapy (HRT) is frequently used but has not been compared to patients receiving standard fractionated radiation therapy (SRT) and temozolomide (TMZ). Methods and Materials: We conducted a retrospective analysis of patients ≥65 years of age who received radiation for the treatment of newly diagnosed glioblastoma from 1994 to 2013. The distribution of clinical covariates across various radiation regimens was analyzed for possible selection bias. Survival was calculated using the Kaplan-Meier method. Comparison of hypofractionated radiation (typically, 40 Gy/15 fractions) versus standard fractionation (typically, 60 Gy/30 fractions) in the setting of temozolomide was conducted using Cox regression and propensity score analysis. Results: Patients received SRT + TMZ (n=57), SRT (n=35), HRT + TMZ (n=34), or HRT (n=9). Patients receiving HRT were significantly older (median: 79 vs 69 years of age; P<.001) and had worse baseline performance status (P<.001) than those receiving SRT. On multivariate analysis, older age (adjusted hazard ratio [AHR]: 1.06; 95% confidence interval [CI]: 1.01-1.10, P=.01), lower Karnofsky performance status (AHR: 1.02; 95% CI: 1.01-1.03; P=.01), multifocal disease (AHR: 2.11; 95% CI: 1.23-3.61, P=.007), and radiation alone (vs SRT + TMZ; SRT: AHR: 1.72; 95% CI: 1.06-2.79; P=.03; HRT: AHR: 3.92; 95% CI: 1.44-10.60, P=.007) were associated with decreased overall survival. After propensity score adjustment, patients receiving HRT with TMZ had similar overall survival compared with those receiving SRT with TMZ (AHR: 1.10, 95% CI: 0.50-2.4, P=.82). Conclusions: With no randomized data demonstrating equivalence between HRT and SRT in the setting of TMZ for glioblastoma, significant selection bias exists in the implementation of HRT. Controlling for this bias, we observed similar overall

  12. Hypofractionated Versus Standard Radiation Therapy With or Without Temozolomide for Older Glioblastoma Patients

    Energy Technology Data Exchange (ETDEWEB)

    Arvold, Nils D. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States); Tanguturi, Shyam K. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Aizer, Ayal A. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States); Wen, Patrick Y.; Reardon, David A.; Lee, Eudocia Q.; Nayak, Lakshmi [Center for Neuro-Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States); Christianson, Laura W.; Horvath, Margaret C. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States); Dunn, Ian F.; Golby, Alexandra J.; Johnson, Mark D. [Department of Neurosurgery, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States); Claus, Elizabeth B. [Department of Neurosurgery, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States); School of Public Health, Yale University, New Haven, Connecticut (United States); Chiocca, E. Antonio [Department of Neurosurgery, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States); Ligon, Keith L. [Department of Pathology, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States); Alexander, Brian M., E-mail: bmalexander@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States)

    2015-06-01

    Purpose: Older patients with newly diagnosed glioblastoma have poor outcomes, and optimal treatment is controversial. Hypofractionated radiation therapy (HRT) is frequently used but has not been compared to patients receiving standard fractionated radiation therapy (SRT) and temozolomide (TMZ). Methods and Materials: We conducted a retrospective analysis of patients ≥65 years of age who received radiation for the treatment of newly diagnosed glioblastoma from 1994 to 2013. The distribution of clinical covariates across various radiation regimens was analyzed for possible selection bias. Survival was calculated using the Kaplan-Meier method. Comparison of hypofractionated radiation (typically, 40 Gy/15 fractions) versus standard fractionation (typically, 60 Gy/30 fractions) in the setting of temozolomide was conducted using Cox regression and propensity score analysis. Results: Patients received SRT + TMZ (n=57), SRT (n=35), HRT + TMZ (n=34), or HRT (n=9). Patients receiving HRT were significantly older (median: 79 vs 69 years of age; P<.001) and had worse baseline performance status (P<.001) than those receiving SRT. On multivariate analysis, older age (adjusted hazard ratio [AHR]: 1.06; 95% confidence interval [CI]: 1.01-1.10, P=.01), lower Karnofsky performance status (AHR: 1.02; 95% CI: 1.01-1.03; P=.01), multifocal disease (AHR: 2.11; 95% CI: 1.23-3.61, P=.007), and radiation alone (vs SRT + TMZ; SRT: AHR: 1.72; 95% CI: 1.06-2.79; P=.03; HRT: AHR: 3.92; 95% CI: 1.44-10.60, P=.007) were associated with decreased overall survival. After propensity score adjustment, patients receiving HRT with TMZ had similar overall survival compared with those receiving SRT with TMZ (AHR: 1.10, 95% CI: 0.50-2.4, P=.82). Conclusions: With no randomized data demonstrating equivalence between HRT and SRT in the setting of TMZ for glioblastoma, significant selection bias exists in the implementation of HRT. Controlling for this bias, we observed similar overall

  13. The hypo-fractionated radiotherapy in the treatment of the prostate cancer: Radiate less to treat more

    International Nuclear Information System (INIS)

    Boissier, R.; Gross, E.

    2012-01-01

    The principle of the hypo-fractionation in radiotherapy is to deliver a higher dose by session and to reduce the duration of treatment. In the particular case of the cancer of prostate, a hypo-fractionated protocol allows to deliver an equivalent radiobiological dose identical even higher than a standard plan of irradiation. The hypo-fractionation is presented as a solution to improve the access to the care (fewer processing times by patient, more patients treated by machine) while increasing the quality of the care: better carcinological control, less radiotoxicity. The objective of this article is to make a clarification on the hypo-fractionated radiotherapy in first intention in the treatment of the localized prostate cancer. We count three studies on large cohorts, comparing standard plans to 1.8 2 Gy/session and hypo-fractionated plans (2.5 3 Gy/session). The inferior carcinological results of the two first comparative studies with regard to the study of phase I/II of the Cleveland clinic were owed to a sub-dosage of hypo-fractionated plans. The administered equivalent biological doses were lower than the at present recommended total doses and lower than the theoretical doses, calculated on the bases of an erroneous evaluation of the radio-sensibility of the prostate cancer. In the comparative study of Arcangeli, the rate of survival without biological recurrence in 4 years (82%) was significantly to the advantage of the hypo-fractionated group, while reducing the duration of treatment of 3 weeks. Four comparative studies reported acute/late toxicity, gastrointestinal (GI)/genito-urinary acceptable (GU) even lower with a hypo-fractionated plan. The hypo-fractionation is potentially the future of the radiotherapy in the treatment of the localized prostate cancer thanks to the technological innovation, but for all that does not constitute at present a standard. (authors)

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

    Energy Technology Data Exchange (ETDEWEB)

    Fonteyne, Valerie, E-mail: valerie.fonteyne@uzgent.be [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Soete, Guy [Department of Radiotherapy, Universitair Ziekenhuis Brussels, Jette (Belgium); Arcangeli, Stefano [Department of Radiotherapy, Regina Elena National Cancer Institute, Rome (Italy); De Neve, Wilfried [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Rappe, Bernard [Department of Urology, Algemeen Stedelijk Ziekenhuis, Aalst (Belgium); Storme, Guy [Department of Radiotherapy, Universitair Ziekenhuis Brussels, Jette (Belgium); Strigari, Lidia [Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome (Italy); Arcangeli, Giorgio [Department of Radiotherapy, Regina Elena National Cancer Institute, Rome (Italy); De Meerleer, Gert [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium)

    2012-11-15

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

  15. Hypofractionated stereotactic radiotherapy for malignant tumors of the lung

    Directory of Open Access Journals (Sweden)

    О. Ю. Аникеева

    2015-10-01

    Full Text Available Hypofractionated stereotactic radiotherapy was used for 26 patients at medically inoperable stage I of non-small cell lung cancer with dose escalation of 48-54 Gy prescribed at 90 or 95% isodose level in 3-4 fractions. Nine-months local control and cancer-specific survival were 82.0 and 66.8% respectively, with minimal toxicity. For metastatic lung tumors local control was obtained in 92% cases. Hypofractionated stereotactic radiation therapy (SBRT is safe and feasible for the treatment of inoperable primary lung cancer and single lung metastasis.

  16. Stereotactic Radiosurgery and Hypofractionated Radiotherapy for Glioblastoma.

    Science.gov (United States)

    Shah, Jennifer L; Li, Gordon; Shaffer, Jenny L; Azoulay, Melissa I; Gibbs, Iris C; Nagpal, Seema; Soltys, Scott G

    2018-01-01

    Glioblastoma is the most common primary brain tumor in adults. Standard therapy depends on patient age and performance status but principally involves surgical resection followed by a 6-wk course of radiation therapy given concurrently with temozolomide chemotherapy. Despite such treatment, prognosis remains poor, with a median survival of 16 mo. Challenges in achieving local control, maintaining quality of life, and limiting toxicity plague treatment strategies for this disease. Radiotherapy dose intensification through hypofractionation and stereotactic radiosurgery is a promising strategy that has been explored to meet these challenges. We review the use of hypofractionated radiotherapy and stereotactic radiosurgery for patients with newly diagnosed and recurrent glioblastoma. Copyright © 2017 by the Congress of Neurological Surgeons.

  17. Five-Year Follow-Up of Concomitant Accelerated Hypofractionated Radiation in Advanced Squamous Cell Carcinoma of the Buccal Mucosa: A Retrospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Hassan Iqbal

    2015-01-01

    Full Text Available In resource limited settings, induction chemotherapy with Gemcitabine and Cisplatinum and concurrent hypofractionated chemoradiation for locally advanced carcinoma of buccal mucosa (BMSCC are a cost effective option but remain under reported. The objective of this study was to report long term survival outcome after concurrent hypofractionated radiotherapy in locally advanced BMSCC. Between February 2005 and 2009, 63 patients received treatment. Induction chemotherapy (IC regimen consisted of two drugs: Gemcitabine and Cisplatin. All patients received 55 Gy of radiation in 20 fractions with concurrent single agent Cisplatin (75 mg/m2. Five-year overall survival (OS, disease-free survival (DFS, and progression-free survival (PFS were determined. Based on AJCC staging, 7 (11% patients were stage III, 31 (49% stage IV a, and 25 (40% stage IVb at presentation. After IC, 8 (18% patients had complete radiological response, 33 (73% had partial response, and 4 (9% had stable disease. After concurrent hypofractionated chemoradiation, thirty-nine (62% patients were complete responders and 24 (38% had stable disease. With a minimum follow-up of 60 months, 5-year OS, DFS, and PFS were 30%, 49%, and 30%, respectively. In locally advanced buccal mucosa squamous cell carcinoma, concurrent hypofractionated chemoradiation results in acceptable survival and regimen related toxicity.

  18. Hypofractionated IMRT of the Prostate Bed After Radical Prostatectomy: Acute Toxicity in the PRIAMOS-1 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Katayama, Sonja, E-mail: sonja.katayama@med.uni-heidelberg.de [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany); Striecker, Thorbjoern; Kessel, Kerstin [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany); Sterzing, Florian [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany); Department of Radiation Oncology, German Cancer Research Center, Im Neuenheimer Feld, Heidelberg (Germany); Habl, Gregor [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany); Edler, Lutz [Department of Biostatistics, German Cancer Research Center, Im Neuenheimer Feld, Heidelberg (Germany); Debus, Juergen [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany); Department of Radiation Oncology, German Cancer Research Center, Im Neuenheimer Feld, Heidelberg (Germany); Herfarth, Klaus [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany)

    2014-11-15

    Purpose: Hypofractionated radiation therapy as primary treatment for prostate cancer is currently being investigated in large phase 3 trials. However, there are few data on postoperative hypofractionation. The Radiation therapy for the Prostate Bed With or Without the Pelvic Lymph Nodes (PRIAMOS 1) trial was initiated as a prospective phase 2 trial to assess treatment safety and toxicity of a hypofractionated intensity modulated radiation therapy (IMRT) of the prostate bed. Methods and Materials: From February to September 2012, 40 patients with indications for adjuvant or salvage radiation therapy were enrolled. One patient dropped out before treatment. Patients received 54 Gy in 18 fractions to the prostate bed with IMRT and daily image guidance. Gastrointestinal (GI) and genitourinary (GU) toxicities (according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) were recorded weekly during treatment and 10 weeks after radiation therapy. Results: Overall acute toxicity was favorable, with no recorded adverse events grade ≥3. Acute GI toxicity rates were 56.4% (grade 1) and 17.9% (grade 2). Acute GU toxicity was recorded in 35.9% of patients (maximum grade 1). Urinary stress incontinence was not influenced by radiation therapy. The incidence of grade 1 urinary urge incontinence increased from 2.6% before to 23.1% 10 weeks after therapy, but grade 2 urge incontinence remained unchanged. Conclusions: Postoperative hypofractionated IMRT of the prostate bed is tolerated well, with no severe acute side effects.

  19. Retrospective study of canine nasal tumor treated with hypofractionated radiotherapy

    International Nuclear Information System (INIS)

    Maruo, Takuya; Shida, Takuo; Fukuyama, Yasuhiro; Hosaka, Soshi; Noda, Masashi; Ito, Tetsuro; Sugiyama, Hiroki; Ishikawa, Takeshi; Madarame, Hiroo

    2011-01-01

    The object of this study was to evaluate hypofractionated multiportal field and two-portion (rostral and caudal portions divided by the eyelid) radiation therapy for canine nasal tumors. Sixty-three dogs underwent multiportal hypofractionated radiation therapy. The radiation field was divided into rostral and caudal portions by the eyelid. Treatments were performed four times for 57 dogs. The median irradiation dose/fraction was 8 Gy (range, 5-10 Gy); the median total dose was 32 Gy (10-40 Gy). Improvement of clinical symptoms was achieved in 53 (84.1%) of 63 cases. Median survival time was 197 days (range, 2-1,080 days). Median survival times with and without destruction of the cribriform plate before radiotherapy were 163 and 219 days, respectively. There was no significant difference between them. No other factors were related to survival according to a univariate analysis. All radiation side effects, except one, were grade I according to the VRTOG classification. It was not necessary to treat any dogs for skin side effects. One dog (1.6%) developed an oronasal fistula 1 year after completion of radiation therapy. This radiation protocol may be useful in reducing radiation side effects in dogs with cribriform plate destruction. (author)

  20. Adoption of Hypofractionated Whole-Breast Irradiation for Early-Stage Breast Cancer: A National Cancer Data Base Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Elyn H. [Yale School of Medicine, Yale School of Medicine, New Haven, Connecticut (United States); Mougalian, Sarah S. [Yale School of Medicine, Yale School of Medicine, New Haven, Connecticut (United States); Department of Medical Oncology, Yale School of Medicine, New Haven, Connecticut (United States); Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale, New Haven, Connecticut (United States); Soulos, Pamela R. [Yale School of Medicine, Yale School of Medicine, New Haven, Connecticut (United States); Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale, New Haven, Connecticut (United States); Rutter, Charles E.; Evans, Suzanne B. [Yale School of Medicine, Yale School of Medicine, New Haven, Connecticut (United States); Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale, New Haven, Connecticut (United States); Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Haffty, Bruce G. [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, New Jersey (United States); Gross, Cary P. [Yale School of Medicine, Yale School of Medicine, New Haven, Connecticut (United States); Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, New Jersey (United States); Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut (United States); Yu, James B., E-mail: james.b.yu@yale.edu [Yale School of Medicine, Yale School of Medicine, New Haven, Connecticut (United States); Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale, New Haven, Connecticut (United States); Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States)

    2014-12-01

    Purpose: To evaluate the relationship of patient, hospital, and cancer characteristics with the adoption of hypofractionation in a national sample of patients diagnosed with early-stage breast cancer. Methods and Materials: We performed a retrospective study of breast cancer patients in the National Cancer Data Base from 2004-2011 who were treated with radiation therapy and met eligibility criteria for hypofractionation. We used logistic regression to identify factors associated with receipt of hypofractionation (vs conventional fractionation). Results: We identified 13,271 women (11.7%) and 99,996 women (88.3%) with early-stage breast cancer who were treated with hypofractionation and conventional fractionation, respectively. The use of hypofractionation increased significantly, with 5.4% of patients receiving it in 2004 compared with 22.8% in 2011 (P<.001 for trend). Patients living ≥50 miles from the cancer reporting facility had increased odds of receiving hypofractionation (odds ratio 1.57 [95% confidence interval 1.44-1.72], P<.001). Adoption of hypofractionation was associated with treatment at an academic center (P<.001) and living in an area with high median income (P<.001). Hypofractionation was less likely to be used in patients with high-risk disease, such as increased tumor size (P<.001) or poorly differentiated histologic grade (P<.001). Conclusions: The use of hypofractionation is rising and is associated with increased travel distance and treatment at an academic center. Further adoption of hypofractionation may be tempered by both clinical and nonclinical concerns.

  1. Adoption of Hypofractionated Whole-Breast Irradiation for Early-Stage Breast Cancer: A National Cancer Data Base Analysis

    International Nuclear Information System (INIS)

    Wang, Elyn H.; Mougalian, Sarah S.; Soulos, Pamela R.; Rutter, Charles E.; Evans, Suzanne B.; Haffty, Bruce G.; Gross, Cary P.; Yu, James B.

    2014-01-01

    Purpose: To evaluate the relationship of patient, hospital, and cancer characteristics with the adoption of hypofractionation in a national sample of patients diagnosed with early-stage breast cancer. Methods and Materials: We performed a retrospective study of breast cancer patients in the National Cancer Data Base from 2004-2011 who were treated with radiation therapy and met eligibility criteria for hypofractionation. We used logistic regression to identify factors associated with receipt of hypofractionation (vs conventional fractionation). Results: We identified 13,271 women (11.7%) and 99,996 women (88.3%) with early-stage breast cancer who were treated with hypofractionation and conventional fractionation, respectively. The use of hypofractionation increased significantly, with 5.4% of patients receiving it in 2004 compared with 22.8% in 2011 (P<.001 for trend). Patients living ≥50 miles from the cancer reporting facility had increased odds of receiving hypofractionation (odds ratio 1.57 [95% confidence interval 1.44-1.72], P<.001). Adoption of hypofractionation was associated with treatment at an academic center (P<.001) and living in an area with high median income (P<.001). Hypofractionation was less likely to be used in patients with high-risk disease, such as increased tumor size (P<.001) or poorly differentiated histologic grade (P<.001). Conclusions: The use of hypofractionation is rising and is associated with increased travel distance and treatment at an academic center. Further adoption of hypofractionation may be tempered by both clinical and nonclinical concerns

  2. Hypofractionated Intensity Modulated Radiation Therapy in Combined Modality Treatment for Bladder Preservation in Elderly Patients With Invasive Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Turgeon, Guy-Anne [Department of Oncology, Division of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Souhami, Luis, E-mail: luis.souhami@muhc.mcgill.ca [Department of Oncology, Division of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Cury, Fabio L.; Faria, Sergio L.; Duclos, Marie [Department of Oncology, Division of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Sturgeon, Jeremy [Department of Medical Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Kassouf, Wassim [Department of Urology, McGill University Health Centre, Montreal, Quebec (Canada)

    2014-02-01

    Purpose/Objective(s): To review our experience with bladder-preserving trimodality treatment (TMT) using hypofractionated intensity modulated radiation therapy (IMRT) for the treatment of elderly patients with muscle-invasive bladder cancer. Methods and Materials: Retrospective study of elderly patients treated with TMT using hypofractionated IMRT (50 Gy in 20 fractions) with concomitant weekly radiosensitizing chemotherapy. Eligibility criteria were as follows: age ≥70 years, a proven diagnosis of muscle-invasive transitional cell bladder carcinoma, stage T2-T3N0M0 disease, and receipt of TMT with curative intent. Response rate was assessed by cystoscopic evaluation and bladder biopsy. Results: 24 patients with a median age of 79 years were eligible. A complete response was confirmed in 83% of the patients. Of the remaining patients, 1 of them underwent salvage cystectomy, and no disease was found in the bladder on histopathologic assessment. After a median follow-up time of 28 months, of the patients with a complete response, 2 patients had muscle-invasive recurrence, 1 experienced locoregional failure, and 3 experienced distant metastasis. The overall and cancer-specific survival rates at 3 years were 61% and 71%, respectively. Of the surviving patients, 75% have a disease-free and functioning bladder. All patients completed hypofractionated IMRT, and 19 patients tolerated all 4 cycles of chemotherapy. Acute grade 3 gastrointestinal or genitourinary toxicities occurred in only 4% of the patients, and acute grade 3 or 4 hematologic toxicities, liver toxicities, or both were experienced by 17% of the cohort. No patient experienced grade 4 gastrointestinal or genitourinary toxicity. Conclusions: Hypofractionated IMRT with concurrent radiosensitizing chemotherapy appears to be an effective and well-tolerated curative treatment strategy in the elderly population and should be considered for patients who are not candidates for cystectomy or who wish to avoid

  3. The in vitro immunogenic potential of caspase-3 proficient breast cancer cells with basal low immunogenicity is increased by hypofractionated irradiation.

    Science.gov (United States)

    Kötter, Bernhard; Frey, Benjamin; Winderl, Markus; Rubner, Yvonne; Scheithauer, Heike; Sieber, Renate; Fietkau, Rainer; Gaipl, Udo S

    2015-09-17

    Radiotherapy is an integral part of breast cancer treatment. Immune activating properties of especially hypofractionated irradiation are in the spotlight of clinicians, besides the well-known effects of radiotherapy on cell cycle and the reduction of the clonogenic potential of tumor cells. Especially combination of radiotherapy with further immune stimulation induces immune-mediated anti-tumor responses. We therefore examined whether hypofractionated irradiation alone or in combination with hyperthermia as immune stimulants is capable of inducing breast cancer cells with immunogenic potential. Clonogenic assay, AnnexinA5-FITC/Propidium iodide assay and ELISA analyses of heat shock protein 70 and high mobility group box 1 protein were applied to characterize colony forming capability, cell death induction, cell death forms and release of danger signals by breast cancer cells in response to hypofractionated radiation (4x4Gy, 6x3Gy) alone and in combination with hyperthermia (41.5 °C for 1 h). Caspase-3 deficient, hormone receptor positive, p53 wild type MCF-7 and caspase-3 intact, hormone receptor negative, p53 mutated MDA-MB231 breast cancer cells, the latter in absence or presence of the pan-caspase inhibitor zVAD-fmk, were used. Supernatants of the treated tumor cells were analyzed for their potential to alter the surface expression of activation markers on human-monocyte-derived dendritic cells. Irradiation reduced the clonogenicity of caspase deficient MCF-7 cells more than of MDA-B231 cells. In contrast, higher amounts of apoptotic and necrotic cells were induced in MDA-B231 cells after single irradiation with 4Gy, 10Gy, or 20Gy or after hypofractionated irradiation with 4x4Gy or 6x3Gy. MDA-B231 cells consecutively released higher amounts of Hsp70 and HMGB1 after hypofractionated irradiation. However, only the release of Hsp70 was further increased by hyperthermia. Both, apoptosis induction and release of the danger signals, was dependent on caspase-3. Only

  4. Clinical Outcomes of Image Guided Adaptive Hypofractionated Weekly Radiation Therapy for Bladder Cancer in Patients Unsuitable for Radical Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Hafeez, Shaista, E-mail: shaista.hafeez@icr.ac.uk [The Institute of Cancer Research, London (United Kingdom); The Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); McDonald, Fiona; Lalondrelle, Susan [The Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); McNair, Helen; Warren-Oseni, Karole; Jones, Kelly [The Institute of Cancer Research, London (United Kingdom); The Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Harris, Victoria [The Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Taylor, Helen; Khoo, Vincent [The Royal Marsden NHS Foundation Trust, London (United Kingdom); Thomas, Karen [The Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Hansen, Vibeke; Dearnaley, David; Horwich, Alan; Huddart, Robert [The Institute of Cancer Research, London (United Kingdom); The Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom)

    2017-05-01

    Purpose and Objectives: We report on the clinical outcomes of a phase 2 study assessing image guided hypofractionated weekly radiation therapy in bladder cancer patients unsuitable for radical treatment. Methods and Materials: Fifty-five patients with T2-T4aNx-2M0-1 bladder cancer not suitable for cystectomy or daily radiation therapy treatment were recruited. A “plan of the day” radiation therapy approach was used, treating the whole (empty) bladder to 36 Gy in 6 weekly fractions. Acute toxicity was assessed weekly during radiation therapy, at 6 and 12 weeks using the Common Terminology Criteria for Adverse Events version 3.0. Late toxicity was assessed at 6 months and 12 months using Radiation Therapy Oncology Group grading. Cystoscopy was used to assess local control at 3 months. Cumulative incidence function was used to determine local progression at 1 at 2 years. Death without local progression was treated as a competing risk. Overall survival was estimated using the Kaplan-Meier method. Results: Median age was 86 years (range, 68-97 years). Eighty-seven percent of patients completed their prescribed course of radiation therapy. Genitourinary and gastrointestinal grade 3 acute toxicity was seen in 18% (10/55) and 4% (2/55) of patients, respectively. No grade 4 genitourinary or gastrointestinal toxicity was seen. Grade ≥3 late toxicity (any) at 6 and 12 months was seen in 6.5% (2/31) and 4.3% (1/23) of patients, respectively. Local control after radiation therapy was 92% of assessed patients (60% total population). Cumulative incidence of local progression at 1 year and 2 years for all patients was 7% (95% confidence interval [CI] 2%-17%) and 17% (95% CI 8%-29%), respectively. Overall survival at 1 year was 63% (95% CI 48%-74%). Conclusion: Hypofractionated radiation therapy delivered weekly with a plan of the day approach offers good local control with acceptable toxicity in a patient population not suitable for radical bladder treatment.

  5. Clinical Outcomes of Image Guided Adaptive Hypofractionated Weekly Radiation Therapy for Bladder Cancer in Patients Unsuitable for Radical Treatment

    International Nuclear Information System (INIS)

    Hafeez, Shaista; McDonald, Fiona; Lalondrelle, Susan; McNair, Helen; Warren-Oseni, Karole; Jones, Kelly; Harris, Victoria; Taylor, Helen; Khoo, Vincent; Thomas, Karen; Hansen, Vibeke; Dearnaley, David; Horwich, Alan; Huddart, Robert

    2017-01-01

    Purpose and Objectives: We report on the clinical outcomes of a phase 2 study assessing image guided hypofractionated weekly radiation therapy in bladder cancer patients unsuitable for radical treatment. Methods and Materials: Fifty-five patients with T2-T4aNx-2M0-1 bladder cancer not suitable for cystectomy or daily radiation therapy treatment were recruited. A “plan of the day” radiation therapy approach was used, treating the whole (empty) bladder to 36 Gy in 6 weekly fractions. Acute toxicity was assessed weekly during radiation therapy, at 6 and 12 weeks using the Common Terminology Criteria for Adverse Events version 3.0. Late toxicity was assessed at 6 months and 12 months using Radiation Therapy Oncology Group grading. Cystoscopy was used to assess local control at 3 months. Cumulative incidence function was used to determine local progression at 1 at 2 years. Death without local progression was treated as a competing risk. Overall survival was estimated using the Kaplan-Meier method. Results: Median age was 86 years (range, 68-97 years). Eighty-seven percent of patients completed their prescribed course of radiation therapy. Genitourinary and gastrointestinal grade 3 acute toxicity was seen in 18% (10/55) and 4% (2/55) of patients, respectively. No grade 4 genitourinary or gastrointestinal toxicity was seen. Grade ≥3 late toxicity (any) at 6 and 12 months was seen in 6.5% (2/31) and 4.3% (1/23) of patients, respectively. Local control after radiation therapy was 92% of assessed patients (60% total population). Cumulative incidence of local progression at 1 year and 2 years for all patients was 7% (95% confidence interval [CI] 2%-17%) and 17% (95% CI 8%-29%), respectively. Overall survival at 1 year was 63% (95% CI 48%-74%). Conclusion: Hypofractionated radiation therapy delivered weekly with a plan of the day approach offers good local control with acceptable toxicity in a patient population not suitable for radical bladder treatment.

  6. Hypofractionated radiotherapy for localized prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hoecht, Stefan [Xcare Gruppe, Radiologie, Nuklearmedizin und Strahlentherapie, Saarlouis (Germany); Aebersold, Daniel M. [University of Bern, Universitaetsklinik fuer Radio-Onkologie, Inselspital, Bern (Switzerland); Albrecht, Clemens [Universitaetsklinikum der Paracelsus Medizinischen Privatuniversitaet, Klinik fuer Radioonkologie und Gemeinschaftspraxis fuer Strahlentherapie, Klinikum Nuernberg Nord, Nuremberg (Germany); Boehmer, Dirk [Charite Universitaetsmedizin, Klinik fuer Radioonkologie und Strahlentherapie, Berlin (Germany); Flentje, Michael [Universitaetsklinikum Wuerzburg, Klinik und Poliklinik fuer Strahlentherapie, Wuerzburg (Germany); Ganswindt, Ute [Ludwig-Maximilians-Universitaet Muenchen, Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie, Munich (Germany); Hoelscher, Tobias [Universitaetsklinikum Carl Gustav Carus, Technische Universitaet Dresden, Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie, Dresden (Germany); Martin, Thomas [Klinikum Bremen-Mitte, Klinik fuer Strahlentherapie und Radioonkologie, Bremen (Germany); Sedlmayer, Felix [Universitaetsklinikum der Paracelsus Medizinischen Privatuniversitaet, Universitaetsklinik fuer Radiotherapie und Radio-Onkologie, Landeskrankenhaus, Salzburg (Austria); Wenz, Frederik [Universitaetsmedizin Mannheim, Universitaet Heidelberg, Klinik fuer Strahlentherapie und Radioonkologie, Mannheim (Germany); Zips, Daniel [Universitaetsklinikum Tuebingen, Universitaetsklinik fuer Radioonkologie, Tuebingen (Germany); Wiegel, Thomas [Universitaetsklinikum Ulm, Abteilung Strahlentherapie, Ulm (Germany)

    2017-01-15

    This article gives an overview on the current status of hypofractionated radiotherapy in the treatment of prostate cancer with a special focus on the applicability in routine use. Based on a recently published systematic review the German Society of Radiation Oncology (DEGRO) expert panel added additional information that has become available since then and assessed the validity of the information on outcome parameters especially with respect to long-term toxicity and long-term disease control. Several large-scale trials on moderate hypofractionation with single doses from 2.4-3.4 Gy have recently finished recruiting or have published first results suggestive of equivalent outcomes although there might be a trend for increased short-term and possibly even long-term toxicity. Large phase 3 trials on extreme hypofractionation with single doses above 4.0 Gy are lacking and only very few prospective trials have follow-up periods covering more than just 2-3 years. Until the results on long-term follow-up of several well-designed phase 3 trials become available, moderate hypofractionation should not be used in routine practice without special precautions and without adherence to the highest quality standards and evidence-based dose fractionation regimens. Extreme hypofractionation should be restricted to prospective clinical trials. (orig.) [German] Diese Uebersichtsarbeit soll den aktuellen Status der hypofraktionierten Radiotherapie des Prostatakarzinoms mit dem Fokus auf die Anwendung in der Routinetherapie darstellen. Basierend auf einem kuerzlich erschienen systematischen Review zur Hypofraktionierung sind durch das DEGRO Expertengremium zusaetzliche, in der Zwischenzeit verfuegbar gewordene Informationen mit beruecksichtigt worden. Die Validitaet der Aussagen zu Ergebnissen wurde speziell im Hinblick auf die Langzeittoxizitaet und -erkrankungskontrolle bewertet. Mehrere grosse Phase-3-Studien zur moderaten Hypofraktionierung mit Dosen von 2,4-3,4 Gy pro Fraktion

  7. Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non-Small Cell Lung Cancer: Phase 1 Dose Escalation Trial

    Energy Technology Data Exchange (ETDEWEB)

    Westover, Kenneth D. [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Loo, Billy W. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Gerber, David E. [Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Iyengar, Puneeth; Choy, Hak [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Diehn, Maximilian [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Hughes, Randy; Schiller, Joan; Dowell, Jonathan [Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wardak, Zabi [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Sher, David [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Christie, Alana; Xie, Xian-Jin [Department of Clinical Science, Southwestern Medical Center, Dallas, Texas (United States); Corona, Irma [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Sharma, Akanksha [School of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wadsworth, Margaret E. [Radiation Oncology of Mississippi, Jackson, Mississippi (United States); Timmerman, Robert, E-mail: Robert.Timmerman@utsouthwestern.edu [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States)

    2015-09-01

    Purpose: Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. Methods and Materials: Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. Results: Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P=.24). The median overall survival was 6 months with no significant differences between dose levels (P=.59). Conclusions: Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long

  8. Comparing two strategies of dynamic intensity modulated radiation therapy (dIMRT with 3-dimensional conformal radiation therapy (3DCRT in the hypofractionated treatment of high-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Yartsev Slav

    2008-01-01

    Full Text Available Abstract Background To compare two strategies of dynamic intensity modulated radiation therapy (dIMRT with 3-dimensional conformal radiation therapy (3DCRT in the setting of hypofractionated high-risk prostate cancer treatment. Methods 3DCRT and dIMRT/Helical Tomotherapy(HT planning with 10 CT datasets was undertaken to deliver 68 Gy in 25 fractions (prostate and simultaneously delivering 45 Gy in 25 fractions (pelvic lymph node targets in a single phase. The paradigms of pelvic vessel targeting (iliac vessels with margin are used to target pelvic nodes and conformal normal tissue avoidance (treated soft tissues of the pelvis while limiting dose to identified pelvic critical structures were assessed compared to 3DCRT controls. Both dIMRT/HT and 3DCRT solutions were compared to each other using repeated measures ANOVA and post-hoc paired t-tests. Results When compared to conformal pelvic vessel targeting, conformal normal tissue avoidance delivered more homogenous PTV delivery (2/2 t-test comparisons; p dose, 1–3 Gy over 5/10 dose points; p Conclusion dIMRT/HT nodal and pelvic targeting is superior to 3DCRT in dose delivery and critical structure sparing in the setting of hypofractionation for high-risk prostate cancer. The pelvic targeting paradigm is a potential solution to deliver highly conformal pelvic radiation treatment in the setting of nodal location uncertainty in prostate cancer and other pelvic malignancies.

  9. High tech hypofractionation to optimise treatment

    DEFF Research Database (Denmark)

    Johansen, Jørgen

    2015-01-01

    Hypofractionation has lately been implemented as standard treatment in the adjuvant setting as well as in radical radiotherapy for various solid tumors such as in breast and lung carcinomas. Also for metastatic disease in the liver or brain, hypofractionated stereotactic radiotherapy has proven e...

  10. Global survival in patients with glioblastoma treated with hypofractionated radiation therapy at Hospital Mexico of Costa Rica during the period from January 2010 to February 2013

    International Nuclear Information System (INIS)

    Ramirez Zamora, Juliana

    2014-01-01

    Survival is analyzed in patients with glioblastoma treated with hypofractionated radiation therapy at Hospital Mexico. The characteristics of the patients are determined within the study. Survival is stableshed in patients who have received hypofractionated regimen. Functional status according to ECOG scale and Karnofsky index is known prior to radiotherapy. The degree of resection to which these patients were submitted is diagnosed before being referred to radiotherapy. The RPA scale adapted from the EORTC of patients is related to overall survival. The mean survival time of the patients have been 5,8 months, and a greater overall survival in the first 6 months. Survival has been more favorable for patients with predicted RPA IV, those older than 60 years and with a degree of complete resection [es

  11. A Phase 2 Trial of Once-Weekly Hypofractionated Breast Irradiation: First Report of Acute Toxicity, Feasibility, and Patient Satisfaction

    Energy Technology Data Exchange (ETDEWEB)

    Dragun, Anthony E., E-mail: aedrag01@louisville.edu [Department of Radiation Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Quillo, Amy R. [Department of Surgical Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Riley, Elizabeth C. [Department of Medical Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Roberts, Teresa L.; Hunter, Allison M. [Department of Radiation Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Rai, Shesh N. [Department of Biostatistics and Epidemiology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Callender, Glenda G. [Department of Surgical Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Jain, Dharamvir [Department of Medical Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); McMasters, Kelly M. [Department of Surgical Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Spanos, William J. [Department of Radiation Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States)

    2013-03-01

    Purpose: To report on early results of a single-institution phase 2 trial of a 5-fraction, once-weekly radiation therapy regimen for patients undergoing breast-conserving surgery (BCS). Methods and Materials: Patients who underwent BCS for American Joint Committee on Cancer stage 0, I, or II breast cancer with negative surgical margins were eligible to receive whole breast radiation therapy to a dose of 30 Gy in 5 weekly fractions of 6 Gy with or without an additional boost. Elective nodal irradiation was not permitted. There were no restrictions on breast size or the use of cytotoxic chemotherapy for otherwise eligible patients. Patients were assessed at baseline, treatment completion, and at first posttreatment follow-up to assess acute toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and quality of life (European Organization for Research and Treatment of Cancer QLQ-BR23). Results: Between January and September 2011, 42 eligible patients underwent weekly hypofractionated breast irradiation immediately following BCS (69.0%) or at the conclusion of cytotoxic chemotherapy (31.0%). The rates of grade ≥2 radiation-induced dermatitis, pain, fatigue, and breast edema were 19.0%, 11.9%, 9.5%, and 2.4%, respectively. Only 1 grade 3 toxicity—pain requiring a course of narcotic analgesics—was observed. One patient developed a superficial cellulitis (grade 2), which resolved with the use of oral antibiotics. Patient-reported moderate-to-major breast symptoms (pain, swelling, and skin problems), all decreased from baseline through 1 month, whereas breast sensitivity remained stable over the study period. Conclusions: The tolerance of weekly hypofractionated breast irradiation compares well with recent reports of daily hypofractionated whole-breast irradiation schedules. The regimen appears feasible and cost-effective. Additional follow-up with continued accrual is needed to assess late toxicity, cosmesis, and disease-specific outcomes.

  12. A Phase 2 Trial of Once-Weekly Hypofractionated Breast Irradiation: First Report of Acute Toxicity, Feasibility, and Patient Satisfaction

    International Nuclear Information System (INIS)

    Dragun, Anthony E.; Quillo, Amy R.; Riley, Elizabeth C.; Roberts, Teresa L.; Hunter, Allison M.; Rai, Shesh N.; Callender, Glenda G.; Jain, Dharamvir; McMasters, Kelly M.; Spanos, William J.

    2013-01-01

    Purpose: To report on early results of a single-institution phase 2 trial of a 5-fraction, once-weekly radiation therapy regimen for patients undergoing breast-conserving surgery (BCS). Methods and Materials: Patients who underwent BCS for American Joint Committee on Cancer stage 0, I, or II breast cancer with negative surgical margins were eligible to receive whole breast radiation therapy to a dose of 30 Gy in 5 weekly fractions of 6 Gy with or without an additional boost. Elective nodal irradiation was not permitted. There were no restrictions on breast size or the use of cytotoxic chemotherapy for otherwise eligible patients. Patients were assessed at baseline, treatment completion, and at first posttreatment follow-up to assess acute toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and quality of life (European Organization for Research and Treatment of Cancer QLQ-BR23). Results: Between January and September 2011, 42 eligible patients underwent weekly hypofractionated breast irradiation immediately following BCS (69.0%) or at the conclusion of cytotoxic chemotherapy (31.0%). The rates of grade ≥2 radiation-induced dermatitis, pain, fatigue, and breast edema were 19.0%, 11.9%, 9.5%, and 2.4%, respectively. Only 1 grade 3 toxicity—pain requiring a course of narcotic analgesics—was observed. One patient developed a superficial cellulitis (grade 2), which resolved with the use of oral antibiotics. Patient-reported moderate-to-major breast symptoms (pain, swelling, and skin problems), all decreased from baseline through 1 month, whereas breast sensitivity remained stable over the study period. Conclusions: The tolerance of weekly hypofractionated breast irradiation compares well with recent reports of daily hypofractionated whole-breast irradiation schedules. The regimen appears feasible and cost-effective. Additional follow-up with continued accrual is needed to assess late toxicity, cosmesis, and disease-specific outcomes

  13. Rise and fall of hypofractionation in clinical radiotherapy in the 20th century

    International Nuclear Information System (INIS)

    Friberg, S.; Ruden, B. I.

    2007-01-01

    The purpose of this article is to review of the use of hypofractionated radiotherapy during the last two centuries. We define hypofractionation as any treatment where the individual fraction exceeds 2.0 Gray (Gy). The number of fractions is disregarded. The struggle of the early radiotherapists, the slow acceptance of fractionation, and the battle between the German and the French schools are reviewed. The early mathematical formulae of biological effects radiation are described and commented on. The paramount contribution in radiotherapy by British scientists gave rise to a new science: radiobiology. This branch had now matured into an exact discipline, separate from, and yet utterly depending on, its 100 years old sibling: Diagnostic Radiology. The come-back and fall of hypofractionation during two centuries is described, and set in relation to the treatment philosophy of the corresponding period. Injuries are described, and the long latency period for late reactions pointed out. Some of the legal aspects of the injuries are discussed. The come-back of hypofractionation - twice declared dead and buried the 20 th century - in the late 1990's is explained. The brilliant incorporation variability (α andβ) into mathematical exactness (the LQ-formula) has had, and will have a profound impact on clinical radiotherapy. (author)

  14. Stereotactic Hypofractionated Radiation Therapy as a Bridge to Transplantation for Hepatocellular Carcinoma: Clinical Outcome and Pathologic Correlation

    International Nuclear Information System (INIS)

    Katz, Alan W.; Chawla, Sheema; Qu, Zhenhong; Kashyap, Randeep; Milano, Michael T.; Hezel, Aram F.

    2012-01-01

    Purpose: We sought to determine efficacy, safety, and outcome of stereotactic hypofractionated radiation therapy (SHORT) as a suitable bridging therapy for patients awaiting liver transplantation (LT) for hepatocellular carcinoma (HCC). We also examined histological response to radiation in the resected or explanted livers. Methods and Materials: Between August 2007 and January 2009, 18 patients with 21 lesions received SHORT. A median total dose of 50 Gy was delivered in 10 fractions. Three patients underwent either chemoembolization (n = 1) or radiofrequency ablation (n = 2) prior to SHORT. Radiographic response was based on computed tomography evaluation at 3 months after SHORT. Histological response as a percentage of tumor necrosis was assessed by a quantitative morphometric method. Results: Six of 18 patients were delisted because of progression (n = 3) or other causes (n = 3). Twelve patients successfully underwent major hepatic resection (n = 1) or LT (n = 11) at a median follow-up of 6.3 months (range, 0.6–11.6 months) after completion of SHORT. No patient developed gastrointestinal toxicity Grade ≥3 or radiation-induced liver disease. Ten patients with 11 lesions were evaluable for pathological response. Two lesions had 100% necrosis, three lesions had ≥50% necrosis, four lesions had ≤50% necrosis, and two lesions had no necrosis. All patients were alive after LT and/or major hepatic resection at a median follow-up of 19.6 months. Conclusions: SHORT is an effective bridging therapy for patients awaiting LT for HCC. It provides excellent in-field control with minimal side effects, helps to downsize or stabilize tumors prior to LT, and achieves good pathological response.

  15. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

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    Yannam, Govardhana Rao [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Han, Bing [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an, Shaanxi (China); Setoyama, Kentaro [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamamoto, Toshiyuki [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Ito, Ryotaro; Brooks, Jenna M. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Guzman-Lepe, Jorge [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Galambos, Csaba [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Fong, Jason V. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Deutsch, Melvin; Quader, Mubina A. [Department of Radiation Oncology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamanouchi, Kosho [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kabarriti, Rafi; Mehta, Keyur [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Soto-Gutierrez, Alejandro [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); and others

    2014-02-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.

  16. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    International Nuclear Information System (INIS)

    Yannam, Govardhana Rao; Han, Bing; Setoyama, Kentaro; Yamamoto, Toshiyuki; Ito, Ryotaro; Brooks, Jenna M.; Guzman-Lepe, Jorge; Galambos, Csaba; Fong, Jason V.; Deutsch, Melvin; Quader, Mubina A.; Yamanouchi, Kosho; Kabarriti, Rafi; Mehta, Keyur; Soto-Gutierrez, Alejandro

    2014-01-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury

  17. Four-Week Course of Radiation for Breast Cancer Using Hypofractionated Intensity Modulated Radiation Therapy With an Incorporated Boost

    International Nuclear Information System (INIS)

    Freedman, Gary M.; Anderson, Penny R.; Goldstein, Lori J.; Ma Changming; Li Jinsheng; Swaby, Ramona F.; Litwin, Samuel; Watkins-Bruner, Deborah; Sigurdson, Elin R.; Morrow, Monica

    2007-01-01

    Purpose: Standard radiation for early breast cancer requires daily treatment for 6 to 7 weeks. This is an inconvenience to many women, and for some a barrier for breast conservation. We present the acute toxicity of a 4-week course of hypofractionated radiation. Methods and Materials: A total of 75 patients completed radiation on a Phase II trial approved by the hospital institutional review board. Eligibility criteria were broad to include any patient normally eligible for standard radiation: age ≥18 years, invasive or in situ cancer, American Joint Committee on Cancer Stage 0 to II, breast-conserving surgery, and any systemic therapy not given concurrently. The median age was 52 years (range, 31-81 years). Of the patients, 15% had ductal carcinoma in situ, 67% T1, and 19% T2; 71% were N0, 17% N1, and 12% NX. Chemotherapy was given before radiation in 44%. Using photon intensity-modulated radiation therapy and incorporated electron beam boost, the whole breast received 45 Gy and the lumpectomy bed 56 Gy in 20 treatments over 4 weeks. Results: The maximum acute skin toxicity by the end of treatment was Grade 0 in 9 patients (12%), Grade 1 in 49 (65%) and Grade 2 in 17 (23%). There was no Grade 3 or higher skin toxicity. After radiation, all Grade 2 toxicity had resolved by 6 weeks. Hematologic toxicity was Grade 0 in most patients except for Grade 1 neutropenia in 2 patients, and Grade 1 anemia in 11 patients. There were no significant differences in baseline vs. 6-week posttreatment patient-reported or physician-reported cosmetic scores. Conclusions: This 4-week course of postoperative radiation using intensity-modulated radiation therapy is feasible and is associated with acceptable acute skin toxicity and quality of life. Long-term follow-up data are needed. This radiation schedule may represent an alternative both to longer 6-week to 7-week standard whole-breast radiation and more radically shortened 1-week, partial-breast treatment schedules

  18. Reirradiation of head and neck cancer focusing on hypofractionated stereotactic body radiation therapy

    Directory of Open Access Journals (Sweden)

    Ogita Mikio

    2011-08-01

    Full Text Available Abstract Reirradiation is a feasible option for patients who do not otherwise have treatment options available. Depending on the location and extent of the tumor, reirradiation may be accomplished with external beam radiotherapy, brachytherapy, radiosurgery, or intensity modulated radiation therapy (IMRT. Although there has been limited experience with hypofractionated stereotactic radiotherapy (hSRT, it may have the potential for curative or palliative treatment due to its advanced precision technology, particularly for limited small lesion. On the other hand, severe late adverse reactions are anticipated with reirradiation than with initial radiation therapy. The risk of severe late complications has been reported to be 20- 40% and is related to prior radiotherapy dose, primary site, retreatment radiotherapy dose, treatment volume, and technique. Early researchers have observed lethal bleeding in such patients up to a rate of 14%. Recently, similar rate of 10-15% was observed for fatal bleeding with use of modern hSRT like in case of carotid blowout syndrome. To determine the feasibility and efficacy of reirradiation using modern technology, we reviewed the pertinent literature. The potentially lethal side effects should be kept in mind when reirradiation by hSRT is considered for treatment, and efforts should be made to minimize the risk in any future investigations.

  19. Reirradiation of head and neck cancer focusing on hypofractionated stereotactic body radiation therapy

    International Nuclear Information System (INIS)

    Yamazaki, Hideya; Kodani, Naohiro; Ogita, Mikio; Sato, Kengo; Himei, Kengo

    2011-01-01

    Reirradiation is a feasible option for patients who do not otherwise have treatment options available. Depending on the location and extent of the tumor, reirradiation may be accomplished with external beam radiotherapy, brachytherapy, radiosurgery, or intensity modulated radiation therapy (IMRT). Although there has been limited experience with hypofractionated stereotactic radiotherapy (hSRT), it may have the potential for curative or palliative treatment due to its advanced precision technology, particularly for limited small lesion. On the other hand, severe late adverse reactions are anticipated with reirradiation than with initial radiation therapy. The risk of severe late complications has been reported to be 20- 40% and is related to prior radiotherapy dose, primary site, retreatment radiotherapy dose, treatment volume, and technique. Early researchers have observed lethal bleeding in such patients up to a rate of 14%. Recently, similar rate of 10-15% was observed for fatal bleeding with use of modern hSRT like in case of carotid blowout syndrome. To determine the feasibility and efficacy of reirradiation using modern technology, we reviewed the pertinent literature. The potentially lethal side effects should be kept in mind when reirradiation by hSRT is considered for treatment, and efforts should be made to minimize the risk in any future investigations

  20. Adjuvant radiotherapy for cutaneous melanoma: Comparing hypofractionation to conventional fractionation

    International Nuclear Information System (INIS)

    Chang, Daniel T.; Amdur, Robert J.; Morris, Christopher G. M.S.; Mendenhall, William M.

    2006-01-01

    Purpose: To examine locoregional control after adjuvant radiotherapy (RT) for cutaneous melanoma and compare outcomes between conventional fractionation and hypofractionation. Methods and Materials: Between January 1980 and June 2004, 56 patients with high-risk disease were treated with adjuvant RT. Indications for RT included: recurrent disease, cervical lymph node involvement, lymph nodes >3 cm, more than three lymph nodes involved, extracapsular extension, gross residual disease, close or positive margins, or satellitosis. Hypofractionation was used in 41 patients (73%) and conventional fractionation was used in 15 patients (27%). Results: The median age was 61 years (21->90). The median follow-up among living patients was 4.4 years (range, 0.6-14.4 years). The primary site was located in the head and neck in 49 patients (87%) and below the clavicles in 7 patients (13%). There were 7 in-field locoregional failures (12%), 3 out-of-field regional failures (5%), and 24 (43%) distant failures. The 5-year in-field locoregional control (ifLRC) and freedom from distant metastases (FFDM) rates were 87% and 43%, respectively. The 5-year cause-specific (CSS) and overall survival (OS) was 57% and 46%, respectively. The only factor associated with ifLRC was satellitosis (p = 0.0002). Nodal involvement was the only factor associated with FFDM (p = 0.0007), CSS (p = 0.0065), and OS (p = 0.016). Two patients (4%) who experienced severe late complications, osteoradionecrosis of the temporal bone and radiation plexopathy, and both received hypofractionation (5%). Conclusions: Although surgery and adjuvant RT provides excellent locoregional control, distant metastases remain the major cause of mortality. Hypofractionation and conventional fractionation are equally efficacious

  1. WE-F-304-00: Outcomes of Hypofractionated Treatments - Results of the WGSBRT

    International Nuclear Information System (INIS)

    2015-01-01

    Stereotactic Body Radiation Therapy (SBRT) was introduced clinically more than twenty years ago, and many subsequent publications have reported safety and efficacy data. The AAPM Working Group on Biological Effects of Hypofractionated Radiotherapy/SBRT (WGSBRT) extracted published treatment outcomes data from extensive literature searches to summarize and construct tumor control probability (TCP) and normal tissue complication probability (NTCP) models for six anatomical regions: Cranial, Head and Neck, Thoracic, Abdominal, Pelvic, and Spinal. In this session, we present the WGSBRT’s work for cranial sites, and recurrent head and neck cancer. From literature-based data and associated models, guidelines to aid with safe and effective hypofractionated radiotherapy treatment are being determined. Further, the ability of existing and proposed radiobiological models to fit these data is considered as to the ability to distinguish between the linear-quadratic and alternative radiobiological models such as secondary cell death from vascular damage, immunogenic, or bystander effects. Where appropriate, specific model parameters are estimated. As described in “The lessons of QUANTEC,” (1), lack of adequate reporting standards continues to limit the amount of useful quantitative information that can be extracted from peer-reviewed publications. Recommendations regarding reporting standards are considered, to enable such reviews to achieve more complete characterization of clinical outcomes. 1 Jackson A, Marks LB, Bentzen SM, Eisbruch A, Yorke ED, Ten Haken RK, Constine LS, Deasy JO. The lessons of QUANTEC: recommendations for reporting and gathering data on dose-volume dependencies of treatment outcome. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S155–60. Learning Objectives: Describe the techniques, types of cancer and dose schedules used in treating recurrent H&N cancers with SBRT List the radiobiological models that compete with the linear-quadratic model

  2. WE-F-304-03: Optic Nerve/Chiasm Hypofractionated SRS/SRT Dose Tolerance

    International Nuclear Information System (INIS)

    Milano, M.

    2015-01-01

    Stereotactic Body Radiation Therapy (SBRT) was introduced clinically more than twenty years ago, and many subsequent publications have reported safety and efficacy data. The AAPM Working Group on Biological Effects of Hypofractionated Radiotherapy/SBRT (WGSBRT) extracted published treatment outcomes data from extensive literature searches to summarize and construct tumor control probability (TCP) and normal tissue complication probability (NTCP) models for six anatomical regions: Cranial, Head and Neck, Thoracic, Abdominal, Pelvic, and Spinal. In this session, we present the WGSBRT’s work for cranial sites, and recurrent head and neck cancer. From literature-based data and associated models, guidelines to aid with safe and effective hypofractionated radiotherapy treatment are being determined. Further, the ability of existing and proposed radiobiological models to fit these data is considered as to the ability to distinguish between the linear-quadratic and alternative radiobiological models such as secondary cell death from vascular damage, immunogenic, or bystander effects. Where appropriate, specific model parameters are estimated. As described in “The lessons of QUANTEC,” (1), lack of adequate reporting standards continues to limit the amount of useful quantitative information that can be extracted from peer-reviewed publications. Recommendations regarding reporting standards are considered, to enable such reviews to achieve more complete characterization of clinical outcomes. 1 Jackson A, Marks LB, Bentzen SM, Eisbruch A, Yorke ED, Ten Haken RK, Constine LS, Deasy JO. The lessons of QUANTEC: recommendations for reporting and gathering data on dose-volume dependencies of treatment outcome. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S155–60. Learning Objectives: Describe the techniques, types of cancer and dose schedules used in treating recurrent H&N cancers with SBRT List the radiobiological models that compete with the linear-quadratic model

  3. WE-F-304-03: Optic Nerve/Chiasm Hypofractionated SRS/SRT Dose Tolerance

    Energy Technology Data Exchange (ETDEWEB)

    Milano, M. [University of Rochester Medical Center (United States)

    2015-06-15

    Stereotactic Body Radiation Therapy (SBRT) was introduced clinically more than twenty years ago, and many subsequent publications have reported safety and efficacy data. The AAPM Working Group on Biological Effects of Hypofractionated Radiotherapy/SBRT (WGSBRT) extracted published treatment outcomes data from extensive literature searches to summarize and construct tumor control probability (TCP) and normal tissue complication probability (NTCP) models for six anatomical regions: Cranial, Head and Neck, Thoracic, Abdominal, Pelvic, and Spinal. In this session, we present the WGSBRT’s work for cranial sites, and recurrent head and neck cancer. From literature-based data and associated models, guidelines to aid with safe and effective hypofractionated radiotherapy treatment are being determined. Further, the ability of existing and proposed radiobiological models to fit these data is considered as to the ability to distinguish between the linear-quadratic and alternative radiobiological models such as secondary cell death from vascular damage, immunogenic, or bystander effects. Where appropriate, specific model parameters are estimated. As described in “The lessons of QUANTEC,” (1), lack of adequate reporting standards continues to limit the amount of useful quantitative information that can be extracted from peer-reviewed publications. Recommendations regarding reporting standards are considered, to enable such reviews to achieve more complete characterization of clinical outcomes. 1 Jackson A, Marks LB, Bentzen SM, Eisbruch A, Yorke ED, Ten Haken RK, Constine LS, Deasy JO. The lessons of QUANTEC: recommendations for reporting and gathering data on dose-volume dependencies of treatment outcome. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S155–60. Learning Objectives: Describe the techniques, types of cancer and dose schedules used in treating recurrent H&N cancers with SBRT List the radiobiological models that compete with the linear-quadratic model

  4. WE-F-304-00: Outcomes of Hypofractionated Treatments - Results of the WGSBRT

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2015-06-15

    Stereotactic Body Radiation Therapy (SBRT) was introduced clinically more than twenty years ago, and many subsequent publications have reported safety and efficacy data. The AAPM Working Group on Biological Effects of Hypofractionated Radiotherapy/SBRT (WGSBRT) extracted published treatment outcomes data from extensive literature searches to summarize and construct tumor control probability (TCP) and normal tissue complication probability (NTCP) models for six anatomical regions: Cranial, Head and Neck, Thoracic, Abdominal, Pelvic, and Spinal. In this session, we present the WGSBRT’s work for cranial sites, and recurrent head and neck cancer. From literature-based data and associated models, guidelines to aid with safe and effective hypofractionated radiotherapy treatment are being determined. Further, the ability of existing and proposed radiobiological models to fit these data is considered as to the ability to distinguish between the linear-quadratic and alternative radiobiological models such as secondary cell death from vascular damage, immunogenic, or bystander effects. Where appropriate, specific model parameters are estimated. As described in “The lessons of QUANTEC,” (1), lack of adequate reporting standards continues to limit the amount of useful quantitative information that can be extracted from peer-reviewed publications. Recommendations regarding reporting standards are considered, to enable such reviews to achieve more complete characterization of clinical outcomes. 1 Jackson A, Marks LB, Bentzen SM, Eisbruch A, Yorke ED, Ten Haken RK, Constine LS, Deasy JO. The lessons of QUANTEC: recommendations for reporting and gathering data on dose-volume dependencies of treatment outcome. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S155–60. Learning Objectives: Describe the techniques, types of cancer and dose schedules used in treating recurrent H&N cancers with SBRT List the radiobiological models that compete with the linear-quadratic model

  5. Impact of Fraction Size on Lung Radiation Toxicity: Hypofractionation may be Beneficial in Dose Escalation of Radiotherapy for Lung Cancers

    International Nuclear Information System (INIS)

    Jin Jinyue; Kong Fengming; Chetty, Indrin J.; Ajlouni, Munther; Ryu, Samuel; Ten Haken, Randall; Movsas, Benjamin

    2010-01-01

    Purpose: To assess how fraction size impacts lung radiation toxicity and therapeutic ratio in treatment of lung cancers. Methods and Materials: The relative damaged volume (RDV) of lung was used as the endpoint in the comparison of various fractionation schemes with the same normalized total dose (NTD) to the tumor. The RDV was computed from the biologically corrected lung dose-volume histogram (DVH), with an α/β ratio of 3 and 10 for lung and tumor, respectively. Two different (linear and S-shaped) local dose-effect models that incorporated the concept of a threshold dose effect with a single parameter D L50 (dose at 50% local dose effect) were used to convert the DVH into the RDV. The comparison was conducted using four representative DVHs at different NTD and D L50 values. Results: The RDV decreased with increasing dose/fraction when the NTD was larger than a critical dose (D CR ) and increased when the NTD was less than D CR . The D CR was 32-50 Gy and 58-87 Gy for a small tumor (11 cm 3 ) for the linear and S-shaped local dose-effect models, respectively, when D L50 was 20-30 Gy. The D CR was 66-97 Gy and 66-99 Gy, respectively, for a large tumor (266 cm 3 ). Hypofractionation was preferred for small tumors and higher NTDs, and conventional fractionation was better for large tumors and lower NTDs. Hypofractionation might be beneficial for intermediate-sized tumors when NTD = 80-90 Gy, especially if the D L50 is small (20 Gy). Conclusion: This computational study demonstrated that hypofractionated stereotactic body radiotherapy is a better regimen than conventional fractionation in lung cancer patients with small tumors and high doses, because it generates lower RDV when the tumor NTD is kept unchanged.

  6. Hematopoietic Stem and Progenitor Cell Migration After Hypofractionated Radiation Therapy in a Murine Model

    Energy Technology Data Exchange (ETDEWEB)

    Kane, Jonathan [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Krueger, Sarah A.; Dilworth, Joshua T.; Torma, John T.; Wilson, George D.; Marples, Brian [Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Madlambayan, Gerard J., E-mail: madlamba@oakland.edu [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States)

    2013-12-01

    Purpose: To characterize the recruitment of bone marrow (BM)-derived hematopoietic stem and progenitor cells (HSPCs) within tumor microenvironment after radiation therapy (RT) in a murine, heterotopic tumor model. Methods and Materials: Lewis lung carcinoma tumors were established in C57BL/6 mice and irradiated with 30 Gy given as 2 fractions over 2 days. Tumors were imaged with positron emission tomography/computed tomography (PET/CT) and measured daily with digital calipers. The HSPC and myelomonocytic cell content was assessed via immunofluorescent staining and flow cytometry. Functionality of tumor-associated HSPCs was verified in vitro using colony-forming cell assays and in vivo by rescuing lethally irradiated C57BL/6 recipients. Results: Irradiation significantly reduced tumor volumes and tumor regrowth rates compared with nonirradiated controls. The number of CD133{sup +} HSPCs present in irradiated tumors was higher than in nonirradiated tumors during all stages of regrowth. CD11b{sup +} counts were similar. PET/CT imaging and growth rate analysis based on standardized uptake value indicated that HSPC recruitment directly correlated to the extent of regrowth and intratumor cell activity after irradiation. The BM-derived tumor-associated HSPCs successfully formed hematopoietic colonies and engrafted irradiated mice. Finally, targeted treatment with a small animal radiation research platform demonstrated localized HSPC recruitment to defined tumor subsites exposed to radiation. Conclusions: Hypofractionated irradiation resulted in a pronounced and targeted recruitment of BM-derived HSPCs, possibly as a mechanism to promote tumor regrowth. These data indicate for the first time that radiation therapy regulates HSPC content within regrowing tumors.

  7. Hematopoietic Stem and Progenitor Cell Migration After Hypofractionated Radiation Therapy in a Murine Model

    International Nuclear Information System (INIS)

    Kane, Jonathan; Krueger, Sarah A.; Dilworth, Joshua T.; Torma, John T.; Wilson, George D.; Marples, Brian; Madlambayan, Gerard J.

    2013-01-01

    Purpose: To characterize the recruitment of bone marrow (BM)-derived hematopoietic stem and progenitor cells (HSPCs) within tumor microenvironment after radiation therapy (RT) in a murine, heterotopic tumor model. Methods and Materials: Lewis lung carcinoma tumors were established in C57BL/6 mice and irradiated with 30 Gy given as 2 fractions over 2 days. Tumors were imaged with positron emission tomography/computed tomography (PET/CT) and measured daily with digital calipers. The HSPC and myelomonocytic cell content was assessed via immunofluorescent staining and flow cytometry. Functionality of tumor-associated HSPCs was verified in vitro using colony-forming cell assays and in vivo by rescuing lethally irradiated C57BL/6 recipients. Results: Irradiation significantly reduced tumor volumes and tumor regrowth rates compared with nonirradiated controls. The number of CD133 + HSPCs present in irradiated tumors was higher than in nonirradiated tumors during all stages of regrowth. CD11b + counts were similar. PET/CT imaging and growth rate analysis based on standardized uptake value indicated that HSPC recruitment directly correlated to the extent of regrowth and intratumor cell activity after irradiation. The BM-derived tumor-associated HSPCs successfully formed hematopoietic colonies and engrafted irradiated mice. Finally, targeted treatment with a small animal radiation research platform demonstrated localized HSPC recruitment to defined tumor subsites exposed to radiation. Conclusions: Hypofractionated irradiation resulted in a pronounced and targeted recruitment of BM-derived HSPCs, possibly as a mechanism to promote tumor regrowth. These data indicate for the first time that radiation therapy regulates HSPC content within regrowing tumors

  8. Sci—Thur AM: YIS - 02: Radiogenomic Modeling of Normal Tissue Toxicities in Prostate Cancer Patients Receiving Hypofractionated Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Coates, J [Department of Oncology, Medical Physics Unit, McGill University Health Center, Montreal, QC (Canada); Jeyaseelan, K; Ybarra, N; David, M; Faria, S; Souhami, L; Cury, F; Duclos, M; El Naqa, I [Department of Oncology, Medical Physics Unit, McGill University Health Center, Montreal, QC (Canada); Department of Oncology, Radiation Oncology Division, McGill University Health Centre, Montreal, QC Canada (Canada)

    2014-08-15

    Inter-patient radiation sensitivity variability has recently been shown to have a genetic component. This genetic component may play a key role in explaining the fluctuating rates of radiation-induced toxicities (RITs). Single nucleotide polymorphisms (SNPs) have thus far yielded inconsistent results in delineating RITs while copy number variations (CNVs) have not yet been investigated for such purposes. We explore a radiogenomic modeling approach to investigate the association of CNVs and SNPs, along with clinical and dosimetric variables, in radiation induced rectal bleeding (RB) and erectile dysfunction (ED) in prostate cancer patients treated with curative hypofractionated irradiation. A cohort of 62 prostate cancer patients who underwent hypofractionated radiotherapy (66 Gy in 22 fractions) between 2002 to 2010 were retrospectively genotyped for CNV and SNP rs5489 in the xrcc1 DNA repair gene. Late toxicity rates for RB grade 2 and 3 and grade 3 alone were 29.0% and 12.9%, respectively. ED toxicity was found to be 62.9%. Radiogenomic model performance was evaluated using receiver operating characteristic area under the curve (AUC) and resampling by cross-validation. Binary variables were evaluated using Chi-squared contingency table analysis and multivariate models by Spearman's rank correlation coefficient (rs). Ten patients were found to have three copies of xrcc1 CNV (RB: χ{sup 2}=14.6, p<0.001 and ED: χ{sup 2}=4.88, p=0.0272) and twelve had heterozygous rs25489 SNP (RB: χ{sup 2}=0.278, p=0.599 and ED: χ{sup 2}=0.112, p=0.732). Radiogenomic modeling yielded significant, cross-validated NTCP models for RB (AUC=0.665) and ED (AUC=0.754). These results indicate that CNVs may be potential predictive biomarkers of both late ED and RB.

  9. The effect of hypofractionated radiation and magnetic nanoparticle hyperthermia on tumor immunogenicity and overall treatment response

    Science.gov (United States)

    Hoopes, P. Jack; Wagner, Robert J.; Song, Ailin; Osterberg, Bjorn; Gladstone, David J.; Bursey, Alicea A.; Fiering, Steven N.; Giustini, Andrew J.

    2017-02-01

    It is now known that many tumors develop molecular signals (immune checkpoint modulators) that inhibit an effective tumor immune response. New information also suggest that even well-known cancer treatment modalities such as radiation and hyperthermia generate potentially beneficial immune responses that have been blocked or mitigated by such immune checkpoints, or similar molecules. The cancer therapy challenge is to; a) identify these treatment-based immune signals (proteins, antigens, etc.); b) the treatment doses or regimens that produce them; and c) the mechanisms that block or have the potential to promote them. The goal of this preliminary study, using the B6 mouse - B16 tumor model, clinically relevant radiation doses and fractionation schemes (including those used clinically in hypofractionated radiation therapy), magnetic nanoparticle hyperthermia (mNPH) and sophisticated protein, immune and tumor growth analysis techniques and modulators, is to determine the effect of specific radiation or hyperthermia alone and combined on overall treatment efficacy and immunologic response mechanisms. Preliminary analysis suggests that radiation dose (10 Gy vs. 2 Gy) significantly alters the mechanism of cell death (apoptosis vs. mitosis vs. necrosis) and the resulting immunogenicity. Our hypothesis and data suggest this difference is protein/antigen and immune recognition-based. Similarly, our evidence suggest that radiation doses larger than the conventional 2 Gy dose and specific hyperthermia doses and techniques (including mNP hyperthermia treatment) can be immunologically different, and potentially superior to, the radiation and heat therapy regimens that are typically used in research and clinical practice.

  10. Treatment of dogs with oral melanoma by hypofractionated radiation therapy and platinum-based chemotherapy (1987-1997).

    Science.gov (United States)

    Freeman, Kim P; Hahn, Kevin A; Harris, F Dee; King, Glen K

    2003-01-01

    This retrospective study in 39 dogs with incompletely resected oral melanoma examined the efficacy of hypofractionated radiation therapy and platinum-containing chemotherapy. All dogs were completely staged, with the majority of dogs classified as stage 1. Dogs received 6 weekly fractions of 6-gray (Gy) megavoltage irradiation with a cobalt-60 unit or a 4-MeV (megaelectron volts) linear accelerator. Dogs received cisplatin (10-30 mg/m2 IV) or carboplatin (90 mg/m2 IV) chemotherapy 60 minutes before radiation delivery. Durations of local control, metastasis-free survival time, and overall survival time were recorded. By the Kaplan-Meier method, 15% of the dogs had local recurrence within a median time of 139 days. Fifty-one percent of the dogs developed metastatic disease within a median time of 311 days (range, 24-2, 163 days). Median survival time for all 39 dogs was 363 days. The combined use of chemotherapy and radiation therapy in this protocol provided local control consistent with previous studies. Low-dose chemotherapy was used with the intent of enhancing radiation therapy for the local control of an incompletely excised tumor. Survival times were longer than previously reported for dogs with oral malignant melanoma. Additional studies are required to determine whether these results were due to the effects of chemotherapy on microscopic disease or the enhanced local control provided by chemoradiation therapy.

  11. Comparing two strategies of dynamic intensity modulated radiation therapy (dIMRT) with 3-dimensional conformal radiation therapy (3DCRT) in the hypofractionated treatment of high-risk prostate cancer

    International Nuclear Information System (INIS)

    Yuen, Jasper; Rodrigues, George; Trenka, Kristina; Coad, Terry; Yartsev, Slav; D'Souza, David; Lock, Michael; Bauman, Glenn

    2008-01-01

    To compare two strategies of dynamic intensity modulated radiation therapy (dIMRT) with 3-dimensional conformal radiation therapy (3DCRT) in the setting of hypofractionated high-risk prostate cancer treatment. 3DCRT and dIMRT/Helical Tomotherapy(HT) planning with 10 CT datasets was undertaken to deliver 68 Gy in 25 fractions (prostate) and simultaneously delivering 45 Gy in 25 fractions (pelvic lymph node targets) in a single phase. The paradigms of pelvic vessel targeting (iliac vessels with margin are used to target pelvic nodes) and conformal normal tissue avoidance (treated soft tissues of the pelvis while limiting dose to identified pelvic critical structures) were assessed compared to 3DCRT controls. Both dIMRT/HT and 3DCRT solutions were compared to each other using repeated measures ANOVA and post-hoc paired t-tests. When compared to conformal pelvic vessel targeting, conformal normal tissue avoidance delivered more homogenous PTV delivery (2/2 t-test comparisons; p < 0.001), similar nodal coverage (8/8 t-test comparisons; p = ns), higher and more homogenous pelvic tissue dose (6/6 t-test comparisons; p < 0.03), at the cost of slightly higher critical structure dose (D dose , 1–3 Gy over 5/10 dose points; p < 0.03). The dIMRT/HT approaches were superior to 3DCRT in sparing organs at risk (22/24 t-test comparisons; p < 0.05). dIMRT/HT nodal and pelvic targeting is superior to 3DCRT in dose delivery and critical structure sparing in the setting of hypofractionation for high-risk prostate cancer. The pelvic targeting paradigm is a potential solution to deliver highly conformal pelvic radiation treatment in the setting of nodal location uncertainty in prostate cancer and other pelvic malignancies

  12. Hypofractionated stereotactic body radiation therapy as monotherapy for intermediate-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Ju Andrew W

    2013-01-01

    Full Text Available Abstract Background Hypofractionated stereotactic body radiation therapy (SBRT has been advanced as monotherapy for low-risk prostate cancer. We examined the dose distributions and early clinical outcomes using this modality for the treatment of intermediate-risk prostate cancer. Methods Forty-one sequential hormone-naïve intermediate-risk prostate cancer patients received 35–36.25 Gy of CyberKnife-delivered SBRT in 5 fractions. Radiation dose distributions were analyzed for coverage of potential microscopic ECE by measuring the distance from the prostatic capsule to the 33 Gy isodose line. PSA levels, toxicities, and quality of life (QOL measures were assessed at baseline and follow-up. Results All patients completed treatment with a mean coverage by the 33 Gy isodose line extending >5 mm beyond the prostatic capsule in all directions except posteriorly. Clinical responses were documented by a mean PSA decrease from 7.67 ng/mL pretreatment to 0.64 ng/mL at the median follow-up of 21 months. Forty patients remain free from biochemical progression. No Grade 3 or 4 toxicities were observed. Mean EPIC urinary irritation/obstruction and bowel QOL scores exhibited a transient decline post-treatment with a subsequent return to baseline. No significant change in sexual QOL was observed. Conclusions In this intermediate-risk patient population, an adequate radiation dose was delivered to areas of expected microscopic ECE in the majority of patients. Although prospective studies are needed to confirm long-term tumor control and toxicity, the short-term PSA response, biochemical relapse-free survival rate, and QOL in this interim analysis are comparable to results reported for prostate brachytherapy or external beam radiotherapy. Trial registration The Georgetown Institutional Review Board has approved this retrospective study (IRB 2009–510.

  13. Hypofractionated stereotactic body radiation therapy as monotherapy for intermediate-risk prostate cancer

    International Nuclear Information System (INIS)

    Ju, Andrew W; Lei, Siyuan; Suy, Simeng; Lynch, John H; Dritschilo, Anatoly; Collins, Sean P; Wang, Hongkun; Oermann, Eric K; Sherer, Benjamin A; Uhm, Sunghae; Chen, Viola J; Pendharkar, Arjun V; Hanscom, Heather N; Kim, Joy S

    2013-01-01

    Hypofractionated stereotactic body radiation therapy (SBRT) has been advanced as monotherapy for low-risk prostate cancer. We examined the dose distributions and early clinical outcomes using this modality for the treatment of intermediate-risk prostate cancer. Forty-one sequential hormone-naïve intermediate-risk prostate cancer patients received 35–36.25 Gy of CyberKnife-delivered SBRT in 5 fractions. Radiation dose distributions were analyzed for coverage of potential microscopic ECE by measuring the distance from the prostatic capsule to the 33 Gy isodose line. PSA levels, toxicities, and quality of life (QOL) measures were assessed at baseline and follow-up. All patients completed treatment with a mean coverage by the 33 Gy isodose line extending >5 mm beyond the prostatic capsule in all directions except posteriorly. Clinical responses were documented by a mean PSA decrease from 7.67 ng/mL pretreatment to 0.64 ng/mL at the median follow-up of 21 months. Forty patients remain free from biochemical progression. No Grade 3 or 4 toxicities were observed. Mean EPIC urinary irritation/obstruction and bowel QOL scores exhibited a transient decline post-treatment with a subsequent return to baseline. No significant change in sexual QOL was observed. In this intermediate-risk patient population, an adequate radiation dose was delivered to areas of expected microscopic ECE in the majority of patients. Although prospective studies are needed to confirm long-term tumor control and toxicity, the short-term PSA response, biochemical relapse-free survival rate, and QOL in this interim analysis are comparable to results reported for prostate brachytherapy or external beam radiotherapy. The Georgetown Institutional Review Board has approved this retrospective study (IRB 2009–510)

  14. Low Incidence of Fatigue after Hypofractionated Stereotactic Body Radiation Therapy (SBRT for Localized Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Chiranjeev eDash

    2012-10-01

    Full Text Available Background: Fatigue is a common side-effect of conventional prostate cancer radiation therapy. The increased delivery precision necessitated by the high dose per fraction of stereotactic body radiation therapy (SBRT offers the potential of reduce target volumes and hence the exposure of normal tissues to high radiation doses. Herein, we examine the level of fatigue associated with SBRT treatment.Methods: Forty patients with localized prostate cancer treated with hypofractionated SBRT, and a minimum of 12 months follow-up were included in this analysis. Self-reported fatigue and other quality of life measures were assessed at baseline and at 1, 3, 6, 9, and 12 months post-SBRT.Results: Mean levels of fatigue were elevated at 1 month post-SBRT compared to baseline values (p=0.02. Fatigue at the 3-month follow-up and later were higher but not statistically significantly different compared to baseline. African-American patients reported higher fatigue post-SBRT than Caucasian patients. Fatigue was correlated with hormonal symptoms as measured by the Expanded Prostate Cancer Index Composite (EPIC quality of life questionnaire, but not with urinary, bowel, or sexual symptoms. Age, co-morbidities, smoking, prostate specific antigen (PSA levels, testosterone levels, and tumor stage were not associated with fatigue. Conclusion: This is the first study to investigate fatigue as a side-effect of SBRT. In contrast to standard radiation therapy, results suggest SBRT-related fatigue is short-term rather than a long-term side effect of SBRT. These results also suggest post-SBRT fatigue to be a more frequent complication in African-Americans than Caucasians.

  15. Hypofractionated radiation therapy in the treatment of epidemic Kaposi sarcoma - A prospective randomized trial

    International Nuclear Information System (INIS)

    Singh, Niveditha B.; Lakier, Roy H.; Donde, Bernard

    2008-01-01

    Purpose: To compare a conventional fractionation regimen with a hypofractionated regimen in the treatment of Epidemic Kaposi sarcoma with radiation therapy. Materials and methods: Sixty patients were randomized to receive a standard regimen of 24 Gy in 12 fractions (ARM A) or the study regimen of 20 Gy in five fractions (ARM B). Radiation technique was individualized. Treatment response, local control and toxicity were recorded. Results: Thirty five sites were treated in ARM A and 30 sites in ARM B. Treatment arms were similar for gender, ECOG performance score, treated site, antiretroviral therapy usage, T stage, I stage and S stage. The overall survival using the Kaplan Meier method was 37% at 1 year. Complete responses were recorded at 28 sites (13 Arm A, 15 Arm B), partial responses at 19 sites (8 Arm A, 11 Arm B) and stable disease at three sites (2 Arm A, 1 Arm B). The mean time to maximum objective response was 3 months (range: 1-14 months). Response rates and local control were equal in the two arms (p = 0.73 and 0.77, respectively, log rank test). Acute skin toxicity (p = 0.77) and late skin toxicity (p = 0.24) were equal in the two arms. Conclusion: The two treatment regimens produced equivalent results for treatment response, local recurrence-free survival and toxicity

  16. Effect of image-guided hypofractionated stereotactic radiotherapy on peripheral non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Wang SW

    2016-08-01

    Full Text Available Shu-wen Wang,1 Juan Ren,1 Yan-li Yan,2 Chao-fan Xue,2 Li Tan,2 Xiao-wei Ma2 1Department of Radiotherapy, First Affiliated Hospital of Xian Jiaotong University, 2Medical School of Xian Jiaotong University, Xi’an, Shaanxi, People’s Republic of China Abstract: The objective of this study was to compare the effects of image-guided hypofractionated radiotherapy and conventional fractionated radiotherapy on non-small-cell lung cancer (NSCLC. Fifty stage- and age-matched cases with NSCLC were randomly divided into two groups (A and B. There were 23 cases in group A and 27 cases in group B. Image-guided radiotherapy (IGRT and stereotactic radiotherapy were conjugately applied to the patients in group A. Group A patients underwent hypofractionated radiotherapy (6–8 Gy/time three times per week, with a total dose of 64–66 Gy; group B received conventional fractionated radiotherapy, with a total dose of 68–70 Gy five times per week. In group A, 1-year and 2-year local failure survival rate and 1-year local failure-free survival rate were significantly higher than in group B (P<0.05. The local failure rate (P<0.05 and distant metastasis rate (P>0.05 were lower in group A than in group B. The overall survival rate of group A was significantly higher than that of group B (P=0.03, and the survival rate at 1 year was 87% vs 63%, (P<0.05. The median survival time of group A was longer than that of group B. There was no significant difference in the incidence of complications between the two groups (P>0.05. Compared with conventional fractionated radiation therapy, image-guided hypofractionated stereotactic radiotherapy in NSCLC received better treatment efficacy and showed good tolerability. Keywords: non-small-cell lung cancer, hypofractionated radiotherapy, stereotactic radiotherapy, segmentation, intensity-modulated radiotherapy, image-guided radiation therapy technology

  17. Norm- and hypo-fractionated radiotherapy is capable of activating human dendritic cells.

    Science.gov (United States)

    Kulzer, Lorenz; Rubner, Yvonne; Deloch, Lisa; Allgäuer, Andrea; Frey, Benjamin; Fietkau, Rainer; Dörrie, Jan; Schaft, Niels; Gaipl, Udo S

    2014-10-01

    Despite the transient immunosuppressive properties of local radiotherapy (RT), this classical treatment modality of solid tumors is capable of inducing immunostimulatory forms of tumor-cell death. The resulting 'immunotoxicity' in the tumor, but not in healthy tissues, may finally lead to immune-mediated destruction of the tumor. However, little is known about the best irradiation scheme in this setting. This study examines the immunological effects of differently irradiated human colorectal tumor cells on human monocyte-derived dendritic cells (DC). Human SW480 tumor cells were irradiated with a norm-fractionation scheme (5 × 2 Gy), a hypo-fractionated protocol (3 × 5 Gy), and with a high single irradiation dose (radiosurgery; 1 × 15 Gy). Subsequently, human immature DC (iDC) were co-incubated with supernatants (SN) of these differently treated tumor cells. Afterwards, DC were analyzed regarding the expression of maturation markers, the release of cytokines, and the potential to stimulate CD4(+) T-cells. The co-incubation of iDC with SN of tumor cells exposed to norm- or hypo-fractionated RT resulted in a significantly increased secretion of the immune activating cytokines IL-12p70, IL-8, IL-6, and TNFα, compared to iDC co-incubated with SN of tumor cells that received a high single irradiation dose or were not irradiated. In addition, DC-maturation markers CD80, CD83, and CD25 were also exclusively elevated after co-incubation with the SN of fractionated irradiated tumor cells. Furthermore, the SN of tumor cells that were irradiated with norm- or hypo-fractionated RT triggered iDC to stimulate CD4(+) T-cells not only in an allogenic, but also in an antigen-specific manner like mature DC. Collectively, these results demonstrate that norm- and hypo-fractionated RT induces a fast human colorectal tumor-cell death with immunogenic potential that can trigger DC maturation and activation in vitro. Such findings may contribute to the improvement of

  18. Prostate Hypofractionated Radiation Therapy: Injection of Hyaluronic Acid to Better Preserve The Rectal Wall

    International Nuclear Information System (INIS)

    Chapet, Olivier; Udrescu, Corina; Devonec, Marian; Tanguy, Ronan; Sotton, Marie-Pierre; Enachescu, Ciprian; Colombel, Marc; Azria, David; Jalade, Patrice; Ruffion, Alain

    2013-01-01

    Purpose: The aim of this study was to evaluate the contribution of an injection of hyaluronic acid (HA) between the rectum and the prostate for reducing the dose to the rectal wall in a hypofractionated irradiation for prostate cancer. Methods and Materials: In a phase 2 study, 10 cc of HA was injected between the rectum and prostate. For 16 patients, the same intensity modulated radiation therapy plan (62 Gy in 20 fractions) was optimized on 2 computed tomography scans: CT1 (before injection) and CT2 (after injection). Rectal parameters were compared: dose to 2.5 cc (D2.5), 5 cc (D5), 10 cc (D10), 15 cc (D15), and 20 cc (D20) of rectal wall and volume of rectum covered by the 90% isodose line (V90), 80% (V80), 70% (V70), 60% (V60), and 50% (V50). Results: The mean V90, V80, V70, V60, and V50 values were reduced by 73.8% (P<.0001), 55.7% (P=.0003), 43.0% (P=.007), 34% (P=.002), and 25% (P=.036), respectively. The average values of D2.5, D5, D10, D15, and D20 were reduced by 8.5 Gy (P<.0001), 12.3 Gy (P<.0001), 8.4 Gy (P=.005), 3.7 Gy (P=.026), and 1.2 Gy (P=.25), respectively. Conclusions: The injection of HA significantly limited radiation doses to the rectal wall

  19. Prostate Hypofractionated Radiation Therapy: Injection of Hyaluronic Acid to Better Preserve The Rectal Wall

    Energy Technology Data Exchange (ETDEWEB)

    Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Udrescu, Corina [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite (France); Devonec, Marian [Department of Urology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Tanguy, Ronan [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Sotton, Marie-Pierre [Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite (France); Enachescu, Ciprian [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Colombel, Marc [Department of Urology, Hopital Edouard Herriot, Lyon (France); Azria, David [Department of Radiation Oncology, Centre Val d' Aurelle, Montpellier (France); Jalade, Patrice [Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite (France); Ruffion, Alain [Department of Urology, Centre Hospitalier Lyon Sud, Pierre Benite (France)

    2013-05-01

    Purpose: The aim of this study was to evaluate the contribution of an injection of hyaluronic acid (HA) between the rectum and the prostate for reducing the dose to the rectal wall in a hypofractionated irradiation for prostate cancer. Methods and Materials: In a phase 2 study, 10 cc of HA was injected between the rectum and prostate. For 16 patients, the same intensity modulated radiation therapy plan (62 Gy in 20 fractions) was optimized on 2 computed tomography scans: CT1 (before injection) and CT2 (after injection). Rectal parameters were compared: dose to 2.5 cc (D2.5), 5 cc (D5), 10 cc (D10), 15 cc (D15), and 20 cc (D20) of rectal wall and volume of rectum covered by the 90% isodose line (V90), 80% (V80), 70% (V70), 60% (V60), and 50% (V50). Results: The mean V90, V80, V70, V60, and V50 values were reduced by 73.8% (P<.0001), 55.7% (P=.0003), 43.0% (P=.007), 34% (P=.002), and 25% (P=.036), respectively. The average values of D2.5, D5, D10, D15, and D20 were reduced by 8.5 Gy (P<.0001), 12.3 Gy (P<.0001), 8.4 Gy (P=.005), 3.7 Gy (P=.026), and 1.2 Gy (P=.25), respectively. Conclusions: The injection of HA significantly limited radiation doses to the rectal wall.

  20. Hypofractionated high-energy proton-beam irradiation is an alternative treatment for WHO grade I meningiomas.

    Science.gov (United States)

    Vlachogiannis, Pavlos; Gudjonsson, Olafur; Montelius, Anders; Grusell, Erik; Isacsson, Ulf; Nilsson, Kristina; Blomquist, Erik

    2017-12-01

    Radiation treatment is commonly employed in the treatment of meningiomas. The aim of this study was to evaluate the effectiveness and safety of hypofractionated high-energy proton therapy as adjuvant or primary treatment for WHO grade I meningiomas. A total of 170 patients who received irradiation with protons for grade I meningiomas between 1994 and 2007 were included in the study. The majority of the tumours were located at the skull base (n = 155). Eighty-four patients were treated post subtotal resection, 42 at tumour relapse and 44 with upfront radiotherapy after diagnosis based on the typical radiological image. Irradiation was given in a hypofractionated fashion (3-8 fractions, usually 5 or 6 Gy) with a mean dose of 21.9 Gy (range, 14-46 Gy). All patients were planned for follow-up with clinical controls and magnetic resonance imaging scans at 6 months and 1, 2, 3, 5, 7 and 10 years after treatment. The median follow-up time was 84 months. Age, gender, tumour location, Simpson resection grade and target volume were assessed as possible prognostic factors for post-irradiation tumour progression and radiation related complications. The actuarial 5- and 10-year progression-free survival rates were 93% and 85% respectively. Overall mortality rate was 13.5%, while disease-specific mortality was 1.7% (3/170 patients). Older patients and patients with tumours located in the middle cranial fossa had a lower risk for tumour progression. Radiation-related complications were seen in 16 patients (9.4%), with pituitary insufficiency being the most common. Tumour location in the anterior cranial fossa was the only factor that significantly increased the risk of complications. Hypofractionated proton-beam radiation therapy may be used particularly in the treatment of larger World Health Organisation grade I meningiomas not amenable to total surgical resection. Treatment is associated with high rates of long-term tumour growth control and acceptable risk for

  1. Five-year Local Control in a Phase II Study of Hypofractionated Intensity Modulated Radiation Therapy With an Incorporated Boost for Early Stage Breast Cancer

    International Nuclear Information System (INIS)

    Freedman, Gary M.; Anderson, Penny R.; Bleicher, Richard J.; Litwin, Samuel; Li Tianyu; Swaby, Ramona F.; Ma, Chang-Ming Charlie; Li Jinsheng; Sigurdson, Elin R.; Watkins-Bruner, Deborah; Morrow, Monica; Goldstein, Lori J.

    2012-01-01

    Purpose: Conventional radiation fractionation of 1.8-2 Gy per day for early stage breast cancer requires daily treatment for 6-7 weeks. We report the 5-year results of a phase II study of intensity modulated radiation therapy (IMRT), hypofractionation, and incorporated boost that shortened treatment time to 4 weeks. Methods and Materials: The study design was phase II with a planned accrual of 75 patients. Eligibility included patients aged ≥18 years, Tis-T2, stage 0-II, and breast conservation. Photon IMRT and an incorporated boost was used, and the whole breast received 2.25 Gy per fraction for a total of 45 Gy, and the tumor bed received 2.8 Gy per fraction for a total of 56 Gy in 20 treatments over 4 weeks. Patients were followed every 6 months for 5 years. Results: Seventy-five patients were treated from December 2003 to November 2005. The median follow-up was 69 months. Median age was 52 years (range, 31-81). Median tumor size was 1.4 cm (range, 0.1-3.5). Eighty percent of tumors were node negative; 93% of patients had negative margins, and 7% of patients had close (>0 and <2 mm) margins; 76% of cancers were invasive ductal type: 15% were ductal carcinoma in situ, 5% were lobular, and 4% were other histology types. Twenty-nine percent of patients 29% had grade 3 carcinoma, and 20% of patients had extensive in situ carcinoma; 11% of patients received chemotherapy, 36% received endocrine therapy, 33% received both, and 20% received neither. There were 3 instances of local recurrence for a 5-year actuarial rate of 2.7%. Conclusions: This 4-week course of hypofractionated radiation with incorporated boost was associated with excellent local control, comparable to historical results of 6-7 weeks of conventional whole-breast fractionation with sequential boost.

  2. Five-year Local Control in a Phase II Study of Hypofractionated Intensity Modulated Radiation Therapy With an Incorporated Boost for Early Stage Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Freedman, Gary M., E-mail: Gary.Freedman@uphs.upenn.edu [Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Anderson, Penny R. [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Bleicher, Richard J. [Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Litwin, Samuel; Li Tianyu [Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Swaby, Ramona F. [Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Ma, Chang-Ming Charlie; Li Jinsheng [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Sigurdson, Elin R. [Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Watkins-Bruner, Deborah [School of Nursing, Emory University, Atlanta, Georgia (United States); Morrow, Monica [Department of Surgical Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Goldstein, Lori J. [Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States)

    2012-11-15

    Purpose: Conventional radiation fractionation of 1.8-2 Gy per day for early stage breast cancer requires daily treatment for 6-7 weeks. We report the 5-year results of a phase II study of intensity modulated radiation therapy (IMRT), hypofractionation, and incorporated boost that shortened treatment time to 4 weeks. Methods and Materials: The study design was phase II with a planned accrual of 75 patients. Eligibility included patients aged {>=}18 years, Tis-T2, stage 0-II, and breast conservation. Photon IMRT and an incorporated boost was used, and the whole breast received 2.25 Gy per fraction for a total of 45 Gy, and the tumor bed received 2.8 Gy per fraction for a total of 56 Gy in 20 treatments over 4 weeks. Patients were followed every 6 months for 5 years. Results: Seventy-five patients were treated from December 2003 to November 2005. The median follow-up was 69 months. Median age was 52 years (range, 31-81). Median tumor size was 1.4 cm (range, 0.1-3.5). Eighty percent of tumors were node negative; 93% of patients had negative margins, and 7% of patients had close (>0 and <2 mm) margins; 76% of cancers were invasive ductal type: 15% were ductal carcinoma in situ, 5% were lobular, and 4% were other histology types. Twenty-nine percent of patients 29% had grade 3 carcinoma, and 20% of patients had extensive in situ carcinoma; 11% of patients received chemotherapy, 36% received endocrine therapy, 33% received both, and 20% received neither. There were 3 instances of local recurrence for a 5-year actuarial rate of 2.7%. Conclusions: This 4-week course of hypofractionated radiation with incorporated boost was associated with excellent local control, comparable to historical results of 6-7 weeks of conventional whole-breast fractionation with sequential boost.

  3. Feasibility and Acute Toxicity of Hypofractionated Radiation in Large-breasted Patients

    International Nuclear Information System (INIS)

    Dorn, Paige L.; Corbin, Kimberly S.; Al-Hallaq, Hania; Hasan, Yasmin; Chmura, Steven J.

    2012-01-01

    Purpose: To determine the feasibility of and acute toxicity associated with hypofractionated whole breast radiation (HypoRT) after breast-conserving surgery in patients excluded from or underrepresented in randomized trials comparing HypoRT with conventional fractionation schedules. Methods and Materials: A review was conducted of all patients consecutively treated with HypoRT at University of Chicago. All patients were treated to 42.56 Gy in 2.66 Gy daily fractions in either the prone or supine position. Planning was performed in most cases using wedges and large segments or a “field-in-field” technique. Breast volume was estimated using volumetric measurements of the planning target volume (PTV). Dosimetric parameters of heterogeneity (V105, V107, V110, and maximum dose) were recorded for each treatment plan. Acute toxicity was scored for each treated breast. Results: Between 2006 and 2010, 78 patients were treated to 80 breasts using HypoRT. Most women were overweight or obese (78.7%), with a median body mass index of 29.2 kg/m 2 . Median breast volume was 1,351 mL. Of the 80 treated breasts, the maximum acute skin toxicity was mild erythema or hyperpigmentation in 70.0% (56/80), dry desquamation in 21.25% (17/80), and focal moist desquamation in 8.75% (7/80). Maximum acute toxicity occurred after the completion of radiation in 31.9% of patients. Separation >25 cm was not associated with increased toxicity. Breast volume was the only patient factor significantly associated with moist desquamation on multivariable analysis (p = 0.01). Patients with breast volume >2,500 mL experienced focal moist desquamation in 27.2% of cases compared with 6.34% in patients with breast volume 25 cm and in patients with large breast volume when employing modern planning and positioning techniques. We recommend counseling regarding expected increases in skin toxicity in women with a PTV volume >2,500 mL.

  4. Feasibility and Acute Toxicity of Hypofractionated Radiation in Large-breasted Patients

    Energy Technology Data Exchange (ETDEWEB)

    Dorn, Paige L., E-mail: pdorn@radonc.uchicago.edu [Department of Radiation and Cellular Oncology, University of Chicago Hospitals, Chicago, IL (United States); Corbin, Kimberly S.; Al-Hallaq, Hania; Hasan, Yasmin; Chmura, Steven J. [Department of Radiation and Cellular Oncology, University of Chicago Hospitals, Chicago, IL (United States)

    2012-05-01

    Purpose: To determine the feasibility of and acute toxicity associated with hypofractionated whole breast radiation (HypoRT) after breast-conserving surgery in patients excluded from or underrepresented in randomized trials comparing HypoRT with conventional fractionation schedules. Methods and Materials: A review was conducted of all patients consecutively treated with HypoRT at University of Chicago. All patients were treated to 42.56 Gy in 2.66 Gy daily fractions in either the prone or supine position. Planning was performed in most cases using wedges and large segments or a 'field-in-field' technique. Breast volume was estimated using volumetric measurements of the planning target volume (PTV). Dosimetric parameters of heterogeneity (V105, V107, V110, and maximum dose) were recorded for each treatment plan. Acute toxicity was scored for each treated breast. Results: Between 2006 and 2010, 78 patients were treated to 80 breasts using HypoRT. Most women were overweight or obese (78.7%), with a median body mass index of 29.2 kg/m{sup 2}. Median breast volume was 1,351 mL. Of the 80 treated breasts, the maximum acute skin toxicity was mild erythema or hyperpigmentation in 70.0% (56/80), dry desquamation in 21.25% (17/80), and focal moist desquamation in 8.75% (7/80). Maximum acute toxicity occurred after the completion of radiation in 31.9% of patients. Separation >25 cm was not associated with increased toxicity. Breast volume was the only patient factor significantly associated with moist desquamation on multivariable analysis (p = 0.01). Patients with breast volume >2,500 mL experienced focal moist desquamation in 27.2% of cases compared with 6.34% in patients with breast volume <2,500 mL (p = 0.03). Conclusions: HypoRT is feasible and safe in patients with separation >25 cm and in patients with large breast volume when employing modern planning and positioning techniques. We recommend counseling regarding expected increases in skin toxicity in women

  5. A phase I/II study of hypofractionated whole abdominal radiation therapy in patients with chemoresistant ovarian carcinoma: Karnofsky score determines treatment outcome

    International Nuclear Information System (INIS)

    Faul, Clare; Gerszten, Kristina; Edwards, Robert; Land, Stephanie; D'Angelo, Gina M.S.; Kelley, Joseph; Price, Fredric

    2000-01-01

    Purpose: Radiation therapy can provide useful palliation in chemorefractory ovarian cancer patients. The purpose of this study was to prospectively study the palliative effect of a hypofractionated radiation treatment regimen. Change in quality-of-life scores (Functional Assessment of Cancer Therapy [FACT], Karnofsky scale), pain score, and tolerance to therapy were also assessed. Methods and Materials: A single-institution Phase I/II trial was initiated in patients with chemoresistant recurrent or progressive ovarian cancer. All patients had symptomatic and measurable intra-abdominal disease. Patients were treated with a single radiation fraction (700 cGy) or two fractions (300 cGy twice a day) to the whole abdomen over 1 day. Quality-of-life scale (FACT G version 2) was assessed at baseline and 1 and 3 months following treatment. Karnofsky scale and pain score were also evaluated in the same time frame. Results: Sixteen patients were prospectively entered into this protocol between February 1996 and September 1998. Twelve patients received a single 700 cGy fraction and four 300 cGy twice a day. All were heavily pretreated and 9 (56%) had a poor performance status prior to treatment. Symptoms needing palliation included pain (14), ascites (10), and bleeding (2). Symptomatic improvement occurred in all patients with pain (5 complete response [CR] and 7 partial response [PR], all patients with bleeding (CR 2), and two (20%) with ascites. Five patients (31%) had a reduction in lesion size documented radiologically in three. The mean duration of response was 22 weeks in patients with a Karnofsky score >70. Thirteen patients developed transient nausea and vomiting which resolved in 48 hours in all. All patients developed a transient lymphopenia. Thirteen patients completed a follow-up quality-of-life scale. There was an improvement in the physical and functional components of the scale in patients with Karnofsky score of 90-100. There was no improvement in quality of

  6. Transformation of Physical DVHs to Radiobiologically Equivalent Ones in Hypofractionated Radiotherapy Analyzing Dosimetric and Clinical Parameters: A Practical Approach for Routine Clinical Practice in Radiation Oncology

    Directory of Open Access Journals (Sweden)

    Zoi Thrapsanioti

    2013-01-01

    Full Text Available Purpose. The purpose of this study was to transform DVHs from physical to radiobiological ones as well as to evaluate their reliability by correlations of dosimetric and clinical parameters for 50 patients with prostate cancer and 50 patients with breast cancer, who were submitted to Hypofractionated Radiotherapy. Methods and Materials. To achieve this transformation, we used both the linear-quadratic model (LQ model and the Niemierko model. The outcome of radiobiological DVHs was correlated with acute toxicity score according to EORTC/RTOG criteria. Results. Concerning the prostate radiotherapy, there was a significant correlation between RTOG acute rectal toxicity and ( and ( dosimetric parameters, calculated for  Gy. Moreover, concerning the breast radiotherapy there was a significant correlation between RTOG skin toxicity and dosimetric parameter, calculated for both  Gy ( and  Gy (. The new tool seems reliable and user-friendly. Conclusions. Our proposed model seems user-friendly. Its reliability in terms of agreement with the presented acute radiation induced toxicity was satisfactory. However, more patients are needed to extract safe conclusions.

  7. A Pilot Study of Hypofractionated Stereotactic Radiation Therapy and Sunitinib in Previously Irradiated Patients With Recurrent High-Grade Glioma

    International Nuclear Information System (INIS)

    Wuthrick, Evan J.; Curran, Walter J.; Camphausen, Kevin; Lin, Alexander; Glass, Jon; Evans, James; Andrews, David W.; Axelrod, Rita; Shi, Wenyin; Werner-Wasik, Maria; Haacke, E. Mark; Hillman, Gilda G.; Dicker, Adam P.

    2014-01-01

    Purpose/Objective(s): Angiogenic blockade with irradiation may enhance the therapeutic ratio of radiation therapy (RT) through vascular normalization. We sought to determine the safety and toxicity profile of continuous daily-dosed sunitinib when combined with hypofractionated stereotactic RT (fSRT) for recurrent high-grade gliomas (rHGG). Methods and Materials: Eligible patients had malignant high-grade glioma that recurred or progressed after primary surgery and RT. All patients received a minimum of a 10-day course of fSRT, had World Health Organization performance status of 0 to 1, and a life expectancy of >3 months. During fSRT, sunitinib was administered at 37.5 mg daily. The primary endpoint was acute toxicity, and response was assessed via serial magnetic resonance imaging. Results: Eleven patients with rHGG were enrolled. The fSRT doses delivered ranged from 30 to 42 Gy in 2.5- to 3.75-Gy fractions. The median follow-up time was 40 months. Common acute toxicities included hematologic disorders, fatigue, hypertension, and elevated liver transaminases. Sunitinib and fSRT were well tolerated. One grade 4 mucositis toxicity occurred, and no grade 4 or 5 hypertensive events or intracerebral hemorrhages occurred. One patient had a nearly complete response, and 4 patients had stable disease for >9 months. Two patients (18%) remain alive and progression-free >3 years from enrollment. The 6-month progression-free survival was 45%. Conclusions: Sunitinib at a daily dose of 37.5 mg given concurrently with hypofractionated stereotactic reirradiation for rHGG yields acceptable toxicities and an encouraging 6-month progression-free survival

  8. A Pilot Study of Hypofractionated Stereotactic Radiation Therapy and Sunitinib in Previously Irradiated Patients With Recurrent High-Grade Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Wuthrick, Evan J., E-mail: evan.wuthrick@osumc.edu [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Curran, Walter J. [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Camphausen, Kevin [Department of Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland (United States); Lin, Alexander [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Glass, Jon; Evans, James; Andrews, David W. [Department of Neurological Surgery, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Axelrod, Rita [Department of Medical Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Shi, Wenyin; Werner-Wasik, Maria [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Haacke, E. Mark [Department of Radiology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan (United States); Department of Biomedical Engineering, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan (United States); Hillman, Gilda G. [Department of Radiation Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan (United States); Dicker, Adam P. [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2014-10-01

    Purpose/Objective(s): Angiogenic blockade with irradiation may enhance the therapeutic ratio of radiation therapy (RT) through vascular normalization. We sought to determine the safety and toxicity profile of continuous daily-dosed sunitinib when combined with hypofractionated stereotactic RT (fSRT) for recurrent high-grade gliomas (rHGG). Methods and Materials: Eligible patients had malignant high-grade glioma that recurred or progressed after primary surgery and RT. All patients received a minimum of a 10-day course of fSRT, had World Health Organization performance status of 0 to 1, and a life expectancy of >3 months. During fSRT, sunitinib was administered at 37.5 mg daily. The primary endpoint was acute toxicity, and response was assessed via serial magnetic resonance imaging. Results: Eleven patients with rHGG were enrolled. The fSRT doses delivered ranged from 30 to 42 Gy in 2.5- to 3.75-Gy fractions. The median follow-up time was 40 months. Common acute toxicities included hematologic disorders, fatigue, hypertension, and elevated liver transaminases. Sunitinib and fSRT were well tolerated. One grade 4 mucositis toxicity occurred, and no grade 4 or 5 hypertensive events or intracerebral hemorrhages occurred. One patient had a nearly complete response, and 4 patients had stable disease for >9 months. Two patients (18%) remain alive and progression-free >3 years from enrollment. The 6-month progression-free survival was 45%. Conclusions: Sunitinib at a daily dose of 37.5 mg given concurrently with hypofractionated stereotactic reirradiation for rHGG yields acceptable toxicities and an encouraging 6-month progression-free survival.

  9. Outcomes in Newly Diagnosed Elderly Glioblastoma Patients after Concomitant Temozolomide Administration and Hypofractionated Radiotherapy

    International Nuclear Information System (INIS)

    Nguyen, Ludovic T.; Touch, Socheat; Nehme-Schuster, Hélène; Antoni, Delphine; Eav, Sokha; Clavier, Jean-Baptiste; Bauer, Nicolas; Vigneron, Céline; Schott, Roland; Kehrli, Pierre; Noël, Georges

    2013-01-01

    This study aimed to analyze the treatment and outcomes of older glioblastoma patients. Forty-four patients older than 70 years of age were referred to the Paul Strauss Center for chemotherapy and radiotherapy. The median age was 75.5 years old (range: 70–84), and the patients included 18 females and 26 males. The median Karnofsky index (KI) was 70%. The Charlson indices varied from 4 to 6. All of the patients underwent surgery. O 6 -methylguanine–DNA methyltransferase (MGMT) methylation status was determined in 25 patients. All of the patients received radiation therapy. Thirty-eight patients adhered to a hypofractionated radiation therapy schedule and six patients to a normofractionated schedule. Neoadjuvant, concomitant and adjuvant chemotherapy regimens were administered to 12, 35 and 20 patients, respectively. At the time of this analysis, 41 patients had died. The median time to relapse was 6.7 months. Twenty-nine patients relapsed, and 10 patients received chemotherapy upon relapse. The median overall survival (OS) was 7.2 months and the one- and two-year OS rates were 32% and 12%, respectively. In a multivariate analysis, only the Karnofsky index was a prognostic factor. Hypofractionated radiotherapy and chemotherapy with temozolomide are feasible and acceptably tolerated in older patients. However, relevant prognostic factors are needed to optimize treatment proposals

  10. Hypofractionated radiotherapy for primary or secondary oligometastatic lung cancer using Tomotherapy

    International Nuclear Information System (INIS)

    Chang, Heng-Jui; Ko, Hui-Ling; Lee, Cheng-Yen; Wu, Ren-Hong; Yeh, Yu-Wung; Jiang, Jiunn-Song; Kao, Shang-Jyh; Chi, Kwan-Hwa

    2012-01-01

    To retrospectively review the outcome of patients with primary or secondary oligometastatic lung cancer, treated with hypofractionated Tomotherapy. Between April 2007 and June 2011, a total of 33 patients with oligometastatic intrapulmonary lesions underwent hypofractionated radiotherapy by Tomotherapy along with appropriate systemic therapy. There were 24 primary, and 9 secondary lung cancer cases. The radiation doses ranged from 4.5 to 7.0 Gy per fraction, multiplied by 8–16 fractions. The median dose per fraction was 4.5 Gy (range, 4.5-7.0 Gy), and the median total dose was 49.5 Gy (range, 45–72 Gy). The median estimated biological effective dose at 10 Gy (BED 10 ) was 71.8 Gy (range, 65.3–119.0 Gy), and that at 3 Gy (BED 3 ) was 123.8 Gy (range, 112.5–233.3 Gy). The mean lung dose (MLD) was constrained mainly under 1200 cGy. The median gross tumor volume (GTV) was 27.9 cm 3 (range: 2.5–178.1 cm 3 ). The median follow-up period was 25.8 months (range, 3.0–60.7 months). The median overall survival (OS) time was 32.1 months for the 24 primary lung cancer patients, and >40 months for the 9 metastatic lung patients. The median survival time of the patients with extra-pulmonary disease (EPD) was 11.2 months versus >50 months (not reached) in the patients without EPD (p < 0.001). Those patients with smaller GTV (≦27.9 cm 3 ) had a better survival than those with larger GTV (>27.9 cm 3 ): >40 months versus 12.85 months (p = 0.047). The patients with ≦2 lesions had a median survival >40 months, whereas those with ≧3 lesions had 26 months (p = 0.065). The 2-year local control (LC) rate was 94.7%. Only 2 patients (6.1%) developed ≧grade 3 radiation pneumonitis. Using Tomotherapy in hypofractionation may be effective for selected primary or secondary lung oligometastatic diseases, without causing significant toxicities. Pulmonary oligometastasis patients without EPD had better survival outcomes than those with EPD. Moreover, GTV is more significant than

  11. Hypofractionated radiotherapy for primary or secondary oligometastatic lung cancer using Tomotherapy

    Science.gov (United States)

    2012-01-01

    Background To retrospectively review the outcome of patients with primary or secondary oligometastatic lung cancer, treated with hypofractionated Tomotherapy. Methods Between April 2007 and June 2011, a total of 33 patients with oligometastatic intrapulmonary lesions underwent hypofractionated radiotherapy by Tomotherapy along with appropriate systemic therapy. There were 24 primary, and 9 secondary lung cancer cases. The radiation doses ranged from 4.5 to 7.0 Gy per fraction, multiplied by 8–16 fractions. The median dose per fraction was 4.5 Gy (range, 4.5-7.0 Gy), and the median total dose was 49.5 Gy (range, 45–72 Gy). The median estimated biological effective dose at 10 Gy (BED10) was 71.8 Gy (range, 65.3–119.0 Gy), and that at 3 Gy (BED3) was 123.8 Gy (range, 112.5–233.3 Gy). The mean lung dose (MLD) was constrained mainly under 1200 cGy. The median gross tumor volume (GTV) was 27.9 cm3 (range: 2.5–178.1 cm3). Results The median follow-up period was 25.8 months (range, 3.0–60.7 months). The median overall survival (OS) time was 32.1 months for the 24 primary lung cancer patients, and >40 months for the 9 metastatic lung patients. The median survival time of the patients with extra-pulmonary disease (EPD) was 11.2 months versus >50 months (not reached) in the patients without EPD (p 27.9 cm3): >40 months versus 12.85 months (p = 0.047). The patients with ≦2 lesions had a median survival >40 months, whereas those with ≧3 lesions had 26 months (p = 0.065). The 2-year local control (LC) rate was 94.7%. Only 2 patients (6.1%) developed ≧grade 3 radiation pneumonitis. Conclusion Using Tomotherapy in hypofractionation may be effective for selected primary or secondary lung oligometastatic diseases, without causing significant toxicities. Pulmonary oligometastasis patients without EPD had better survival outcomes than those with EPD. Moreover, GTV is more significant than lesion number in

  12. Clinical Usefulness of Implanted Fiducial Markers for Hypofractionated Radiotherapy of Prostate Cancer

    International Nuclear Information System (INIS)

    Choi, Young Min; Ahn, Sung Hwan; Lee, Hyung Hwan; Lee, Hyung Sik; Hur, Woo Joo; Yoon, Jin Han; Kim, Tae Hyo; Kim, Soo Dong; Yun, Seong Guk

    2011-01-01

    fractionations were 1.5% and 0% in the fiducial marker matching, respectively, and 49.3% and 17.9% in the pelvic bone matching, respectively. The more precise setup of hypofractionated radiotherapy for prostate cancer patients is feasible with the implanted fiducial marker matching compared with the pelvic bony matching. Therefore, a less marginal expansion of planning target volume produces less radiation exposure to adjacent normal tissues, which could ultimately make hypofractionated radiotherapy safer.

  13. Hypofractionated radiotherapy for Graves' orbitopathy

    International Nuclear Information System (INIS)

    Heyd, R.; Herkstroeter, M.; Martin, T.; Zamboglou, N.; Strassmann, G.

    2001-01-01

    Background: Radiotherapy (RT) has been proven effective in the management of Graves' orbitopathy in numerous studies. Most commonly is the use of conventional fractionated RT and the value of hypofractionated irradiation has not been investigated. Materials and methods: The results in 33 euthyroid cases who underwent RT with a total dose of 21.0 Gy given in three weekly fractions of 3.0 Gy are retrospectively analyzed. The duration of symptoms ranged from 1-84 months and all of the cases had treatment failure after previous administration of corticosteroids. After a mean follow-up period of 33.6 months the overall results were assessed according to the criteria by Donaldson et al. and for evaluation of the clinical outcome a classification with the main criteria being eye-lid changes, exophthalmos, myopathy and eye nerve involvement was used. Results: At follow-up, the overall response to RT was 84.8% (28/33 cases). The analysis with the clinical classification demonstrated that in 19/33 (57.6%) cases occurred a decrease of eye lid changes and exophthalmos and 12/33 (36.4%) had a relief of myopathy. 2/33 cases (6.0%) developed an eye nerve compression causing the necessity of surgical decompression. 3/33 cases (9.0%) had a progression of at least of one of the single criteria of the score and therefore they were classified as non-responders. Conclusions: Hypofractionated RT has been proven effective for treatment of severe cases of Graves' orbitopathy in cases with a prolongated duration of symptoms. The comparison with literature data demonstrate that the results after hypofractionated RT are comparable to those obtained after conventional fractionated RT. (orig.)

  14. Title: hypofractionated postoperative irradiation for cutaneous melanoma of the head and neck

    International Nuclear Information System (INIS)

    Omizo, Russ T.; Marquez, Carol M.; Vetto, John T.

    1996-01-01

    Purpose/Objective: To evaluate the efficacy and tolerance of hypofractionated postoperative irradiation in patients with head and neck cutaneous melanoma at high risk for local-regional recurrence. Methods and Materials: Between May 1990 to February 1995, 26 patients with cutaneous melanoma of the head and neck were evaluated in the Department of Radiation Oncology at the Oregon Health Sciences University for elective postoperative hypofractionated irradiation. Twelve patients were excluded from analysis because of simultaneous distant metastatic disease. The remaining 14 patients were at high risk for local-regional recurrence because of either nodal disease, T3 or greater disease, recurrent disease following previous treatment or a combination of the above. TNM stage distribution for patients treated at initial presentation was: T4aN1-2, T4aN0-3, T3bN0-1, T3aN0-1, T2N1-1 and TxN1-1. The initial TNM stage for patients presenting with recurrent disease was: T4aN2-a, T4aN1-1, T1N0-1, T2N0-1 and TxN1-1. All patients received adjuvant irradiation to at least 2 echelons of draining lymph nodes +/- the primary site. The median elapsed time between surgery and irradiation was 4 weeks. Hypofractionated irradiation consisted of 600 cGy fractions given twice weekly for 5 fractions. Twelve patients were treated with electrons of appropriate energy, 1 with photons and 1 with photons and electrons. Median duration of treatment was 15 days. Results: With a median follow-up of 41 months, 2 patients have failed local-regionally and at distant sites and one patient has failed with distant disease only. The actuarial 5 year local-regional control rate is 86% with a standard error of 9%. The actuarial 5 year survival is 60% with a standard error of 16%. Acute side effects were self limiting and were most commonly erythema and mucositis. Chronic side effects were mild and included fibrosis, telangiectasias and xerostomia. Conclusions: Adjuvant hypofractionated irradiation provides

  15. Outcomes in Newly Diagnosed Elderly Glioblastoma Patients after Concomitant Temozolomide Administration and Hypofractionated Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Ludovic T. [Neurology Department, CHU Hautepierre, rue Molière, Strasbourg 67000 (France); Touch, Socheat [Radiation Oncology University Department, Paul Strauss Center, 3, rue de la Porte de l’Hôpital, BP 42, Strasbourg cedex 67065 (France); Radiation Oncology Department, Soviet-Khmer Friendship Hospital, Pnom-Pehn 12400 (Cambodia); Nehme-Schuster, Hélène [Oncology Geriatric Department, Paul Strauss Center, 3, rue de la Porte de l’Hôpital, BP 42, Strasbourg cedex 67065 (France); Antoni, Delphine [Radiation Oncology University Department, Paul Strauss Center, 3, rue de la Porte de l’Hôpital, BP 42, Strasbourg cedex 67065 (France); Eav, Sokha [Radiation Oncology Department, Soviet-Khmer Friendship Hospital, Pnom-Pehn 12400 (Cambodia); Clavier, Jean-Baptiste; Bauer, Nicolas; Vigneron, Céline [Radiation Oncology University Department, Paul Strauss Center, 3, rue de la Porte de l’Hôpital, BP 42, Strasbourg cedex 67065 (France); Schott, Roland [Oncology Department, Paul Strauss Center, 3, rue de la Porte de l’Hôpital, BP 42, Strasbourg cedex 67065 (France); Kehrli, Pierre [Neurosurgery Department, CHU Hautepierre, rue Molière, Strasbourg 67000 (France); Noël, Georges, E-mail: gnoel@strasbourg.unicancer.fr [Radiation Oncology University Department, Paul Strauss Center, 3, rue de la Porte de l’Hôpital, BP 42, Strasbourg cedex 67065 (France); Laboratoire EA 3430, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg 67000 (France)

    2013-09-24

    This study aimed to analyze the treatment and outcomes of older glioblastoma patients. Forty-four patients older than 70 years of age were referred to the Paul Strauss Center for chemotherapy and radiotherapy. The median age was 75.5 years old (range: 70–84), and the patients included 18 females and 26 males. The median Karnofsky index (KI) was 70%. The Charlson indices varied from 4 to 6. All of the patients underwent surgery. O{sub 6}-methylguanine–DNA methyltransferase (MGMT) methylation status was determined in 25 patients. All of the patients received radiation therapy. Thirty-eight patients adhered to a hypofractionated radiation therapy schedule and six patients to a normofractionated schedule. Neoadjuvant, concomitant and adjuvant chemotherapy regimens were administered to 12, 35 and 20 patients, respectively. At the time of this analysis, 41 patients had died. The median time to relapse was 6.7 months. Twenty-nine patients relapsed, and 10 patients received chemotherapy upon relapse. The median overall survival (OS) was 7.2 months and the one- and two-year OS rates were 32% and 12%, respectively. In a multivariate analysis, only the Karnofsky index was a prognostic factor. Hypofractionated radiotherapy and chemotherapy with temozolomide are feasible and acceptably tolerated in older patients. However, relevant prognostic factors are needed to optimize treatment proposals.

  16. Outcomes and toxicity from a prospective study of moderately hypofractionated radiation therapy for prostate cancer

    Directory of Open Access Journals (Sweden)

    Wei Gang Wang, MD

    2018-04-01

    Full Text Available Purpose: The purpose of this study is to report the long-term outcomes and toxicity results of a prospective trial of moderately hypofractionated, image guided radiation therapy (RT for localized prostate cancer. Methods and materials: Patients were enrolled between December 2006 and February 2012. Patients in group 1 were stage T1-T2b, had a Gleason score (GS of 2 to 6 or 7 (3 + 4 with only 1 lobe involved, and had prostate-specific antigen levels ≤10 ng/mL. Group 2 patients were stage ≥T2c, had a GS ≥7 (4 + 3, a GS 7 (3 + 4 involving both lobes, or a PSA >10 ng/mL and ≤30 ng/mL. All patients underwent transrectal ultrasound guided fiducial (Visicoil placement prior to computed tomography/magnetic resonance imaging simulation. Daily cone beam computed tomography with online correction was used. The prescribed dose was 64 Gy in 20 fractions. The primary endpoint was acute and late toxicity. The secondary endpoint was biochemical control. Results: A total of 40 patients with a median age of 70 years were recruited for the study. Twenty-two patients (55% were in group 1, and 18 patients (45% were in group 2. Thirteen patients (32.5% were classified as low, 26 patients (65% as intermediate, and 1 patient (2.5% as high risk per the National Comprehensive Cancer Network criteria. The median follow-up time was 59 months. Five-year biochemical control was 100% and 94.4% for groups 1 and 2, respectively. Thirteen patients (32.5% developed acute gastrointestinal (GI toxicities grade ≥2 and 3 (7.5% developed acute grade 3 GI toxicity. A total of 17 patients (42.5% developed grade ≥2 acute genitourinary toxicities and 1 (2.5% developed acute grade 3 dysuria. Two patients (5% developed late GI toxicities grade ≥2. There was 1 case (2.5% of grade 4 fistula requiring sigmoid resection. Seven patients (17.5% developed grade ≥2 late genitourinary toxicities; 2 patients (5% late grade 3 urinary frequency/urgency. Conclusions

  17. Hypofractionated stereotactic body radiation therapy for elderly patients with stage IIB–IV nonsmall cell lung cancer who are ineligible for or refuse other treatment modalities

    Directory of Open Access Journals (Sweden)

    Karam SD

    2014-10-01

    Full Text Available Sana D Karam,1 Zachary D Horne,2 Robert L Hong,2 Don McRae,2 David Duhamel,3 Nadim M Nasr2 1Department of Radiation Oncology, University of Colorado, Denver, CO, USA; 2Department of Radiation Oncology, 3Department of Pulmonary/Critical Care Medicine, Virginia Hospital Center, Arlington, VA, USA Objective: In elderly patients with stage IIB–IV nonsmall cell lung cancer who cannot tolerate chemotherapy, conventionally fractionated radiotherapy is the treatment of choice. We present our experience with hypofractionated stereotactic body radiation therapy (SBRT in the treatment of this patient population. Methods: Thirty-three patients with a median age of 80 years treated with fractionated SBRT were retrospectively analyzed. Most patients were smokers and had preexisting lung disease and either refused treatment or were ineligible. A median prescribed dose of 40 Gy was delivered to the prescription isodose line over a median of five treatments. The majority of patients (70% did not receive chemotherapy. Results: With a median follow-up of 9 months (range: 4–40 months, the actuarial median overall survival (OS and progression-free survival were 12 months for both. One year actuarial survival outcomes were 75%, 58%, 44%, and 48% for local control, regional control, progression-free survival, and OS, respectively. Increased volume of disease was a statistically significant predictor of worse OS. Three patients developed a grade 1 cough that peaked 3 weeks after treatment and resolved within 1 month. One patient developed grade 1 tracheal mucositis and three patients developed grade 1 pneumonitis. Both resolved 6 weeks after treatment. Three patients died within the first month of treatment, but the cause of death did not appear to be related to the treatment. Conclusion: Hypofractionated SBRT is a relatively safe and convenient treatment option for elderly patients with inoperable stage IIB–IV nonsmall cell lung cancer. However, given the small

  18. Hypofractionated radiotherapy for primary or secondary oligometastatic lung cancer using Tomotherapy

    Directory of Open Access Journals (Sweden)

    Chang Heng-Jui

    2012-12-01

    Full Text Available Abstract Background To retrospectively review the outcome of patients with primary or secondary oligometastatic lung cancer, treated with hypofractionated Tomotherapy. Methods Between April 2007 and June 2011, a total of 33 patients with oligometastatic intrapulmonary lesions underwent hypofractionated radiotherapy by Tomotherapy along with appropriate systemic therapy. There were 24 primary, and 9 secondary lung cancer cases. The radiation doses ranged from 4.5 to 7.0 Gy per fraction, multiplied by 8–16 fractions. The median dose per fraction was 4.5 Gy (range, 4.5-7.0 Gy, and the median total dose was 49.5 Gy (range, 45–72 Gy. The median estimated biological effective dose at 10 Gy (BED10 was 71.8 Gy (range, 65.3–119.0 Gy, and that at 3 Gy (BED3 was 123.8 Gy (range, 112.5–233.3 Gy. The mean lung dose (MLD was constrained mainly under 1200 cGy. The median gross tumor volume (GTV was 27.9 cm3 (range: 2.5–178.1 cm3. Results The median follow-up period was 25.8 months (range, 3.0–60.7 months. The median overall survival (OS time was 32.1 months for the 24 primary lung cancer patients, and >40 months for the 9 metastatic lung patients. The median survival time of the patients with extra-pulmonary disease (EPD was 11.2 months versus >50 months (not reached in the patients without EPD (p 3 had a better survival than those with larger GTV (>27.9 cm3: >40 months versus 12.85 months (p = 0.047. The patients with ≦2 lesions had a median survival >40 months, whereas those with ≧3 lesions had 26 months (p = 0.065. The 2-year local control (LC rate was 94.7%. Only 2 patients (6.1% developed ≧grade 3 radiation pneumonitis. Conclusion Using Tomotherapy in hypofractionation may be effective for selected primary or secondary lung oligometastatic diseases, without causing significant toxicities. Pulmonary oligometastasis patients without EPD had better survival outcomes than those with

  19. Hypo-fractionated whole breast irradiation: Pro and cons; Irradiation hypofractionnee dans le cancer du sein: pour ou contre?

    Energy Technology Data Exchange (ETDEWEB)

    Cutuli, B. [Institut du cancer Courlancy, 38, rue de Courlancy, 51100 Reims (France); Fourquet, A. [Institut Curie, 26, rue d' Ulm, 75005 Paris (France)

    2011-10-15

    The continuous increase of breast cancer (BC) incidence, the logistic constraints of the protracted standard 5-week radiations regimen have led to test short hypo-fractionated whole breast radiation therapy schemes. Three prospective randomized trials and a pilot trial have been published. Large numbers of patients were included, with follow-up duration ranging from 5 to 12 years. The conclusions of these trials were similar, showing local control and toxicity equivalent to those of the standard regimen, and supporting the use of three schemes: 42.5 Gy/16 fractions/3 weeks, 40 Gy/15 fractions/3 weeks or 41.6 Gy/13 fractions/5 weeks. However, the patients in these trials had favourable prognostic factors, were treated to the breast only and the boost dose, when indicated, was delivered with a standard fractionation. Hypo-fractionated treatment can only be recommended in patients treated to the breast only, without nodal involvement, with grade < 3 tumours and who are not candidate to chemotherapy. If a boost is to be given, a standard fractionation should be used. Particular care should be taken to avoid heterogeneities leading to high fractional doses to organs at risk (lung and heart). (authors)

  20. SU-E-T-776: Use of Quality Metrics for a New Hypo-Fractionated Pre-Surgical Mesothelioma Protocol

    International Nuclear Information System (INIS)

    Richardson, S; Mehta, V

    2015-01-01

    Purpose: The “SMART” (Surgery for Mesothelioma After Radiation Therapy) approach involves hypo-fractionated radiotherapy of the lung pleura to 25Gy over 5 days followed by surgical resection within 7. Early clinical results suggest that this approach is very promising, but also logistically challenging due to the multidisciplinary involvement. Due to the compressed schedule, high dose, and shortened planning time, the delivery of the planned doses were monitored for safety with quality metric software. Methods: Hypo-fractionated IMRT treatment plans were developed for all patients and exported to Quality Reports™ software. Plan quality metrics or PQMs™ were created to calculate an objective scoring function for each plan. This allows for an objective assessment of the quality of the plan and a benchmark for plan improvement for subsequent patients. The priorities of various components were incorporated based on similar hypo-fractionated protocols such as lung SBRT treatments. Results: Five patients have been treated at our institution using this approach. The plans were developed, QA performed, and ready within 5 days of simulation. Plan Quality metrics utilized in scoring included doses to OAR and target coverage. All patients tolerated treatment well and proceeded to surgery as scheduled. Reported toxicity included grade 1 nausea (n=1), grade 1 esophagitis (n=1), grade 2 fatigue (n=3). One patient had recurrent fluid accumulation following surgery. No patients experienced any pulmonary toxicity prior to surgery. Conclusion: An accelerated course of pre-operative high dose radiation for mesothelioma is an innovative and promising new protocol. Without historical data, one must proceed cautiously and monitor the data carefully. The development of quality metrics and scoring functions for these treatments allows us to benchmark our plans and monitor improvement. If subsequent toxicities occur, these will be easy to investigate and incorporate into the

  1. SU-E-T-776: Use of Quality Metrics for a New Hypo-Fractionated Pre-Surgical Mesothelioma Protocol

    Energy Technology Data Exchange (ETDEWEB)

    Richardson, S; Mehta, V [Swedish Cancer Institute, Seattle, WA (United States)

    2015-06-15

    Purpose: The “SMART” (Surgery for Mesothelioma After Radiation Therapy) approach involves hypo-fractionated radiotherapy of the lung pleura to 25Gy over 5 days followed by surgical resection within 7. Early clinical results suggest that this approach is very promising, but also logistically challenging due to the multidisciplinary involvement. Due to the compressed schedule, high dose, and shortened planning time, the delivery of the planned doses were monitored for safety with quality metric software. Methods: Hypo-fractionated IMRT treatment plans were developed for all patients and exported to Quality Reports™ software. Plan quality metrics or PQMs™ were created to calculate an objective scoring function for each plan. This allows for an objective assessment of the quality of the plan and a benchmark for plan improvement for subsequent patients. The priorities of various components were incorporated based on similar hypo-fractionated protocols such as lung SBRT treatments. Results: Five patients have been treated at our institution using this approach. The plans were developed, QA performed, and ready within 5 days of simulation. Plan Quality metrics utilized in scoring included doses to OAR and target coverage. All patients tolerated treatment well and proceeded to surgery as scheduled. Reported toxicity included grade 1 nausea (n=1), grade 1 esophagitis (n=1), grade 2 fatigue (n=3). One patient had recurrent fluid accumulation following surgery. No patients experienced any pulmonary toxicity prior to surgery. Conclusion: An accelerated course of pre-operative high dose radiation for mesothelioma is an innovative and promising new protocol. Without historical data, one must proceed cautiously and monitor the data carefully. The development of quality metrics and scoring functions for these treatments allows us to benchmark our plans and monitor improvement. If subsequent toxicities occur, these will be easy to investigate and incorporate into the

  2. Acute genitourinary toxicity after high-dose-rate (HDR) brachytherapy combined with hypofractionated external-beam radiation therapy for localized prostate cancer: Correlation between the urethral dose in HDR brachytherapy and the severity of acute genitourinary toxicity

    International Nuclear Information System (INIS)

    Akimoto, Tetsuo; Ito, Kazuto; Saitoh, Jun-ichi; Noda, Shin-ei; Harashima, Koichi; Sakurai, Hideyuki; Nakayama, Yuko; Yamamoto, Takumi; Suzuki, Kazuhiro; Nakano, Takashi; Niibe, Hideo

    2005-01-01

    Purpose: Several investigations have revealed that the α/β ratio for prostate cancer is atypically low, and that hypofractionation or high-dose-rate (HDR) brachytherapy regimens using appropriate radiation doses may be expected to yield tumor control and late sequelae rates that are better or at least as favorable as those achieved with conventional radiation therapy. In this setting, we attempted treating localized prostate cancer patients with HDR brachytherapy combined with hypofractionated external beam radiation therapy (EBRT). The purpose of this study was to evaluate the feasibility of using this approach, with special emphasis on the relationship between the severity of acute genitourinary (GU) toxicity and the urethral dose calculated from the dose-volume histogram (DVH) of HDR brachytherapy. Methods and Materials: Between September 2000 and December 2003, 70 patients with localized prostate cancer were treated by iridium-192 HDR brachytherapy combined with hypofractionated EBRT at the Gunma University Hospital. Hypofractionated EBRT was administered in fraction doses of 3 Gy, three times per week; a total dose of 51 Gy was delivered to the prostate gland and the seminal vesicles using the four-field technique. No elective pelvic irradiation was performed. After the completion of EBRT, all the patients additionally received transrectal ultrasonography (TRUS)-guided HDR brachytherapy. The fraction size and the number of fractions in HDR brachytherapy were prospectively changed, whereas the total radiation dose for EBRT was fixed at 51 Gy. The fractionation in HDR brachytherapy was as follows: 5 Gy x 5, 7 Gy x 3, 9 Gy x 2, administered twice per day, although the biologic effective dose (BED) for HDR brachytherapy combined with EBRT, assuming that the α/β ratio is 3, was almost equal to 138 in each fractionation group. The planning target volume was defined as the prostate gland with 5-mm margin all around, and the planning was conducted based on

  3. Postoperative Radiation Therapy for Prostate Cancer: Comparison of Conventional Versus Hypofractionated Radiation Regimens.

    Science.gov (United States)

    Tandberg, Daniel J; Oyekunle, Taofik; Lee, W Robert; Wu, Yuan; Salama, Joseph K; Koontz, Bridget F

    2018-06-01

    To compare acute/late toxicity and biochemical control in contemporaneous prostate cancer patient cohorts treated with hypofractionated postprostatectomy radiation therapy (hypoPORT) or conventional PORT (coPORT). Consecutive patients treated with intensity modulated hypoPORT (2.5 Gy per fraction, median cumulative dose 65 Gy [range, 57.5-70 Gy]) or coPORT (1.8-2.0 Gy per fraction, median cumulative dose 66 Gy [range, 60-74 Gy]) between 2005 and 2016 at 2 institutions constituted the study cohort. Acute toxicity and cumulative late grade 2 and ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity incidences were calculated for all patients using the Kaplan-Meier method and compared between cohorts. Biochemical progression-free survival (bPFS) was calculated in patients with ≥12 months' follow-up. Median follow-up for all 461 patients was 38.6 months. Of the 461 patients, 167 (36%) received hypoPORT, and 294 (64%) patients received coPORT. The hypoPORT cohort had significantly worse baseline urinary incontinence. Acute grade ≥2 GU toxicity was more common after hypoPORT (22% vs 8%) (P = .0001). Late grade ≥3 GU toxicity cumulative incidence at 6 years was 11% (hypoPORT) and 4% (coPORT) (P = .0081). However, hypoPORT was not associated with late grade ≥2 GU toxicity on multivariate analysis (hazard ratio 1.39, 95% confidence interval 0.86-2.34) (P = .18). There was no difference in acute or late GI toxicity. In the subset of patients with ≥12 month's follow-up (n = 364, median follow-up 52 months), 4-year bPFS was 78% (95% CI 69.4-85.0) after hypoPORT (P = .0038) and 65% (95% CI 57.6-71.1) after coPORT. HypoPORT was not significant for bPFS on multivariate analysis (hazard ratio 0.64, 95% CI 0.41-1.02, P = .059). HypoPORT shows promising early biochemical control. After controlling for baseline urinary function, hypoPORT was not associated with greater GU toxicity than coPORT. © 2018 Elsevier Inc. Copyright © 2018 Elsevier Inc. All

  4. Reproducibility and geometric accuracy of the fixster system during hypofractionated stereotactic radiotherapy

    International Nuclear Information System (INIS)

    Lindvall, Peter; Bergström, Per; Löfroth, Per-Olov; Henriksson, Roger; Bergenheim, A Tommy

    2008-01-01

    Hypofractionated radiotherapy has been used for the treatment of AVMs and brain metastases. Hypofractionation necessitates the use of a relocatable stereotactic frame that has to be applied on several occasions. The stereotactic frame needs to have a high degree of reproducibility, and patient positioning is crucial to achieve a high accuracy of the treatment. In this study we have, by radiological means, evaluated the reproducibility of the isocenter in consecutive treatment sessions using the Fixster frame. Deviations in the X, Y and Z-axis were measured in 10 patients treated with hypofractionated radiotherapy. The mean deviation in the X-axis was 0.4 mm (range -2.1 – 2.1, median 0.7 mm) and in the Y-axis -0.3 mm (range -1.4 – 0.7, median -0.2 mm). The mean deviation in the Z-axis was -0.6 (range -1.4 – 1.4, median 0.0 mm). There is a high degree of reproducibility of the isocenter during successive treatment sessions with HCSRT using the Fixster frame for stereotactic targeting. The high reducibility enables a safe treatment using hypofractionated stereotactic radiotherapy

  5. Macroscopic Hematuria After Conventional or Hypofractionated Radiation Therapy: Results From a Prospective Phase 3 Study

    Energy Technology Data Exchange (ETDEWEB)

    Sanguineti, Giuseppe, E-mail: sanguineti@ifo.it [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy); Arcidiacono, Fabio [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy); Landoni, Valeria [Department of Physics, Regina Elena National Cancer Institute, Rome (Italy); Saracino, Bianca Maria; Farneti, Alessia; Arcangeli, Stefano; Petrongari, Maria Grazia; Gomellini, Sara [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy); Strigari, Lidia [Department of Physics, Regina Elena National Cancer Institute, Rome (Italy); Arcangeli, Giorgio [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy)

    2016-10-01

    Purpose: To assess the macroscopic hematuria rates within a single-institution randomized phase 3 trial comparing dose-escalated, conventionally fractionated radiation therapy (CFRT) and moderately hypofractionated radiation therapy (MHRT) for localized prostate cancer. Methods and Materials: Patients with intermediate- to high-risk localized prostate cancer were treated with conformal RT and short-course androgen deprivation. Both the prostate and the entire seminal vesicles were treated to 80 Gy in 40 fractions over 8 weeks (CFRT) or 62 Gy in 20 fractions over 5 weeks (MHRT). The endpoint of the present study was the development of any episode or grade of macroscopic hematuria. The median follow-up period was 93 months (range 6-143). Results: Macroscopic hematuria was reported by 25 of 168 patients (14.9%). The actuarial estimate of hematuria at 8 years was 17.0% (95% confidence interval [CI] 10.7%-23.3%). The number of patients with hematuria was 6 and 19 in the CFRT and MHRT arms, respectively, for an actuarial 8-year estimate of 9.7% and 24.3%, respectively (hazard ratio 3.468, 95% CI 1.385-8.684; P=.008). Overall, 8 of 25 patients were found to have biopsy-proven urothelial carcinoma (3 in the CFRT arm and 5 in the MHRT arm; P=.27). Thus, the 8-year actuarial incidence of macroscopic hematuria (after censoring urothelial cancer–related episodes) was 4.1% and 18.2% after CFRT and MHRT, respectively (hazard ratio 4.961, 95% CI 1.426-17.263; P=.012). The results were confirmed by multivariate analysis after accounting for several patient-, treatment-, and tumor-related covariates. Conclusions: MHRT was associated with a statistically significant increased risk of macroscopic hematuria compared with CFRT.

  6. Macroscopic Hematuria After Conventional or Hypofractionated Radiation Therapy: Results From a Prospective Phase 3 Study

    International Nuclear Information System (INIS)

    Sanguineti, Giuseppe; Arcidiacono, Fabio; Landoni, Valeria; Saracino, Bianca Maria; Farneti, Alessia; Arcangeli, Stefano; Petrongari, Maria Grazia; Gomellini, Sara; Strigari, Lidia; Arcangeli, Giorgio

    2016-01-01

    Purpose: To assess the macroscopic hematuria rates within a single-institution randomized phase 3 trial comparing dose-escalated, conventionally fractionated radiation therapy (CFRT) and moderately hypofractionated radiation therapy (MHRT) for localized prostate cancer. Methods and Materials: Patients with intermediate- to high-risk localized prostate cancer were treated with conformal RT and short-course androgen deprivation. Both the prostate and the entire seminal vesicles were treated to 80 Gy in 40 fractions over 8 weeks (CFRT) or 62 Gy in 20 fractions over 5 weeks (MHRT). The endpoint of the present study was the development of any episode or grade of macroscopic hematuria. The median follow-up period was 93 months (range 6-143). Results: Macroscopic hematuria was reported by 25 of 168 patients (14.9%). The actuarial estimate of hematuria at 8 years was 17.0% (95% confidence interval [CI] 10.7%-23.3%). The number of patients with hematuria was 6 and 19 in the CFRT and MHRT arms, respectively, for an actuarial 8-year estimate of 9.7% and 24.3%, respectively (hazard ratio 3.468, 95% CI 1.385-8.684; P=.008). Overall, 8 of 25 patients were found to have biopsy-proven urothelial carcinoma (3 in the CFRT arm and 5 in the MHRT arm; P=.27). Thus, the 8-year actuarial incidence of macroscopic hematuria (after censoring urothelial cancer–related episodes) was 4.1% and 18.2% after CFRT and MHRT, respectively (hazard ratio 4.961, 95% CI 1.426-17.263; P=.012). The results were confirmed by multivariate analysis after accounting for several patient-, treatment-, and tumor-related covariates. Conclusions: MHRT was associated with a statistically significant increased risk of macroscopic hematuria compared with CFRT.

  7. Hypofractionated stereotactic radiotherapy of acoustic neuroma. Volume changes and hearing results after 89-month median follow-up

    International Nuclear Information System (INIS)

    Kranzinger, Manfred; Fastner, Gerd; Zehentmayr, Franz; Sedlmayer, Felix; Oberascher, Gerhard; Merz, Florian; Rahim, Hassan; Nairz, Olaf

    2014-01-01

    The goal of this work was to evaluate toxicity and local control following hypofractionated stereotactic radiation treatment with special focus on changes in tumor volume and hearing capacity. In all, 29 patients with unilateral acoustic neuroma were treated between 2001 and 2007 within a prospective radiation protocol (7 x 4 Gy ICRU dose). Median tumor volume was 0.9 ml. Follow-up started at 6 months and was repeated annually with MRI volumetry and audiometry. Hearing preservation was defined as preservation of Class A/B hearing according to the guidelines of the American Academy of Otolaryngology (1995). No patient had any intervention after a median imaging follow-up of 89.5 months, one patient showed radiological progression. Transient increase of tumor volume developed in 17/29 patients, whereas 22/29 patients (75.9 %) presented with a volume reduction at last follow-up. A total of 21 patients were eligible for hearing evaluation. Mean pure tone average (PTA) deteriorated from 39.3 to 65.9 dB and mean speech discrimination score (SDS) dropped from 74.3 to 38.1 %. The 5-year actuarial Class A/B hearing preservation rate was 50.0 ± 14.4 %. Radiation increases only minimally, if at all, the hearing deterioration which emerges by observation alone. Presbyacusis is not responsible for this deterioration. Transient tumor enlargement is common. Today radiation of small- and medium-sized acoustic neuroma can be performed with different highly conformal techniques as fractionated treatment or single low-dose radiosurgery with equal results regarding tumor control, hearing preservation, and side effects. Hypofractionation is more comfortable for the patient than conventional regimens and represents a serious alternative to frameless radiosurgery. (orig.) [de

  8. SU-G-JeP4-09: Impact of Interfractional Motion On Hypofractionated Pencil Beam Scanning Proton Therapy for Prostate Cancer

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    Moteabbed, M; Trofimov, A; Sharp, G; Wang, Y; Zietman, A; Efstathiou, J; Lu, H [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States)

    2016-06-15

    . Conclusion: Hypofractionation makes proton therapy of prostate more susceptible to interfractional motion-induced target dose degradation compared to the standard fractionation.

  9. Concurrent Boost with Adjuvant Breast Hypofractionated Radiotherapy and Toxicity Assessment

    Directory of Open Access Journals (Sweden)

    Mona M. Sayed

    2015-01-01

    Full Text Available Background: The use of shorter radiotherapy schedules has an economic and logistic advantage for radiotherapy departments, as well as a high degree of patient convenience. The aim of this study is to assess the acute and short-term late toxicities of a hypofractionated radiotherapy schedule with a concomitant boost. Methods: We enrolled 57 eligible patients as group A. These patients received 42.5 Gy in 16 fractions of 2.66 Gy each to the whole breast over 3.2 weeks. A concomitant electron boost of 12 Gy in 16 fractions was also administered which gave an additional 0.75 Gy daily to the lumpectomy area for a total radiation dose of 54.5 Gy. Toxicity was recorded at three weeks and at three months for this group as well as for a control group (group B. The control group comprised 76 eligible patients treated conventionally with 50 Gy to the whole breast over five weeks followed by a sequential electron boost of 12 Gy in 2 Gy per fraction. Results: There were no statistically significant differences observed in the incidence of acute skin toxicity, breast pain, and edema recorded at three weeks or pigmentation and fibrosis recorded at three months between the two groups (P0.05. Conclusion: The results of this study suggest there are no increased acute and shortterm late toxicities affiliated with the hypofractionated schedule plus a concomitant boost as prescribed compared to the conventional fractionation of adjuvant breast radiotherapy. Large randomized trials and long-term follow-up are needed to confirm these favorable findings.

  10. Acute genitourinary toxicity after high dose rate (HDR) brachytherapy combined with hypofractionated external-beam radiation therapy for localized prostate cancer: Second analysis to determine the correlation between the urethral dose in HDR brachytherapy and the severity of acute genitourinary toxicity

    International Nuclear Information System (INIS)

    Akimoto, Tetsuo; Katoh, Hiroyuki; Noda, Shin-ei; Ito, Kazuto; Yamamoto, Takumi; Kashiwagi, Bunzo; Nakano, Takashi

    2005-01-01

    Purpose: We have been treating localized prostate cancer with high-dose-rate (HDR) brachytherapy combined with hypofractionated external beam radiation therapy (EBRT) at our institution. We recently reported the existence of a correlation between the severity of acute genitourinary (GU) toxicity and the urethral radiation dose in HDR brachytherapy by using different fractionation schema. The purpose of this study was to evaluate the role of the urethral dose in the development of acute GU toxicity more closely than in previous studies. For this purpose, we conducted an analysis of patients who had undergone HDR brachytherapy with a fixed fractionation schema combined with hypofractionated EBRT. Methods and Materials: Among the patients with localized prostate cancer who were treated by 192-iridium HDR brachytherapy combined with hypofractionated EBRT at Gunma University Hospital between August 2000 and November 2004, we analyzed 67 patients who were treated by HDR brachytherapy with the fractionation schema of 9 Gy x two times combined with hypofractionated EBRT. Hypofractionated EBRT was administered at a fraction dose of 3 Gy three times weekly, and a total dose of 51 Gy was delivered to the prostate gland and seminal vesicles using the four-field technique. No elective pelvic irradiation was performed. After the completion of EBRT, all the patients additionally received transrectal ultrasonography-guided HDR brachytherapy. The planning target volume was defined as the prostate gland with a 5-mm margin all around, and the planning was conducted based on computed tomography images. The tumor stage was T1c in 13 patients, T2 in 31 patients, and T3 in 23 patients. The Gleason score was 2-6 in 12 patients, 7 in 34 patients, and 8-10 in 21 patients. Androgen ablation was performed in all the patients. The median follow-up duration was 11 months (range 3-24 months). The toxicities were graded based on the Radiation Therapy Oncology Group and the European Organization

  11. Helical tomotherapy for SIB and hypo-fractionated treatments in lung carcinomas: A 4D Monte Carlo treatment planning study

    International Nuclear Information System (INIS)

    Sterpin, Edmond; Janssens, Guillaume; Orban de Xivry, Jonathan; Goossens, Samuel; Wanet, Marie; Lee, John A.; Delor, Antoine; Bol, Vanesa; Vynckier, Stefaan; Gregoire, Vincent; Geets, Xavier

    2012-01-01

    Purpose: To evaluate the impact of intra-fraction motion induced by regular breathing on treatment quality for helical tomotherapy treatments. Material and methods: Four patients treated by simultaneous-integrated boost (SIB) and three by hypo-fractionated stereotactic treatments (hypo-fractionated, 18 Gy/fraction) were included. All patients were coached to ensure regular breathing. For the SIB group, the tumor volume was delineated using CT information only (CTV CT ) and the boost region was based on PET information (GTV PET , no CTV extension). In the hypo-fractionated group, a GTV based on CT information was contoured. In both groups, ITVs were defined according to 4D data. The PTV included the ITV plus a setup error margin. The treatment was planned using the tomotherapy TPS on 3D CT images. In order to verify the impact of intra-fraction motion and interplay effects, dose calculations were performed using a previously validated Monte Carlo model of tomotherapy (TomoPen): first on the planning 3D CT (“planned dose”) and second, on the 10 phases of the 4D scan. For the latter, two dose distributions, termed “interplay simulated” or “no interplay” were computed with and without beamlet-phase correlation over the 10 phases and combined using deformable dose registration. Results: In all cases, DVHs of “interplay simulated” dose distributions complied within 1% of the original clinical objectives used for planning, defined according to ICRU (report 83) and RTOG (trials 0236 and 0618) recommendations, for SIB and hypo-fractionated groups, respectively. For one patient in the hypo-fractionated group, D mean to the CTV CT was 2.6% and 2.5% higher than “planned” for “interplay simulated” and “no interplay”, respectively. Conclusion: For the patients included in this study, assuming regular breathing, the results showed that interplay of breathing and tomotherapy delivery motions did not affect significantly plan delivery accuracy. Hence

  12. Adjuvant Hypofractionated Versus Conventional Whole Breast Radiation Therapy for Early-Stage Breast Cancer: Long-Term Hospital-Related Morbidity From Cardiac Causes

    International Nuclear Information System (INIS)

    Chan, Elisa K.; Woods, Ryan; McBride, Mary L.; Virani, Sean; Nichol, Alan; Speers, Caroline; Wai, Elaine S.; Tyldesley, Scott

    2014-01-01

    Purpose: The risk of cardiac injury with hypofractionated whole-breast/chest wall radiation therapy (HF-WBI) compared with conventional whole-breast/chest wall radiation therapy (CF-WBI) in women with left-sided breast cancer remains a concern. The purpose of this study was to determine if there is an increase in hospital-related morbidity from cardiac causes with HF-WBI relative to CF-WBI. Methods and Materials: Between 1990 and 1998, 5334 women ≤80 years of age with early-stage breast cancer were treated with postoperative radiation therapy to the breast or chest wall alone. A population-based database recorded baseline patient, tumor, and treatment factors. Hospital administrative records identified baseline cardiac risk factors and other comorbidities. Factors between radiation therapy groups were balanced using a propensity-score model. The first event of a hospital admission for cardiac causes after radiation therapy was determined from hospitalization records. Ten- and 15-year cumulative hospital-related cardiac morbidity after radiation therapy was estimated for left- and right-sided cases using a competing risk approach. Results: The median follow-up was 13.2 years. For left-sided cases, 485 women were treated with CF-WBI, and 2221 women were treated with HF-WBI. Mastectomy was more common in the HF-WBI group, whereas boost was more common in the CF-WBI group. The CF-WBI group had a higher prevalence of diabetes. The 15-year cumulative hospital-related morbidity from cardiac causes (95% confidence interval) was not different between the 2 radiation therapy regimens after propensity-score adjustment: 21% (19-22) with HF-WBI and 21% (17-25) with CF-WBI (P=.93). For right-sided cases, the 15-year cumulative hospital-related morbidity from cardiac causes was also similar between the radiation therapy groups (P=.76). Conclusions: There is no difference in morbidity leading to hospitalization from cardiac causes among women with left-sided early-stage breast

  13. Adjuvant Hypofractionated Versus Conventional Whole Breast Radiation Therapy for Early-Stage Breast Cancer: Long-Term Hospital-Related Morbidity From Cardiac Causes

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Elisa K. [Department of Oncology, Saint John Regional Hospital, Saint John (Canada); Woods, Ryan; McBride, Mary L. [Cancer Control Research Department, BC Cancer Agency, Vancouver (Canada); Virani, Sean [Division of Cardiology, University of British Columbia, Vancouver (Canada); Nichol, Alan [Radiation Therapy Program, BC Cancer Agency, Vancouver (Canada); Speers, Caroline [Breast Cancer Outcomes Unit, BC Cancer Agency, Vancouver (Canada); Wai, Elaine S. [Radiation Therapy Program, BC Cancer Agency, Vancouver (Canada); Tyldesley, Scott, E-mail: styldesl@bccancer.bc.ca [Radiation Therapy Program, BC Cancer Agency, Vancouver (Canada)

    2014-03-15

    Purpose: The risk of cardiac injury with hypofractionated whole-breast/chest wall radiation therapy (HF-WBI) compared with conventional whole-breast/chest wall radiation therapy (CF-WBI) in women with left-sided breast cancer remains a concern. The purpose of this study was to determine if there is an increase in hospital-related morbidity from cardiac causes with HF-WBI relative to CF-WBI. Methods and Materials: Between 1990 and 1998, 5334 women ≤80 years of age with early-stage breast cancer were treated with postoperative radiation therapy to the breast or chest wall alone. A population-based database recorded baseline patient, tumor, and treatment factors. Hospital administrative records identified baseline cardiac risk factors and other comorbidities. Factors between radiation therapy groups were balanced using a propensity-score model. The first event of a hospital admission for cardiac causes after radiation therapy was determined from hospitalization records. Ten- and 15-year cumulative hospital-related cardiac morbidity after radiation therapy was estimated for left- and right-sided cases using a competing risk approach. Results: The median follow-up was 13.2 years. For left-sided cases, 485 women were treated with CF-WBI, and 2221 women were treated with HF-WBI. Mastectomy was more common in the HF-WBI group, whereas boost was more common in the CF-WBI group. The CF-WBI group had a higher prevalence of diabetes. The 15-year cumulative hospital-related morbidity from cardiac causes (95% confidence interval) was not different between the 2 radiation therapy regimens after propensity-score adjustment: 21% (19-22) with HF-WBI and 21% (17-25) with CF-WBI (P=.93). For right-sided cases, the 15-year cumulative hospital-related morbidity from cardiac causes was also similar between the radiation therapy groups (P=.76). Conclusions: There is no difference in morbidity leading to hospitalization from cardiac causes among women with left-sided early-stage breast

  14. Hypofractionated Adjuvant Whole Breast Radiotherapy: Progress and Prospects

    International Nuclear Information System (INIS)

    Yarnold, John; Haviland, Joanne

    2010-01-01

    Published results of randomised trials involving >7000 women confirm the safety and efficacy of hypofractionated schedules of adjuvant radiotherapy for women with early breast cancer using fraction sizes between 2 and 3 Gy assuming appropriate downward adjustments to total dose. Unnecessary concerns relating to heart tolerance, suboptimal dose distribution and duration of follow up need not discourage the routine adoption of 15- or 16-fraction schedules in women treated by breast conservation surgery for early breast cancer. Regardless of fractionation regimen, dose escalation to the index quadrant in high risk subgroups will result in a greater relative increase in late adverse effects than tumour control, a therapeutic disadvantage that can only be overcome by exploiting a marked dose-volume effect. A 15-fraction schedule of whole breast radiotherapy is unlikely to represent the lower limits of hypofractionation, and the preliminary results of a 5-fraction regimen are encouraging

  15. Hypo-fractionated treatment in radiotherapy: radio-biological models Tcp and NTCP

    International Nuclear Information System (INIS)

    Astudillo V, A. J.; Mitsoura, E.; Paredes G, L.; Resendiz G, G.

    2014-08-01

    At the present time the breast cancer in Mexico has the first place of incidence of the malignant neoplasia s in the women, and represents 11.34% of all the cancer cases. On the other hand, the treatments for cancer by means of ionizing radiations have been dominated under the approaches of the medical radio-oncologists which have been based on test and error by many years. The radio-biological models, as the Tcp, NTCP and dosimetric variables, for their clinical application in the conventional radiotherapy with hypo-fractionation have as purpose predicting personalized treatment plans that they present most probability of tumor control and minor probability of late reactions, becoming this way support tools in the decisions taking for the patient treatments planning of Medical Physicists and Radio-oncologists. (Author)

  16. Individualized planning target volumes for intrafraction motion during hypofractionated intensity-modulated radiotherapy boost for prostate cancer

    International Nuclear Information System (INIS)

    Cheung, Patrick; Sixel, Katharina; Morton, Gerard; Loblaw, D. Andrew; Tirona, Romeo; Pang, Geordi; Choo, Richard; Szumacher, Ewa; DeBoer, Gerrit; Pignol, Jean-Philippe

    2005-01-01

    Purpose: The objective of the study was to access toxicities of delivering a hypofractionated intensity-modulated radiotherapy (IMRT) boost with individualized intrafraction planning target volume (PTV) margins and daily online correction for prostate position. Methods and materials: Phase I involved delivering 42 Gy in 21 fractions using three-dimensional conformal radiotherapy, followed by a Phase II IMRT boost of 30 Gy in 10 fractions. Digital fluoroscopy was used to measure respiratory-induced motion of implanted fiducial markers within the prostate. Electronic portal images were taken of fiducial marker positions before and after each fraction of radiotherapy during the first 9 days of treatment to calculate intrafraction motion. A uniform 10-mm PTV margin was used for the first phase of treatment. PTV margins for Phase II were patient-specific and were calculated from the respiratory and intrafraction motion data obtained from Phase I. The IMRT boost was delivered with daily online correction of fiducial marker position. Acute toxicity was measured using National Cancer Institute Common Toxicity Criteria, version 2.0. Results: In 33 patients who had completed treatment, the average PTV margin used during the hypofractionated IMRT boost was 3 mm in the lateral direction, 3 mm in the superior-inferior direction, and 4 mm in the anteroposterior direction. No patients developed acute Grade 3 rectal toxicity. Three patients developed acute Grade 3 urinary frequency and urgency. Conclusions: PTV margins can be reduced significantly with daily online correction of prostate position. Delivering a hypofractionated boost with this high-precision IMRT technique resulted in acceptable acute toxicity

  17. High-Dose Hypofractionated Radiation Therapy for Noncompressive Vertebral Metastases in Combination With Zoledronate: A Phase 1 Study

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    Pichon, Baptiste [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); Campion, Loïc [Department of Biostatistics, ICO Cancer Center, Saint-Herblain (France); Delpon, Grégory [Department of Medical Physics, ICO Cancer Center, Saint-Herblain (France); CRCNA, Inserm U892, CNRS UMR 6299, Nantes (France); Thillays, François [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); Carrie, Christian [Department of Radiation Oncology, Léon Bérard Center, Lyon (France); Cellier, Patrice [Department of Radiation Oncology, ICO Cancer Center, Angers (France); Pommier, Pascal; Laude, Cécile [Department of Radiation Oncology, Léon Bérard Center, Lyon (France); Mervoyer, Augustin [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); Hamidou, Hadji [Department of Radiation Oncology, ICO Cancer Center, Angers (France); Mahé, Marc-André [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); Supiot, Stéphane, E-mail: stephane.supiot@ico.unicancer.fr [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); CRCNA, Inserm U892, CNRS UMR 6299, Nantes (France)

    2016-11-15

    Introduction: Hypofractionated stereotactic radiation therapy (HSRT) for vertebral metastases gives good results in terms of local control but increases the risk of fracture in the treated volume. Preclinical and clinical studies have shown that zoledronate not only reduces the risk of fracture and stimulates osteoclastic remodeling but also increases the immune response and radiosensitivity. This study aimed to evaluate the tolerability and effectiveness of zoledronate in association with radiation therapy. Patients and Methods: We conducted a multicenter phase 1 study that combined HSRT (3 × 9 Gy) and zoledronate in patients with vertebral metastasis ( (NCT01219790)). The principal objective was the absence of spinal cord adverse reactions at 1 year. The secondary objectives were acute tolerability, the presentation of a bone event, local tumor control, pain control, progression-free survival, and overall survival. Results: Thirty patients (25 male, 5 female), median age 66 years, who were followed up for a median period of 19.2 months, received treatment for 49 vertebral metastases. A grade 3 acute mucosal adverse event occurred in 1 patient during the treatment and in 2 more at 1 month. No late neurologic adverse events were reported at 1 year. The mean pain scores diminished significantly at 1 month (1.35; P=.0125) and 3 months (0.77; P<.0001) compared with pain scores at study entry (2.49). Vertebral collapse in the irradiated zone occurred in 1 (2%) treated vertebra. Control of local disease was achieved in 94% of irradiated patients (3 local recurrences). Conclusion: The combination of zoledronate and HSRT in the treatment of vertebral metastasis is well tolerated and seems to reduce the rate of vertebral collapse, effectively relieve pain, and achieve good local tumor control with no late neurologic adverse effects.

  18. Phase 2 Study of Accelerated Hypofractionated Thoracic Radiation Therapy and Concurrent Chemotherapy in Patients With Limited-Stage Small-Cell Lung Cancer

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    Xia, Bing [Department of Radiation Oncology, Shanghai Cancer Center, Fudan University, Shanghai (China); Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou (China); Hong, Ling-Zhi [Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing (China); Cai, Xu-Wei; Zhu, Zheng-Fei; Liu, Qi; Zhao, Kuai-Le; Fan, Min; Mao, Jing-Fang; Yang, Huan-Jun; Wu, Kai-Liang [Department of Radiation Oncology, Shanghai Cancer Center, Fudan University, Shanghai (China); Fu, Xiao-Long, E-mail: xlfu1964@hotmail.com [Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai (China)

    2015-03-01

    Purpose: To prospectively investigate the efficacy and toxicity of accelerated hypofractionated thoracic radiation therapy (HypoTRT) combined with concurrent chemotherapy in the treatment of limited-stage small-cell lung cancer (LS-SCLC), with the hypothesis that both high radiation dose and short radiation time are important in this setting. Methods and Materials: Patients with previously untreated LS-SCLC, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function were eligible. HypoTRT of 55 Gy at 2.5 Gy per fraction over 30 days was given on the first day of the second or third cycle of chemotherapy. An etoposide/cisplatin regimen was given to 4 to 6 cycles. Patients who had a good response to initial treatment were offered prophylactic cranial irradiation. The primary endpoint was the 2-year progression-free survival rate. Results: Fifty-nine patients were enrolled from July 2007 through February 2012 (median age, 58 years; 86% male). The 2-year progression-free survival rate was 49.0% (95% confidence interval [CI] 35.3%-62.7%). Median survival time was 28.5 months (95% CI 9.0-48.0 months); the 2-year overall survival rate was 58.2% (95% CI 44.5%-71.9%). The 2-year local control rate was 76.4% (95% CI 63.7%-89.1%). The severe hematologic toxicities (grade 3 or 4) were leukopenia (32%), neutropenia (25%), and thrombocytopenia (15%). Acute esophagitis and pneumonitis of grade ≥3 occurred in 25% and 10% of the patients, respectively. Thirty-eight patients (64%) received prophylactic cranial irradiation. Conclusion: Our study showed that HypoTRT of 55 Gy at 2.5 Gy per fraction daily concurrently with etoposide/cisplatin chemotherapy has favorable survival and acceptable toxicity. This radiation schedule deserves further investigation in LS-SCLC.

  19. Salvage Treatment With Hypofractionated Radiotherapy in Patients With Recurrent Small Hepatocellular Carcinoma

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    Bae, Sun Hyun [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, Hee Chul, E-mail: rophc@skku.edu [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lim, Do Hoon; Lee, Jung Ae [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Gwak, Geum Yeon; Choi, Moon Seok; Lee, Joon Hyoek; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul [Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-03-15

    Purpose: To investigate the rates of tumor response and local control in patients with recurrent small hepatocellular carcinoma (HCC) treated with hypofractionated radiotherapy (RT) as a salvage treatment and to evaluate treatment-related toxicities. Methods and Materials: Between 2006 and 2009, a total of 20 patients with recurrent small HCC were treated with hypofractionated RT after the failure of previous treatment. The eligibility criteria for hypofractionated RT were as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to critical organs, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that would be irradiated with 50% of prescribed dose. The RT dose was 50 Gy in 10 fractions. The tumor response was determined by CT scans performed 3 months after the end of RT. Results: The median follow-up period after RT was 22 months. The overall survival rates at 1 and 2 years were 100% and 87.9%, respectively. Complete response (CR) was achieved in seven of 20 lesions (35%) evaluated by CT scans performed 3 months after the end of RT. In-field local control was achieved in 85% of patients. Fourteen patients (70%) developed intra-hepatic metastases. Six patients developed grade 1 nausea or anorexia during RT, and two patients had progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusions: The current study showed a favorable outcome with respect to hypofractionated RT for small HCC. Partial liver irradiation with 50 Gy in 10 fractions is considered tolerable without severe complications.

  20. Salvage Treatment With Hypofractionated Radiotherapy in Patients With Recurrent Small Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Bae, Sun Hyun; Park, Hee Chul; Lim, Do Hoon; Lee, Jung Ae; Gwak, Geum Yeon; Choi, Moon Seok; Lee, Joon Hyoek; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul

    2012-01-01

    Purpose: To investigate the rates of tumor response and local control in patients with recurrent small hepatocellular carcinoma (HCC) treated with hypofractionated radiotherapy (RT) as a salvage treatment and to evaluate treatment-related toxicities. Methods and Materials: Between 2006 and 2009, a total of 20 patients with recurrent small HCC were treated with hypofractionated RT after the failure of previous treatment. The eligibility criteria for hypofractionated RT were as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to critical organs, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that would be irradiated with 50% of prescribed dose. The RT dose was 50 Gy in 10 fractions. The tumor response was determined by CT scans performed 3 months after the end of RT. Results: The median follow-up period after RT was 22 months. The overall survival rates at 1 and 2 years were 100% and 87.9%, respectively. Complete response (CR) was achieved in seven of 20 lesions (35%) evaluated by CT scans performed 3 months after the end of RT. In-field local control was achieved in 85% of patients. Fourteen patients (70%) developed intra-hepatic metastases. Six patients developed grade 1 nausea or anorexia during RT, and two patients had progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusions: The current study showed a favorable outcome with respect to hypofractionated RT for small HCC. Partial liver irradiation with 50 Gy in 10 fractions is considered tolerable without severe complications.

  1. Radiation-induced apoptosis

    International Nuclear Information System (INIS)

    Ohyama, Harumi

    1995-01-01

    Apoptosis is an active process of gene-directed cellular self-destruction that can be induced in many cell types via numerous physiological and pathological stimuli. We found that interphasedeath of thymocytes is a typical apoptosis showing the characteristic features of apoptosis including cell shrinkage, chromatin condensation and DNA degradation. Moderate dose of radiation induces extensive apoptosis in rapidly proliferating cell population such as the epithelium of intestinal crypt. Recent reports indicate that the ultimate form of radiation-induced mitotic death in several cells is also apoptosis. One of the hallmarks of apoptosis is the enzymatic internucleosomal degradation of chromatin DNA. We identified an endonuclease responsible for the radiation-induced DNA degradation in rat thymocytes. The death-sparing effects of interrupting RNA and protein synthesis suggested a cell genetic program for apoptosis. Apoptosis of thymocytes initiated by DNA damage, such as radiation and radio mimetic substance, absolutely requires the protein of p53 cancer suppresser gene. The cell death induced by glucocorticoid, or aging, has no such requirement. Expression of oncogene bcl-2 rescues cells from the apoptosis. Massive apoptosis in radiosensitive cells induced by higher dose radiation may be fatal. It is suggested that selective apoptotic elimination of cells would play an important role for protection against carcinogenesis and malformation through removal of cells with unrepaired radiation-induced DNA damages. Data to evaluate the significance of apoptosis in the radiation risk are still poor. Further research should be done in order to clarify the roles of the cell death on the acute and late effects of irradiation. (author)

  2. Hypofractionated whole breast irradiation: New standard in early breast cancer after breast-conserving surgery

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    Kim, Kyung Su; Shin, Kyung Hwan; Choi, Noorie; Lee, Sea Won [Dept. of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2016-06-15

    Hypofractionated whole breast irradiation (HF-WBI) has been proved effective and safe and even better for late or acute radiation toxicity for early breast cancer. Moreover, it improves patient convenience, quality of life and is expected to be advantageous in the medical care system by reducing overall cost. In this review, we examined key randomized trials of HF-WBI, focusing on adequate patient selection as suggested by the American Society of Therapeutic Radiology and Oncology (ASTRO) guideline and the radiobiologic aspects of HF-WBI in relation to its adoption into clinical settings. Further investigation to identify the current practice pattern or cost effectiveness is warranted under the national health insurance service system in Korea.

  3. Phase 1 Study of Dose Escalation in Hypofractionated Proton Beam Therapy for Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gillin, Michael [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wei, Caimiao [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H.; Swanick, Cameron; Alvarado, Tina; Komaki, Ritsuko; Cox, James D.; Chang, Joe Y. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-07-15

    Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Methods and Materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.

  4. Hypofractionated Intensity-Modulated Radiotherapy for Carcinoma of the Prostate: Analysis of Toxicity

    International Nuclear Information System (INIS)

    Coote, Joanna H.; Wylie, James P.; Cowan, Richard A.; Logue, John P.; Swindell, Ric; Livsey, Jacqueline E.

    2009-01-01

    Purpose: Dose escalation for prostate cancer improves biological control but with a significant increase in late toxicity. Recent estimates of low α/β ratio for prostate cancer suggest that hypofractionation may result in biological advantage. Intensity-modulated radiotherapy (IMRT) should enable dose escalation to the prostate while reducing toxicity to local organs. We report late toxicity data of a hypofractionated IMRT regime. Methods and Materials: Eligible men had T2-3N0M0 adenocarcinoma prostate, and either Gleason score ≥ 7 or prostate-specific antigen 20-50 ng/L. Patients received 57-60 Gy to prostate in 19-20 fractions using five-field IMRT. All received hormonal therapy for 3 months before radiotherapy to a maximum of 6 months. Toxicity was assessed 2 years postradiotherapy using the RTOG criteria, LENT/SOMA, and UCLA prostate index assessment tools. Results: Acute toxicity was favorable with no RTOG Grade 3 or 4 toxicity. At 2 years, there was 4% Grade 2 bowel and 4.25% Grade 2 bladder toxicity. There was no Grade 3 or 4 bowel toxicity; one patient developed Grade 3 bladder toxicity. UCLA data showed a slight improvement in urinary function at 2 years compared with pretreatment. LENT/SOMA assessments demonstrated general worsening of bowel function at 2 years. Patients receiving 60 Gy were more likely to develop problems with bowel function than those receiving 57 Gy. Conclusions: These data demonstrate that hypofractionated radiotherapy using IMRT for prostate cancer is well tolerated with minimal late toxicity at 2 years posttreatment. Ongoing studies are looking at the efficacy of hypofractionated regimes with respect to biological control.

  5. Outcome analysis of 300 prostate cancer patients treated with neoadjuvant androgen deprivation and hypofractionated radiotherapy

    International Nuclear Information System (INIS)

    Higgins, Geoffrey S.; McLaren, Duncan B.; Kerr, Gillian R.; Elliott, Tony; Howard, Grahame

    2006-01-01

    Purpose: Neoadjuvant androgen deprivation and radical radiotherapy is an established treatment for localized prostate carcinoma. This study sought to analyze the outcomes of patients treated with relatively low-dose hypofractionated radiotherapy. Methods and Materials: Three hundred patients with T1-T3 prostate cancer were treated between 1996 and 2001. Patients were prescribed 3 months of neoadjuvant androgen deprivation before receiving 5250 cGy in 20 fractions. Patients' case notes and the oncology database were used to retrospectively assess outcomes. Median follow-up was 58 months. Results: Patients presented with prostate cancer with poorer prognostic indicators than that reported in other series. At 5 years, the actuarial cause-specific survival rate was 83.2% and the prostate-specific antigen (PSA) relapse rate was 57.3%. Metastatic disease had developed in 23.4% of patients. PSA relapse continued to occur 5 years from treatment in all prognostic groups. Independent prognostic factors for relapse included treatment near the start of the study period, neoadjuvant oral anti-androgen monotherapy rather than neoadjuvant luteinizing hormone releasing hormone therapy, and diagnosis through transurethral resection of the prostate rather than transrectal ultrasound. Conclusion: This is the largest reported series of patients treated with neoadjuvant androgen deprivation and hypofractionated radiotherapy in the United Kingdom. Neoadjuvant hormonal therapy did not appear to adequately compensate for the relatively low effective radiation dose used

  6. Outcomes of Modestly Hypofractionated Radiation for Lung Tumors: Pre- and Mid-Treatment Positron Emission Tomography-Computed Tomography Metrics as Prognostic Factors.

    Science.gov (United States)

    Harris, Jeremy P; Chang-Halpenny, Christine N; Maxim, Peter G; Quon, Andrew; Graves, Edward E; Diehn, Maximilian; Loo, Billy W

    2015-11-01

    Many patients with lung tumors have tumors too large for stereotactic ablative radiotherapy and comorbidities precluding concurrent chemotherapy. We report the outcomes of 29 patients treated with hypofractionated radiotherapy (RT) to 60 to 66 Gy in 3-Gy fractions. We also report an exploratory analysis of the prognostic value of the pre- and mid-RT positron emission tomography-computed tomography. Modestly hypofractionated radiation therapy (HypoRT; 60-66 Gy in 3-Gy fractions) allows patients with locally advanced thoracic tumors and poor performance status to complete treatment within a shorter period without concurrent chemotherapy. We evaluated the outcomes and imaging prognostic factors of HypoRT. We retrospectively reviewed the data from all patients with primary and metastatic intrathoracic tumors treated with HypoRT from 2006 to 2012. We analyzed the survival and toxicity outcomes, including overall survival (OS), progression-free survival (PFS), local recurrence (LR), and distant metastasis. We also evaluated the following tumor metrics in an exploratory analysis: gross tumor volume (GTV), maximum standardized uptake value (SUVMax), and metabolic tumor volume using a threshold of ≥ 50% of the SUVMax (MTV50%) or the maximum gradient of fluorine-18 fluorodeoxyglucose uptake (MTVEdge). We assessed the association of these metrics and their changes from before to mid-RT using positron emission tomography-computed tomography (PET-CT) with OS and PFS. We identified 29 patients, all with pre-RT and 20 with mid-RT PET-CT scans. The median follow-up period was 15 months. The 2-year overall and non-small-cell lung cancer-only rate for OS, PFS, and LR, was 59% and 59%, 52% and 41%, and 27% and 32%, respectively. No grade ≥ 3 toxicities developed. The median decrease in GTV, SUVMax, and MTVEdge was 11%, 24%, and 18%, respectively. Inferior OS was associated with a larger pre-RT MTVEdge (P = .005) and pre-RT MTV50% (P = .007). Inferior PFS was associated with a

  7. Moderate Hypofractionated Protracted Radiation Therapy and Dose Escalation for Prostate Cancer: Do Dose and Overall Treatment Time Matter?

    Energy Technology Data Exchange (ETDEWEB)

    Kountouri, Melpomeni; Zilli, Thomas; Rouzaud, Michel; Dubouloz, Angèle [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Linero, Dolors; Escudé, Lluís; Jorcano, Sandra [Radiation Oncology, Teknon Oncologic Institute, Barcelona (Spain); Miralbell, Raymond, E-mail: Raymond.Miralbell@hcuge.ch [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Radiation Oncology, Teknon Oncologic Institute, Barcelona (Spain)

    2016-02-01

    Purpose: This was a retrospective study of 2 sequential dose escalation regimens of twice-weekly 4 Gy/fractions hypofractionated intensity modulated radiation therapy (IMRT): 56 Gy and 60 Gy delivered within a protracted overall treatment time (OTT) of 6.5 and 7 weeks, respectively. Methods and Materials: 163 prostate cancer patients with cT1c-T3a disease and nodal involvement risk ≤20% (Roach index) were treated twice weekly to the prostate ± seminal vesicles with 2 sequential dose-escalated IMRT schedules: 56 Gy (14 × 4 Gy, n=81) from 2003 to 2007 and 60 Gy (15 × 4 Gy, n=82) from 2006 to 2010. Patient repositioning was made with bone matching on portal images. Gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3.0 grading scale. Results: There were no significant differences regarding the acute GU and GI toxicities in the 2 dose groups. The median follow-up times were 80.2 months (range, 4.5-121 months) and 56.5 months (range, 1.4-91.2 months) for patients treated to 56 and 60 Gy, respectively. The 5-year grade ≥2 late GU toxicity-free survivals with 56 Gy and 60 Gy were 96 ± 2.3% and 78.2 ± 5.1% (P=.001), respectively. The 5-year grade ≥2 late GI toxicity-free survivals with 56 Gy and 60 Gy were 98.6 ± 1.3% and 85.1 ± 4.5% (P=.005), respectively. Patients treated with 56 Gy showed a 5-year biochemical progression-free survival (bPFS) of 80.8 ± 4.7%, worse than patients treated with 60 Gy (93.2 ± 3.9%, P=.007). A trend for a better 5-year distant metastasis-free survival was observed among patients treated in the high-dose group (95.3 ± 2.7% vs 100%, P=.073, respectively). On multivariate analysis, only the 60-Gy group predicted for a better bPFS (P=.016, hazard ratio = 4.58). Conclusions: A single 4-Gy additional fraction in patients treated with a hypofractionated protracted IMRT schedule of 14 × 4 Gy resulted in

  8. A biologically competitive 21 days hypofractionation scheme with weekly concomitant boost in breast cancer radiotherapy feasibility acute sub-acute and short term late effects

    International Nuclear Information System (INIS)

    Guenzi, Marina; Vagge, Stefano; Azinwi, Ngwa Che; D'Alonzo, Alessia; Belgioia, Liliana; Garelli, Stefania; Gusinu, Marco; Corvò, Renzo

    2010-01-01

    Radiation therapy after lumpectomy is a standard part of breast conserving therapy for invasive breast carcinoma. The most frequently used schedule worldwide is 60 Gy in 30 fractions in 6 weeks, a time commitment that sporadically may dissuade some otherwise eligible women from undertaking treatment. The purpose and primary endpoint of this perspective study is to evaluate feasibility and short-term late toxicity in a hypofractionated whole breast irradiation schedule. Between February and October 2008 we treated 65 consecutive patients with operable invasive early-stage breast cancer with a hypofractionated schedule of external beam radiation therapy. All patients were assigned to 39 Gy in 13 fractions in 3 weeks to the whole breast plus a concomitant weekly boost dose to the lumpectomy cavity of 3 Gy in 3 fractions. All the patients had achieved a median follow up of 24 months (range 21-29 months). At the end of treatment 52% presented grade 0 acute toxicity 39% had grade 1 and 9% had grade 2. At 6 months with all the patients assessed there were 34% case of grade 1 subacute toxicity and 6% of grade 2. At 12 months 43% and 3% of patients presented with clinical grade 1 and grade 2 fibrosis respectively and 5% presented grade 1 hyperpigmentation. The remaining patients were free of side effects. At 24 months, with 56 assessed, just 2 patients (3%) showed grade 2 of late fibrosis. The clinical results observed showed a reasonably good feasibility of the accelerated hypofractionated schedule in terms of acute, subacute and short-term late toxicity. This useful 13 fractions with a concomitant boost schedule seems, in selected patients, a biologically acceptable alternative to the traditional 30 days regime

  9. Hypofractionated stereotactic radiotherapy in five daily fractions for post-operative surgical cavities in brain metastases patients with and without prior whole brain radiation.

    Science.gov (United States)

    Al-Omair, Ameen; Soliman, Hany; Xu, Wei; Karotki, Aliaksandr; Mainprize, Todd; Phan, Nicolas; Das, Sunit; Keith, Julia; Yeung, Robert; Perry, James; Tsao, May; Sahgal, Arjun

    2013-12-01

    Our purpose was to report efficacy of hypofractionated cavity stereotactic radiotherapy (HCSRT) in patients with and without prior whole brain radiotherapy (WBRT). 32 surgical cavities in 30 patients (20 patients/21 cavities had no prior WBRT and 10 patients/11 cavities had prior WBRT) were treated with image-guided linac stereotactic radiotherapy. 7 of the 10 prior WBRT patients had "resistant" local disease given prior surgery, post-operative WBRT and a re-operation, followed by salvage HCSRT. The clinical target volume was the post-surgical cavity, and a 2-mm margin applied as planning target volume. The median total dose was 30 Gy (range: 25-37.5 Gy) in 5 fractions. In the no prior and prior WBRT cohorts, the median follow-up was 9.7 months (range: 3.0-23.6) and 15.3 months (range: 2.9-39.7), the median survival was 23.6 months and 39.7 months, and the 1-year cavity local recurrence progression- free survival (LRFS) was 79 and 100%, respectively. At 18 months the LRFS dropped to 29% in the prior WBRT cohort. Grade 3 radiation necrosis occurred in 3 prior WBRT patients. We report favorable outcomes with HCSRT, and well selected patients with prior WBRT and "resistant" disease may have an extended survival favoring aggressive salvage HCSRT at a moderate risk of radiation necrosis.

  10. Phase I Trial of Pelvic Nodal Dose Escalation With Hypofractionated IMRT for High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Adkison, Jarrod B.; McHaffie, Derek R.; Bentzen, Soren M.; Patel, Rakesh R.; Khuntia, Deepak [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, Madison, WI (United States); Petereit, Daniel G. [Department of Radiation Oncology, John T. Vucurevich Regional Cancer Care Institute, Rapid City Regional Hospital, Rapid City, SD (United States); Hong, Theodore S.; Tome, Wolfgang [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, Madison, WI (United States); Ritter, Mark A., E-mail: ritter@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, Madison, WI (United States)

    2012-01-01

    Purpose: Toxicity concerns have limited pelvic nodal prescriptions to doses that may be suboptimal for controlling microscopic disease. In a prospective trial, we tested whether image-guided intensity-modulated radiation therapy (IMRT) can safely deliver escalated nodal doses while treating the prostate with hypofractionated radiotherapy in 5 Vulgar-Fraction-One-Half weeks. Methods and Materials: Pelvic nodal and prostatic image-guided IMRT was delivered to 53 National Comprehensive Cancer Network (NCCN) high-risk patients to a nodal dose of 56 Gy in 2-Gy fractions with concomitant treatment of the prostate to 70 Gy in 28 fractions of 2.5 Gy, and 50 of 53 patients received androgen deprivation for a median duration of 12 months. Results: The median follow-up time was 25.4 months (range, 4.2-57.2). No early Grade 3 Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events v.3.0 genitourinary (GU) or gastrointestinal (GI) toxicities were seen. The cumulative actuarial incidence of Grade 2 early GU toxicity (primarily alpha blocker initiation) was 38%. The rate was 32% for Grade 2 early GI toxicity. None of the dose-volume descriptors correlated with GU toxicity, and only the volume of bowel receiving {>=}30 Gy correlated with early GI toxicity (p = 0.029). Maximum late Grades 1, 2, and 3 GU toxicities were seen in 30%, 25%, and 2% of patients, respectively. Maximum late Grades 1 and 2 GI toxicities were seen in 30% and 8% (rectal bleeding requiring cautery) of patients, respectively. The estimated 3-year biochemical control (nadir + 2) was 81.2 {+-} 6.6%. No patient manifested pelvic nodal failure, whereas 2 experienced paraaortic nodal failure outside the field. The six other clinical failures were distant only. Conclusions: Pelvic IMRT nodal dose escalation to 56 Gy was delivered concurrently with 70 Gy of hypofractionated prostate radiotherapy in a convenient, resource-efficient, and well-tolerated 28-fraction schedule. Pelvic nodal dose

  11. Optimal hypofractionated conformal radiotherapy for large brain metastases in patients with high risk factors: a single-institutional prospective study

    International Nuclear Information System (INIS)

    Inoue, Hiroshi K; Sato, Hiro; Suzuki, Yoshiyuki; Saitoh, Jun-ichi; Noda, Shin-ei; Seto, Ken-ichi; Torikai, Kota; Sakurai, Hideyuki; Nakano, Takashi

    2014-01-01

    A single-institutional prospective study of optimal hypofractionated conformal radiotherapy for large brain metastases with high risk factors was performed based on the risk prediction of radiation-related complications. Eighty-eight patients with large brain metastases ≥10 cm 3 in critical areas treated from January 2010 to February 2014 using the CyberKnife were evaluated. The optimal dose and number of fractions were determined based on the surrounding brain volume circumscribed with a single dose equivalent (SDE) of 14 Gy (V14) to be less than 7 cm 3 for individual lesions. Univariate and multivariate analyses were conducted. As a result of optimal treatment, 92 tumors ranging from 10 to 74.6 cm 3 (median, 16.2 cm 3 ) in volume were treated with a median prescribed isodose of 57% and a median fraction number of five. In order to compare the results according to the tumor volume, the tumors were divided into the following three groups: 1) 10–19.9 cm 3 , 2) 20–29.9 cm 3 and 3) ≥30 cm 3 . The lesions were treated with a median prescribed isodose of 57%, 56% and 55%, respectively, and the median fraction number was five in all three groups. However, all tumors ≥20 cm 3 were treated with ≥ five fractions. The median SDE of the maximum dose in the three groups was 47.2 Gy, 48.5 Gy and 46.5 Gy, respectively. Local tumor control was obtained in 90.2% of the patients, and the median survival was nine months, with a median follow-up period of seven months (range, 3-41 months). There were no significant differences in the survival rates among the three groups. Six tumors exhibited marginal recurrence 7-36 months after treatment. Ten patients developed symptomatic brain edema or recurrence of pre-existing edema, seven of whom required osmo-steroid therapy. No patients developed radiation necrosis requiring surgical resection. Our findings demonstrate that the administration of optimal hypofractionated conformal radiotherapy based on the dose-volume prediction

  12. Long-term Outcomes of Hypofractionation Versus Conventional Radiation Therapy After Breast-Conserving Surgery for Ductal Carcinoma In Situ of the Breast

    Energy Technology Data Exchange (ETDEWEB)

    Lalani, Nafisha; Paszat, Lawrence [University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Institute for Clinical Evaluative Sciences, Toronto, Ontario (Canada); Sutradhar, Rinku; Thiruchelvam, Deva [Institute for Clinical Evaluative Sciences, Toronto, Ontario (Canada); Nofech-Mozes, Sharon; Hanna, Wedad; Slodkowska, Elzbieta [University of Toronto, Toronto, Ontario (Canada); Department of Anatomic Pathology, Sunnybrook Health Sciences Centre and Department of Laboratory Medicine and Pathobiology, Toronto, Ontario (Canada); Done, Susan J. [University of Toronto, Toronto, Ontario (Canada); Laboratory Medicine Program, University Health Network and Department of Laboratory Medicine and Pathobiology, Campbell Family Institute for Breast Cancer Research, Toronto, Ontario (Canada); Miller, Naomi; Youngson, Bruce [University of Toronto, Toronto, Ontario (Canada); Laboratory Medicine Program, University Health Network and Department of Laboratory Medicine and Pathobiology, Toronto, Ontario (Canada); Tuck, Alan [Pathology and Laboratory Medicine, London Health Sciences Centre and Saint Joseph' s Health Care, London, Ontario (Canada); Sengupta, Sandip [Department of Pathology and Molecular Medicine, Kingston General Hospital, Kingston, Ontario (Canada); Elavathil, Leela [Department of Anatomical Pathology, Juravinski Hospital, Hamilton Health Sciences, Hamilton, Ontario (Canada); Chang, Martin C. [Department of Pathology and Laboratory Medicine, Mount Sinai Hospital and Department of Laboratory Medicine and Pathobiology, Toronto, Ontario (Canada); Jani, Prashant A. [Department of Anatomical Pathology, Thunder Bay Regional Health Sciences Centre, Thunder Bay, Ontario (Canada); Bonin, Michel [Pathology and Laboratory Medicine, Sudbury Regional Hospital, Sudbury, Ontario (Canada); and others

    2014-12-01

    Purpose: Whole-breast radiation therapy (XRT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) may decrease the risk of local recurrence, but the optimal dose regimen remains unclear. Past studies administered 50 Gy in 25 fractions (conventional); however, treatment pattern studies report that hypofractionated (HF) regimens (42.4 Gy in 16 fractions) are frequently used. We report the impact of HF (vs conventional) on the risk of local recurrence after BCS for DCIS. Methods and Materials: All women with DCIS treated with BCS and XRT in Ontario, Canada from 1994 to 2003 were identified. Treatment and outcomes were assessed through administrative databases and validated by chart review. Survival analyses were performed. To account for systematic differences between women treated with alternate regimens, we used a propensity score adjustment approach. Results: We identified 1609 women, of whom 971 (60%) received conventional regimens and 638 (40%) received HF. A total of 489 patients (30%) received a boost dose, of whom 143 (15%) received conventional radiation therapy and 346 (54%) received HF. The median follow-up time was 9.2 years. The median age at diagnosis was 56 years (interquartile range [IQR], 49-65 years). On univariate analyses, the 10-year actuarial local recurrence–free survival was 86% for conventional radiation therapy and 89% for HF (P=.03). On multivariable analyses, age <45 years (hazard ratio [HR] = 2.4; 95% CI: 1.6-3.4; P<.0001), high (HR=2.9; 95% CI: 1.2-7.3; P=.02) or intermediate nuclear grade (HR=2.7; 95% CI: 1.1-6.6; P=.04), and positive resection margins (HR=1.4; 95% CI: 1.0-2.1; P=.05) were associated with an increased risk of local recurrence. HF was not significantly associated with an increased risk of local recurrence compared with conventional radiation therapy on multivariate analysis (HR=0.8; 95% CI: 0.5-1.2; P=.34). Conclusions: The risk of local recurrence among individuals treated with HF regimens

  13. Long-term Outcomes of Hypofractionation Versus Conventional Radiation Therapy After Breast-Conserving Surgery for Ductal Carcinoma In Situ of the Breast

    International Nuclear Information System (INIS)

    Lalani, Nafisha; Paszat, Lawrence; Sutradhar, Rinku; Thiruchelvam, Deva; Nofech-Mozes, Sharon; Hanna, Wedad; Slodkowska, Elzbieta; Done, Susan J.; Miller, Naomi; Youngson, Bruce; Tuck, Alan; Sengupta, Sandip; Elavathil, Leela; Chang, Martin C.; Jani, Prashant A.; Bonin, Michel

    2014-01-01

    Purpose: Whole-breast radiation therapy (XRT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) may decrease the risk of local recurrence, but the optimal dose regimen remains unclear. Past studies administered 50 Gy in 25 fractions (conventional); however, treatment pattern studies report that hypofractionated (HF) regimens (42.4 Gy in 16 fractions) are frequently used. We report the impact of HF (vs conventional) on the risk of local recurrence after BCS for DCIS. Methods and Materials: All women with DCIS treated with BCS and XRT in Ontario, Canada from 1994 to 2003 were identified. Treatment and outcomes were assessed through administrative databases and validated by chart review. Survival analyses were performed. To account for systematic differences between women treated with alternate regimens, we used a propensity score adjustment approach. Results: We identified 1609 women, of whom 971 (60%) received conventional regimens and 638 (40%) received HF. A total of 489 patients (30%) received a boost dose, of whom 143 (15%) received conventional radiation therapy and 346 (54%) received HF. The median follow-up time was 9.2 years. The median age at diagnosis was 56 years (interquartile range [IQR], 49-65 years). On univariate analyses, the 10-year actuarial local recurrence–free survival was 86% for conventional radiation therapy and 89% for HF (P=.03). On multivariable analyses, age <45 years (hazard ratio [HR] = 2.4; 95% CI: 1.6-3.4; P<.0001), high (HR=2.9; 95% CI: 1.2-7.3; P=.02) or intermediate nuclear grade (HR=2.7; 95% CI: 1.1-6.6; P=.04), and positive resection margins (HR=1.4; 95% CI: 1.0-2.1; P=.05) were associated with an increased risk of local recurrence. HF was not significantly associated with an increased risk of local recurrence compared with conventional radiation therapy on multivariate analysis (HR=0.8; 95% CI: 0.5-1.2; P=.34). Conclusions: The risk of local recurrence among individuals treated with HF regimens

  14. Ten-year results of accelerated hypofractionated adjuvant whole-breast radiation with concomitant boost to the lumpectomy cavity after conserving surgery for early breast cancer.

    Science.gov (United States)

    Cante, Domenico; Petrucci, Edoardo; Sciacero, Piera; Piva, Cristina; Ferrario, Silvia; Bagnera, Silvia; Patania, Sebastiano; Mondini, Guido; Pasquino, Massimo; Casanova Borca, Valeria; Vellani, Giorgio; La Porta, Maria Rosa; Franco, Pierfrancesco

    2017-09-01

    Accelerated hypofractionated whole-breast radiotherapy (WBRT) is considered a standard therapeutic option for early breast cancer (EBC) in the postoperative setting after breast conservation (BCS). A boost to the lumpectomy cavity may further increase local control. We herein report on the 10-year results of a series of EBC patients treated after BCS with hypofractionated WBRT with a concomitant photon boost to the surgical bed over 4 weeks. Between 2005 and 2007, 178 EBC patients were treated with a basic course of radiotherapy consisting of 45 Gy to the whole breast in 20 fractions (2.25 Gy daily) with an additional boost dose of 0.25 Gy delivered concomitantly to the lumpectomy cavity, for an additional dose of 5 Gy. Median follow-up period was 117 months. At 10-year, overall, cancer-specific, disease-free survival and local control were 92.2% (95% CI 88.7-93.4%), 99.2% (95% CI 96.7-99.7%), 95.5% (95% CI 91.2-97.2%) and 97.3% (95% CI 94.5-98.9%), respectively. Only eight patients recurred. Four in-breast recurrences, two axillary node relapses and two metastatic localizations were observed. Fourteen patients died during the observation period due to other causes while breast cancer-related deaths were eight. At last follow-up, ≥G2 fibrosis and telangiectasia were seen in 7% and 5% of patients. No major lung and heart toxicities were observed. Cosmetic results were excellent/good in 87.8% of patients and fair/poor in 12.2%. Hypofractionated WBRT with concomitant boost to the lumpectomy cavity after BCS in EBC led to consistent clinical results at 10 years. Hence, it can be considered a valid treatment option in this setting.

  15. Individualized Dose Prescription for Hypofractionation in Advanced Non-Small-Cell Lung Cancer Radiotherapy: An in silico Trial

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, Aswin L.; Troost, Esther G.C.; Huizenga, Henk; Kaanders, Johannes H.A.M. [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands); Bussink, Johan, E-mail: j.bussink@rther.umcn.nl [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands)

    2012-08-01

    Purpose: Local tumor control and outcome remain poor in patients with advanced non-small-cell lung cancer (NSCLC) treated by external beam radiotherapy. We investigated the therapeutic gain of individualized dose prescription with dose escalation based on normal tissue dose constraints for various hypofractionation schemes delivered with intensity-modulated radiation therapy. Methods and Materials: For 38 Stage III NSCLC patients, the dose level of an existing curative treatment plan with standard fractionation (66 Gy) was rescaled based on dose constraints for the lung, spinal cord, esophagus, brachial plexus, and heart. The effect on tumor total dose (TTD) and biologic tumor effective dose in 2-Gy fractions (TED) corrected for overall treatment time (OTT) was compared for isotoxic and maximally tolerable schemes given in 15, 20, and 33 fractions. Rescaling was accomplished by altering the dose per fraction and/or the number of fractions while keeping the relative dose distribution of the original treatment plan. Results: For 30 of the 38 patients, dose escalation by individualized hypofractionation yielded therapeutic gain. For the maximally tolerable dose scheme in 33 fractions (MTD{sub 33}), individualized dose escalation resulted in a 2.5-21% gain in TTD. In the isotoxic schemes, the number of fractions could be reduced with a marginal increase in TED. For the maximally tolerable dose schemes, the TED could be escalated up to 36.6%, and for all patients beyond the level of the isotoxic and the MTD{sub 33} schemes (range, 3.3-36.6%). Reduction of the OTT contributed to the therapeutic gain of the shortened schemes. For the maximally tolerable schemes, the maximum esophageal dose was the dominant dose-limiting constraint in most patients. Conclusions: This modeling study showed that individualized dose prescription for hypofractionation in NSCLC radiotherapy, based on scaling of existing treatment plans up to normal tissue dose constraints, enables dose

  16. Accelerated hypofractionated radiation therapy (AHRT) for non-small-cell lung cancer: can we leave standard fractionation?

    Science.gov (United States)

    de Dios, N Rodríguez; Sanz, X; Foro, P; Membrive, I; Reig, A; Ortiz, A; Jiménez, R; Algara, M

    2017-04-01

    To report interim results from a single-institution study conducted to assess accelerated hypofractionated radiotherapy (AHRT) delivered with 3D conformal radiotherapy in two groups of patients with non-small cell lung cancer: (1) patients with early stage disease unable to tolerate surgery and ineligible for stereotactic body radiation therapy, and (2) patients with locally advanced disease unsuitable for concurrent chemoradiotherapy. A total of 83 patients (51 stage I-II, 32 stage III) were included. Radiotherapy targets included the primary tumor and positive mediastinal areas identified on the pre-treatment PET-CT. Mean age was 77.8 ± 7.8 years. ECOG performance status (PS) was ≥2 in 50.6 % of cases. Radiotherapy was delivered in daily fractions of 2.75 Gy to a total dose of 66 Gy (BED 10 84 Gy). Acute and late toxicities were evaluated according to NCI CTC criteria. At a median follow-up of 42 months, median overall survival (OS) and cause-specific survival (CSS) were 23 and 36 months, respectively. On the multivariate analysis, PS [HR 4.14, p = 0.0001)], stage [HR 2.51, p = 0.005)], and maximum standardized uptake values (SUVmax) [HR 1.04, p = 0.04)] were independent risk factors for OS. PS [HR 5.2, p = 0.0001)] and stage [HR 6.3, p = 0.0001)] were also associated with CSS. No cases of severe acute or late treatment-related toxicities were observed. OS and CSS rates in patients treated with AHRT for stage I-II and stage III NSCLC were good. Treatment was well tolerated with no grade three or higher treatment-related toxicity. PS, stage, and SUV max were predictive for OS and CSS.

  17. Radiation-induced thermoacoustic imaging

    International Nuclear Information System (INIS)

    Bowen, T.

    1984-01-01

    This invention provides a new technique for obtaining information non-invasively on the composition and structures of a material or body by detecting radiation-induced thermoacoustic image features. This is accomplished by utilizing the acoustic wave generated by sudden thermal stress. The sudden thermal stress is induced by a pulse of radiation which deposits energy causing a rapid, but very small, rise of temperature (typically, ΔT approximately 10sup(-6) - 10sup(-5) deg C). The radiation may be ionizing radiation, such as high energy electrons, photons (x-rays), neutrons, or other charged particles or it may be non-ionizing radiation, such as R.F. and microwave electromagnetic radiation and ultrasonic radiation. The choice of radiation depends on the nature of the body to be imaged and the type of information desired

  18. Dosimetric Feasibility of Hypofractionated Proton Radiotherapy for Neoadjuvant Pancreatic Cancer Treatment

    International Nuclear Information System (INIS)

    Kozak, Kevin R.; Kachnic, Lisa A.; Adams, Judith C; Crowley, Elizabeth M.; Alexander, Brian M.; Mamon, Harvey J.; Fernandez-Del Castillo, Carlos; Ryan, David P.; DeLaney, Thomas F.; Hong, Theodore S.

    2007-01-01

    Purpose: To evaluate tumor and normal tissue dosimetry of a 5 cobalt gray equivalent (CGE) x 5 fraction proton radiotherapy schedule, before initiating a clinical trial of neoadjuvant, short-course proton radiotherapy for pancreatic adenocarcinoma. Methods and Materials: The first 9 pancreatic cancer patients treated with neoadjuvant intensity-modulated radiotherapy (1.8 Gy x 28) at the Massachusetts General Hospital had treatment plans generated using a 5 CGE x 5 fraction proton regimen. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing. Results: Hypofractionated proton and conventionally fractionated intensity-modulated radiotherapy plans both provided acceptable target volume coverage and dose homogeneity. Improved dose conformality provided by the hypofractionated proton regimen resulted in significant sparing of kidneys, liver, and small bowel, evidenced by significant reductions in the mean doses, expressed as percentage prescribed dose, to these structures. Kidney and liver sparing was most evident in low-dose regions (≤20% prescribed dose for both kidneys and ≤60% prescribed dose for liver). Improvements in small-bowel dosimetry were observed in high- and low-dose regions. Mean stomach and duodenum doses, expressed as percentage prescribed dose, were similar for the two techniques. Conclusions: A proton radiotherapy schedule consisting of 5 fractions of 5 CGE as part of neoadjuvant therapy for adenocarcinoma of the pancreas seems dosimetrically feasible, providing excellent target volume coverage, dose homogeneity, and normal tissue sparing. Hypofractionated proton radiotherapy in this setting merits Phase I clinical trial investigation

  19. Rectal bleeding after hypofractionated radiotherapy for prostate cancer: Correlation between clinical and dosimetric parameters and the incidence of grade 2 or worse rectal bleeding

    International Nuclear Information System (INIS)

    Akimoto, Tetsuo; Muramatsu, Hiroyuki; Takahashi, Mitsuhiro; Saito, Jun-ichi; Kitamoto, Yoshizumi; Harashima, Koichi; Miyazawa, Yasushi; Yamada, Masami; Ito, Kazuto; Kurokawa, Kouhei; Yamanaka, Hidetoshi; Nakano, Takashi; Mitsuhashi, Norio; Niibe, Hideo

    2004-01-01

    Purpose: To investigate the incidence and severity of rectal bleeding after high-dose hypofractionated radiotherapy (RT) for prostate cancer, and to explore the factors affecting the incidence of Grade 2 or worse rectal bleeding. Methods and materials: The data of 52 patients who had been treated by external beam RT for localized prostate cancer between 1999 and 2002 were analyzed. All the patients had received hypofractionated external beam RT to a total dose of 69 Gy in 3-Gy fractions, three fractions weekly. The clinical and dosimetric factors affecting the incidence of Grade 2 or worse late rectal bleeding were analyzed by univariate and multivariate analyses. The effect of the percentage of the whole rectal volume receiving 30%, 50%, 80%, and 90% of the prescribed radiation dose (V 30 , V 50 , V 80 , and V 90 , respectively) on the incidence of rectal bleeding was evaluated. Results: Of the 52 patients, 13 (25%) developed Grade 2 or worse rectal bleeding. One patient who needed laser coagulation and blood transfusion for the treatment of rectal bleeding was classified as having Grade 3 rectal bleeding. The median time to the development of Grade 2 or worse rectal bleeding was 11 months. The results of the univariate analysis revealed that the presence of a history of diabetes mellitus (p 30 ≥ 60%, V 50 ≥ 40% (p 80 ≥ 25%, and V 90 ≥ 15% (p < 0.001) were statistically significant risk factors for the occurrence of Grade 2 or worse rectal bleeding. The results of the multivariate analysis revealed that a history of diabetes mellitus was the most statistically significant risk factor for the occurrence of rectal bleeding after hypofractionated RT for prostate cancer (p < 0.05). Conclusion: A history of diabetes mellitus was the most statistically significant risk factor for the occurrence of Grade 2 or worse rectal bleeding after high-dose hypofractionated RT, although dosimetric factors were also closely associated with the risk of rectal bleeding

  20. The use of hypofractionated intensity-modulated irradiation in the treatment of glioblastoma multiforme: preliminary results of a prospective trial.

    Science.gov (United States)

    Sultanem, Khalil; Patrocinio, Horacio; Lambert, Christine; Corns, Robert; Leblanc, Richard; Parker, William; Shenouda, George; Souhami, Luis

    2004-01-01

    Despite major advances in treatment modalities, the prognosis of patients with glioblastoma multiforme (GBM) remains poor. Exploring hypofractionated regimens to replace the standard 6-week radiotherapy schedule is an attractive strategy as an attempt to prevent accelerated tumor cell repopulation. There is equally interest in dose escalation to the gross tumor volume where the majority of failures occur. We report our preliminary results using hypofractionated intensity-modulated accelerated radiotherapy regimen in the treatment of patients with GBM. Between July 1998 and December 2001, 25 patients with histologically proven diagnosis of GBM, Karnofsky performance status > or =60, and a postoperative tumor volume step-and-shoot technique), 60 Gy in 20 daily fractions of 3 Gy each were given to the GTV, whereas the planning target volume received a minimum of 40 Gy in 20 fractions of 2 Gy each at its periphery. Treatments were delivered over a 4-week period using 5 daily fractions per week. Dose was prescribed at the isocenter (ICRU point). Three beam angles were used in all of the cases. Treatments were well tolerated. Acute toxicity was limited to increased brain edema during radiotherapy in 2 patients who were on tapering doses of corticosteroids. This was corrected by increasing the steroid dose. At a median follow-up of 8.8 months, no late toxicity was observed. One patient experienced visual loss at 9 months after completion of treatment. MRI suggested nonspecific changes to the optic chiasm. On review of the treatment plan, the total dose to the optic chiasm was confirmed to be equal to or less than 40 Gy in 20 fractions. When Radiation Therapy Oncology Group recursive partitioning analysis was used, 10 patients were class III-IV, and 15 patients were class V-VI. To date, 21 patients have had clinical and/or radiologic evidence of disease progression, and 16 patients have died. The median survival was 9.5 months (range: 2.8-22.9 months), the 1-year survival

  1. Acute and Late Toxicity in a Randomized Trial of Conventional Versus Hypofractionated Three-Dimensional Conformal Radiotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Arcangeli, Giorgio; Fowler, Jack; Gomellini, Sara; Arcangeli, Stefano; Saracino, Biancamaria; Petrongari, Maria Grazia; Benassi, Marcello; Strigari, Lidia

    2011-01-01

    Purpose: To compare the toxicity between hypofractionation vs. conventional fractionation schedules in patients with high-risk prostate cancer. Methods and Materials: Between January 2003 and December 2007, 168 patients were randomized to receive either hypofractionated (62 Gy in 20 fractions within 5 weeks, 4 fractions/wk) or conventionally fractionated (80 Gy in 40 fractions within 8 weeks) three-dimensional conformal radiotherapy to the prostate and seminal vesicles. All patients had undergone a 9-month course of total androgen deprivation, with radiotherapy starting 2 months after initiation of the total androgen deprivation. Results: The median follow-up was 32 and 35 months in the hypofractionation and conventional fractionation arms, respectively. For the patients developing acute toxicity, no difference between the two fractionation groups was found in either severity or duration of gastrointestinal or genitourinary toxicity. Also, no difference was found in the incidence and severity of late gastrointestinal and genitourinary toxicity between the two treatment schedules, with a 3-year rate of Grade 2 or greater toxicity of 17% and 16% for the hypofractionation arm and 14% and 11% for the conventional fractionation arm, respectively. A statistically significant correlation between acute and late gastrointestinal toxicity was found only in the conventional fractionation group. Conclusion: Our findings suggest that the hypofractionation regimen used in our study is safe, with only a slight, nonsignificant increase in tolerable and temporary acute toxicity compared with the conventional fractionation schedule. The severity and frequency of late complications was equivalent between the two treatment groups.

  2. Modeling Local Control After Hypofractionated Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer: A Report From the Elekta Collaborative Lung Research Group

    International Nuclear Information System (INIS)

    Ohri, Nitin; Werner-Wasik, Maria; Grills, Inga S.; Belderbos, José; Hope, Andrew; Yan Di; Kestin, Larry L.; Guckenberger, Matthias; Sonke, Jan-Jakob; Bissonnette, Jean-Pierre; Xiao, Ying

    2012-01-01

    Purpose: Hypofractionated stereotactic body radiation therapy (SBRT) has emerged as an effective treatment option for early-stage non-small cell lung cancer (NSCLC). Using data collected by the Elekta Lung Research Group, we generated a tumor control probability (TCP) model that predicts 2-year local control after SBRT as a function of biologically effective dose (BED) and tumor size. Methods and Materials: We formulated our TCP model as follows: TCP = e [BED10−c∗L−TCD50]/k ÷ (1 + e [BED10−c∗L−TCD50]/k ), where BED10 is the biologically effective SBRT dose, c is a constant, L is the maximal tumor diameter, and TCD50 and k are parameters that define the shape of the TCP curve. Least-squares optimization with a bootstrap resampling approach was used to identify the values of c, TCD50, and k that provided the best fit with observed actuarial 2-year local control rates. Results: Data from 504 NSCLC tumors treated with a variety of SBRT schedules were available. The mean follow-up time was 18.4 months, and 26 local recurrences were observed. The optimal values for c, TCD50, and k were 10 Gy/cm, 0 Gy, and 31 Gy, respectively. Thus, size-adjusted BED (sBED) may be defined as BED minus 10 times the tumor diameter (in centimeters). Our TCP model indicates that sBED values of 44 Gy, 69 Gy, and 93 Gy provide 80%, 90%, and 95% chances of tumor control at 2 years, respectively. When patients were grouped by sBED, the model accurately characterized the relationship between sBED and actuarial 2-year local control (r=0.847, P=.008). Conclusion: We have developed a TCP model that predicts 2-year local control rate after hypofractionated SBRT for early-stage NSCLC as a function of biologically effective dose and tumor diameter. Further testing of this model with additional datasets is warranted.

  3. Modeling Local Control After Hypofractionated Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer: A Report From the Elekta Collaborative Lung Research Group

    Energy Technology Data Exchange (ETDEWEB)

    Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Werner-Wasik, Maria [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Grills, Inga S. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Belderbos, Jose [Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam (Netherlands); Hope, Andrew [Department of Radiation Oncology, Princess Margaret Hospital and University of Toronto, Toronto, ON (Canada); Yan Di; Kestin, Larry L. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Guckenberger, Matthias [Department of Radiation Oncology, University of Wuerzburg, Wuerzburg (Germany); Sonke, Jan-Jakob [Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam (Netherlands); Bissonnette, Jean-Pierre [Department of Radiation Oncology, Princess Margaret Hospital and University of Toronto, Toronto, ON (Canada); Xiao, Ying [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2012-11-01

    Purpose: Hypofractionated stereotactic body radiation therapy (SBRT) has emerged as an effective treatment option for early-stage non-small cell lung cancer (NSCLC). Using data collected by the Elekta Lung Research Group, we generated a tumor control probability (TCP) model that predicts 2-year local control after SBRT as a function of biologically effective dose (BED) and tumor size. Methods and Materials: We formulated our TCP model as follows: TCP = e{sup [BED10-c Asterisk-Operator L-TCD50]/k} Division-Sign (1 + e{sup [BED10-c Asterisk-Operator L-TCD50]/k}), where BED10 is the biologically effective SBRT dose, c is a constant, L is the maximal tumor diameter, and TCD50 and k are parameters that define the shape of the TCP curve. Least-squares optimization with a bootstrap resampling approach was used to identify the values of c, TCD50, and k that provided the best fit with observed actuarial 2-year local control rates. Results: Data from 504 NSCLC tumors treated with a variety of SBRT schedules were available. The mean follow-up time was 18.4 months, and 26 local recurrences were observed. The optimal values for c, TCD50, and k were 10 Gy/cm, 0 Gy, and 31 Gy, respectively. Thus, size-adjusted BED (sBED) may be defined as BED minus 10 times the tumor diameter (in centimeters). Our TCP model indicates that sBED values of 44 Gy, 69 Gy, and 93 Gy provide 80%, 90%, and 95% chances of tumor control at 2 years, respectively. When patients were grouped by sBED, the model accurately characterized the relationship between sBED and actuarial 2-year local control (r=0.847, P=.008). Conclusion: We have developed a TCP model that predicts 2-year local control rate after hypofractionated SBRT for early-stage NSCLC as a function of biologically effective dose and tumor diameter. Further testing of this model with additional datasets is warranted.

  4. Radiation-induced centers in inorganic glasses

    International Nuclear Information System (INIS)

    Brekhovskikh, S.M.; Tyul'nin, V.A.

    1988-01-01

    The nature, structure and formation mechanisms of radiation-induced colour centers, EPR, luminescence, generated ionizing radiation in nonorganic oxide glasses are considered. Experimental material covering both fundamental aspects of radiation physics and glass chemistry, and aspects intimately connected with the creation of new materials with the given radiation-spectral characteristics, with possibilities to prepare radiation-stable and radiation-sensitive glasses is systematized and generalized. Considerable attention is paid to the detection of radiation-induced center binding with composition, glass structures redox conditions for their synthesis. Some new possibilities of practical application of glasses with radiation-induced centers, in particular, to record optical information are reflected in the paper

  5. Integral Dose and Radiation-Induced Secondary Malignancies: Comparison between Stereotactic Body Radiation Therapy and Three-Dimensional Conformal Radiotherapy

    Directory of Open Access Journals (Sweden)

    Stefano G. Masciullo

    2012-11-01

    Full Text Available The aim of the present paper is to compare the integral dose received by non-tumor tissue (NTID in stereotactic body radiation therapy (SBRT with modified LINAC with that received by three-dimensional conformal radiotherapy (3D-CRT, estimating possible correlations between NTID and radiation-induced secondary malignancy risk. Eight patients with intrathoracic lesions were treated with SBRT, 23 Gy × 1 fraction. All patients were then replanned for 3D-CRT, maintaining the same target coverage and applying a dose scheme of 2 Gy × 32 fractions. The dose equivalence between the different treatment modalities was achieved assuming α/β = 10Gy for tumor tissue and imposing the same biological effective dose (BED on the target (BED = 76Gy10. Total NTIDs for both techniques was calculated considering α/β = 3Gy for healthy tissue. Excess absolute cancer risk (EAR was calculated for various organs using a mechanistic model that includes fractionation effects. A paired two-tailed Student t-test was performed to determine statistically significant differences between the data (p ≤ 0.05. Our study indicates that despite the fact that for all patients integral dose is higher for SBRT treatments than 3D-CRT (p = 0.002, secondary cancer risk associated to SBRT patients is significantly smaller than that calculated for 3D-CRT (p = 0.001. This suggests that integral dose is not a good estimator for quantifying cancer induction. Indeed, for the model and parameters used, hypofractionated radiotherapy has the potential for secondary cancer reduction. The development of reliable secondary cancer risk models seems to be a key issue in fractionated radiotherapy. Further assessments of integral doses received with 3D-CRT and other special techniques are also strongly encouraged.

  6. Radiation-induced camptocormia and dropped head syndrome. Review and case report of radiation-induced movement disorders

    International Nuclear Information System (INIS)

    Seidel, Clemens; Kuhnt, Thomas; Kortmann, Rolf-Dieter; Hering, Kathrin

    2015-01-01

    In recent years, camptocormia and dropped head syndrome (DHS) have gained attention as particular forms of movement disorders. Camptocormia presents with involuntary forward flexion of the thoracolumbar spine that typically increases during walking or standing and may severely impede walking ability. DHS is characterized by weakness of the neck extensors and a consecutive inability to extend the neck; in severe cases the head is fixed in a ''chin to chest position.'' Many diseases may underlie these conditions, and there have been some reports about radiation-induced camptocormia and DHS. A PubMed search with the keywords ''camptocormia,'' ''dropped head syndrome,'' ''radiation-induced myopathy,'' ''radiation-induced neuropathy,'' and ''radiation-induced movement disorder'' was carried out to better characterize radiation-induced movement disorders and the radiation techniques involved. In addition, the case of a patient developing camptocormia 23 years after radiation therapy of a non-Hodgkin's lymphoma of the abdomen is described. In total, nine case series of radiation-induced DHS (n = 45 patients) and - including our case - three case reports (n = 3 patients) about radiogenic camptocormia were retrieved. Most cases (40/45 patients) occurred less than 15 years after radiotherapy involving extended fields for Hodgkin's disease. The use of wide radiation fields including many spinal segments with paraspinal muscles may lead to radiation-induced movement disorders. If paraspinal muscles and the thoracolumbar spine are involved, the clinical presentation can be that of camptocormia. DHS may result if there is involvement of the cervical spine. To prevent these disorders, sparing of the spine and paraspinal muscles is desirable. (orig.) [de

  7. Contribution of radiation-induced, nitric oxide-mediated bystander effect to radiation-induced adaptive response.

    Science.gov (United States)

    Matsumoto, H.; Ohnishi, T.

    There has been a recent upsurge of interest in radiation-induced adaptive response and bystander effect which are specific modes in stress response to low-dose low-dose rate radiation Recently we found that the accumulation of inducible nitric oxide NO synthase iNOS in wt p53 cells was induced by chronic irradiation with gamma rays followed by acute irradiation with X-rays but not by each one resulting in an increase in nitrite concentrations of medium It is suggested that the accumulation of iNOS may be due to the depression of acute irradiation-induced p53 functions by pre-chronic irradiation In addition we found that the radiosensitivity of wt p53 cells against acute irradiation with X-rays was reduced after chronic irradiation with gamma rays This reduction of radiosensitivity of wt p53 cells was nearly completely suppressed by the addition of NO scavenger carboxy-PTIO to the medium This reduction of radiosensitivity of wt p53 cells is just radiation-induced adaptive response suggesting that NO-mediated bystander effect may considerably contribute to adaptive response induced by radiation

  8. Radiation-induced instability of human genome

    International Nuclear Information System (INIS)

    Ryabchenko, N.N.; Demina, Eh.A.

    2014-01-01

    A brief review is dedicated to the phenomenon of radiation-induced genomic instability where the increased level of genomic changes in the offspring of irradiated cells is characteristic. Particular attention is paid to the problems of genomic instability induced by the low-dose radiation, role of the bystander effect in formation of radiation-induced instability, and its relationship with individual radiosensitivity. We believe that in accordance with the paradigm of modern radiobiology the increased human individual radiosensitivity can be formed due to the genome instability onset and is a significant risk factor for radiation-induced cancer

  9. Motion-Compensated Estimation of Delivered Dose during External BeamRadiation Therapy: Implementation in Philips’ Pinnacle3 Treatment Planning System

    NARCIS (Netherlands)

    Bharat, S.; Parikh, P.; Noel, C.; Meltsner, M.; Bzdusek, K.; Kaus, M.

    2012-01-01

    Purpose: Recent research efforts investigating dose escalation techniques for three-dimensional conformal radiation therapy (3D CRT) andintensity modulated radiation therapy (IMRT) have demonstrated great benefit when high-dose hypofractionated treatment schemes are implemented16,21. The use of

  10. Hypofractionated Stereotactic Radiosurgery in a Large Bilateral Thalamic and Basal Ganglia Arteriovenous Malformation

    Directory of Open Access Journals (Sweden)

    Janet Lee

    2013-01-01

    Full Text Available Purpose. Arteriovenous malformations (AVMs in the basal ganglia and thalamus have a more aggressive natural history with a higher morbidity and mortality than AVMs in other locations. Optimal treatment—complete obliteration without new neurological deficits—is often challenging. We present a patient with a large bilateral basal ganglia and thalamic AVM successfully treated with hypofractionated stereotactic radiosurgery (HFSRS with intensity modulated radiotherapy (IMRT. Methods. The patient was treated with hypofractionated stereotactic radiosurgery to 30 Gy at margin in 5 fractions of 9 static fields with a minimultileaf collimator and intensity modulated radiotherapy. Results. At 10 months following treatment, digital subtraction angiography showed complete obliteration of the AVM. Conclusions. Large bilateral thalamic and basal ganglia AVMs can be successfully treated with complete obliteration by HFSRS with IMRT with relatively limited toxicity. Appropriate caution is recommended.

  11. Acute toxicity profile in prostate cancer with conventional and hypofractionated treatment

    International Nuclear Information System (INIS)

    Viani, Gustavo Arruda; Zulliani, Giseli Correa; Stefano, Eduardo Jose; Silva, Lucas Bernardes Godoy da; Silva, Bruna Bueno da; Crempe, Yuri Bonicelli; Martins, Vinicius Spazzapan; Ferrari, Ricardo Jose Rambaiolo; Pólo, Mariana Colbachini; Rossi, Bruno Thiago; Suguikawa, Elton

    2013-01-01

    To compare the acute toxicities in radical treatment of prostate cancer between conventional schedule (C-ARM) with 78 Gy/39 fractions and hypofractionation conformal treatment (H-ARM) with 69 Gy/23 fractions. This prospective double arm study consisted of 217 patients with prostate cancer, 112 in H-ARM and 105 in C-ARM arm. C-ARM received conventional six- field conformal radiotherapy with 78 Gy in 39 fractions while H-ARM received hypofractionation with 69 Gy in 23 fractions. Weekly assessment of acute reactions was done during treatment and with one, and 3 months using RTOG scale. Univariated analysis was performed to evaluate differences between the incidences of acute reaction in the treatment arms. Variables with p value less than 0.1 were included in the multivariated logistic regression. There was no difference between H-ARM versus C-ARM for severity and incidence in genitourinary (GU) and gastrointestinal (GI) acute toxicity. During the treatment comparing H-ARM with C-ARM no differences was observed for GI toxicity (grade 0–3; H-ARM = 45.5%, 34%, 18.7% and 1.8% versus C-ARM = 47.6%, 35.2%, 17.2% and 0). For acute GU toxicity no difference was detected between H-ARM (grade 0–3; 22.3%, 54.5%, 18.7% and 4.5%) and C-ARM (grade 0–3; 25.8%, 53.3%, 17.1% and 3.8%). At the 3- months follow-up, persistent Grade > =2 acute GU and GI toxicity were 2.5% and 1.8% in H-ARM versus 5.7% and 3% in C-ARM (p > 0.05). In univariated and multivariated analyses, there was not any dosimetric predictor for GI and GU toxicity. Our data demonstrate that hypofractionated radiotherapy achieving high biological effective dose using conformal radiotherapy is feasible for prostate cancer, being well tolerated with minimal severe acute toxicity

  12. Later Outcomes and Alpha/Beta Estimate From Hypofractionated Conformal Three-Dimensional Radiotherapy Versus Standard Fractionation for Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Leborgne, Felix [Department of Radiation Oncology, Hospital Italiano, Montevideo (Uruguay); Fowler, Jack, E-mail: jackfowlersbox@gmail.com [Department of Human Oncology, University of Wisconsin Medical School, Madison, WI (United States); Leborgne, Jose H.; Mezzera, Julieta [Department of Radiation Oncology, Hospital Italiano, Montevideo (Uruguay)

    2012-03-01

    Purpose: Now that the follow-up time has exceeded 5 years, an estimate of the {alpha}/{beta} ratio can be presented. The additional late outcomes in patients treated with three-dimensional conformal external beam radiotherapy for localized prostate cancer using a hypofractionated vs. a standard fractionation regimen are reported from this prospective nonrandomized contemporary comparison. Methods and Materials: A total of 114 nonrandomized patients chose hypofractionation delivered in 20 fractions of 3 Gy or 3.15 Gy (mean 3.06 Gy) for localized prostate cancer within a median overall time of 32 days (range, 29-49) using four fractions weekly. A total of 160 comparable patients were contemporarily treated within a median of 55 days (range 49-66). The median follow-up was 66 months (range, 24-95) for the hypofractionated arm and 63 months (range, 36-92) for the standard arm. The percentage of patients in the low-, medium-, and high-risk groups was 36%, 46%, and 18% in the hypofractionated arm and 44%, 50%, and 6% in standard arm (2 Gy), respectively. Results: The 5-year actuarial biochemical absence of disease (prostate-specific antigen nadir + 2 ng/mL) and disease-free survival rate was the same at 89% in both arms, making the {alpha}/{beta} calculation unambiguous. The point ratio of {alpha}/{beta} was 1.86 (95% confidence interval, 0.7-5.1 Gy). The 95% confidence interval was determined entirely by the binomial confidence limits in the numbers of patients. Rectal reactions of grade 3 and 4 occurred in 1 of 114 (hypofractionated) and 2 of 160 (standard) patients. Conclusions: The presented three-dimensional conformal regimen was acceptable, and the {alpha}/{beta} value was 1.8, in agreement with other very recent low meta-analyses (reviewed in the '' section).

  13. Patient costs associated with external beam radiotherapy treatment for localized prostate cancer: the benefits of hypofractionated over conventionally fractionated radiotherapy.

    Science.gov (United States)

    Sethukavalan, Perakaa; Cheung, Patrick; Tang, Colin I; Quon, Harvey; Morton, Gerard; Nam, Robert; Loblaw, Andrew

    2012-04-01

    To estimate the out-of-pocket costs for patients undergoing external beam radiotherapy (EBRT) for prostate cancer and calculate the patient-related savings of being treated with a 5-fraction versus a standard 39-fraction approach. Seventy patients accrued to the pHART3 (n = 84) study were analyzed for out-of-pocket patient costs as a result of undergoing treatment. All costs are in Canadian dollars. Using the postal code of the patient's residence, the distance between the hospital and patient home was found using Google Maps. The Canada Revenue Agency automobile allowance rate was then applied to determine the cost per kilometer driven. The average cost of travel from the hospital and pHART3 patient's residence was $246 per person after five trips. In a standard fractionation regimen, pHART3 patients would have incurred an average cost of $1921 after 39 visits. The patients receiving hypofractionated radiotherapy would have paid an average of $38 in parking while those receiving conventional treatment would have paid $293. The difference in out-of-pocket costs for the patients receiving a standard versus hypofractionated treatment was $1930. Medium term prospective data shows that hypofractionated radiotherapy is an effective treatment method for localized prostate cancer. Compared to standard EBRT, hypofractionated radiotherapy requires significantly fewer visits. Due to the long distance patients may have to travel to the cancer center and the expense of parking, the short course treatment saves each patient an average of $1900. A randomized study of standard versus hypofractionated accelerated radiotherapy should be conducted to confirm a favorable efficacy and tolerability profile of the shorter fractionation scheme.

  14. Radiation-induced heart injury

    International Nuclear Information System (INIS)

    Suzuki, Yoshihiko; Niibe, Hideo

    1975-01-01

    In order to identify radiation-induced heart injury and to differentiate it from heart disease, an attempt was made to clarify post-irradiation heart injury by investigating the histological changes which occur during the internal between the irradiation and the time of demonstrable histological changes. A study was made of 83 autopsies in which most of the primary neoplasms were breast cancers, lung cancers and mediastinal tumors. In 43 of these autopsies the heart had been irradiated. Sixty eight dd-strain mice were also used for microautoradiographic study. Histological changes in the heart were observed in 27 of the 43 cases receiving irradiation. The limit of the tolerance dose to the heart for indicating histological changes was 1220 ret in humans. The latent period without histological changes was 2.7 months after initiation of radiation therapy. Greater heart injury was observed after re-irradiation or after the combined therapy of radiation and chemotherapy especially mitomycin (MMC). The histological findings after treatment with MMC were similar to those of radiation-induced heart injury. Results of the study indicate that the damage is secondary to radiation-induced changes of the vascula connective tissue. (Evans, G.)

  15. Ion Prostate Irradiation (IPI) – a pilot study to establish the safety and feasibility of primary hypofractionated irradiation of the prostate with protons and carbon ions in a raster scan technique

    International Nuclear Information System (INIS)

    Habl, Gregor; Herfarth, Klaus; Hatiboglu, Gencay; Edler, Lutz; Uhl, Matthias; Krause, Sonja; Roethke, Matthias; Schlemmer, Heinz P; Hadaschik, Boris; Debus, Juergen

    2014-01-01

    Due to physical characteristics, ions like protons or carbon ions can administer the dose to the target volume more efficiently than photons since the dose can be lowered at the surrounding normal tissue. Radiation biological considerations are based on the assumption that the α/β value for prostate cancer cells is 1.5 Gy, so that a biologically more effective dose could be administered due to hypofractionation without increasing risks of late effects of bladder (α/β = 4.0) and rectum (α/β = 3.9). The IPI study is a prospective randomized phase II study exploring the safety and feasibility of primary hypofractionated irradiation of the prostate with protons and carbon ions in a raster scan technique. The study is designed to enroll 92 patients with localized prostate cancer. Primary aim is the assessment of the safety and feasibility of the study treatment on the basis of incidence grade III and IV NCI-CTC-AE (v. 4.02) toxicity and/or the dropout of the patient from the planned therapy due to any reason. Secondary endpoints are PSA-progression free survival (PSA-PFS), overall survival (OS) and quality-of-life (QoL). This pilot study aims at the evaluation of the safety and feasibility of hypofractionated irradiation of the prostate with protons and carbon ions in prostate cancer patients in an active beam technique. Additionally, the safety results will be compared with Japanese results recently published for carbon ion irradiation. Due to the missing data of protons in this hypofractionated scheme, an in depth evaluation of the toxicity will be created to gain basic data for a following comparison study with carbon ion irradiation. Clinical Trial Identifier: http://clinicaltrials.gov/show/NCT01641185 (clinicaltrials.gov)

  16. Radiation-induced gene expression in human subcutaneous fibroblasts is predictive of radiation-induced fibrosis

    DEFF Research Database (Denmark)

    Rødningen, Olaug Kristin; Børresen-Dale, Anne-Lise; Alsner, Jan

    2008-01-01

    BACKGROUND AND PURPOSE: Breast cancer patients show a large variation in normal tissue reactions after ionizing radiation (IR) therapy. One of the most common long-term adverse effects of ionizing radiotherapy is radiation-induced fibrosis (RIF), and several attempts have been made over the last...... years to develop predictive assays for RIF. Our aim was to identify basal and radiation-induced transcriptional profiles in fibroblasts from breast cancer patients that might be related to the individual risk of RIF in these patients. MATERIALS AND METHODS: Fibroblast cell lines from 31 individuals......-treated fibroblasts. Transcriptional differences in basal and radiation-induced gene expression profiles were investigated using 15K cDNA microarrays, and results analyzed by both SAM and PAM. RESULTS: Sixty differentially expressed genes were identified by applying SAM on 10 patients with the highest risk of RIF...

  17. Application of radiation-induced apoptosis in radiation oncology and radiation protection

    International Nuclear Information System (INIS)

    Crompton, N.E.A.; Emery, G.C.; Ozsahin, M.; Menz, R.; Knesplova, L.; Larsson, B.

    1997-01-01

    A rapid assay of the ability of lymphocytes to respond to radiation-induced damage is presented. Age and genetic dependence of radiation response have been quantified. The assay is sensitive to low doses of radiation. Its ability to assess the cytotoxic response of blood capillaries to radiation has been evaluated. (author)

  18. Radiation-induced pneumothorax

    International Nuclear Information System (INIS)

    Epstein, D.M.; Littman, P.; Gefter, W.B.; Miller, W.T.; Raney, R.B. Jr.

    1983-01-01

    Pneumothorax is an uncommon complication of radiation therapy to the chest. The proposed pathogenesis is radiation-induced fibrosis promoting subpleural bleb formation that ruptures resulting in pneumothorax. We report on two young patients with primary sarcomas without pulmonary metastases who developed spontaneous pneumothorax after irradiation. Neither patient had antecedent radiographic evidence of pulmonary fibrosis

  19. Radiation induced sarcomas of bone following therapeutic radiation

    International Nuclear Information System (INIS)

    Kim, J.H.; Chu, F.C.H.; Woodward, H.Q.; Huvos, A.

    1983-01-01

    Because of new therapeutic trends of multi-modality and the importance of late effects, we have updated our series of radiation induced bone sarcomas seen at Memorial Sloan-Kettering Cancer Center over the past four decades. A total of 37 cases of bone sarcoma arising from normal bone in the irradiated field was analyzed. The median for latent period from irradiation to diagnosis of bone sarcoma was 11 years with a minimum latent period of four years. The median radiation dose for the bone sarcoma was 6000 rad in 6 weeks with a minimum total radiation dose of 3000 rad in 3 weeks. We have found nine patients who developed bone sarcomas in the radiation field after successful treatment of Hodgkin's disease. Criteria for radiation induced bone sarcomas and the magnitude of the risk of bone sarcomas are briefly discussed

  20. Hypofractionated passively scattered proton radiotherapy for low- and intermediate-risk prostate cancer is not associated with post-treatment testosterone suppression

    Energy Technology Data Exchange (ETDEWEB)

    Kil, Whoon Jong; Nichols, Romaine C. Jr. [Dept. of Radiation Oncology, Univ. of Florida, Gainesville (United States); Univ. of Florida Proton Therapy Inst., Jacksonville (United States)], e-mail: rnichols@floridaproton.org; And others

    2013-04-15

    Background: To investigate post-treatment changes in serum testosterone in low- and intermediate-risk prostate cancer patients treated with hypofractionated passively scattered proton radiotherapy. Material and methods: Between April 2008 and October 2011, 228 patients with low- and intermediate-risk prostate cancer were enrolled into an institutional review board-approved prospective protocol. Patients received doses ranging from 70 Cobalt Gray Equivalent (CGE) to 72.5 CGE at 2.5 CGE per fraction using passively scattered protons. Three patients were excluded for receiving androgen deprivation therapy (n = 2) or testosterone supplementation (n = 1) before radiation. Of the remaining 226 patients, pretreatment serum testosterone levels were available for 217. Of these patients, post-treatment serum testosterone levels were available for 207 in the final week of treatment, 165 at the six-month follow-up, and 116 at the 12-month follow-up. The post-treatment testosterone levels were compared with the pretreatment levels using Wilcoxon's signed-rank test for matched pairs. Results: The median pretreatment serum testosterone level was 367.7 ng/dl (12.8 nmol/l). The median changes in post-treatment testosterone value were as follows: +3.0 ng/dl (+0.1 nmol/l) at treatment completion; +6.0 ng/dl (+0.2 nmol/l) at six months after treatment; and +5.0 ng/dl (0.2 nmol/l) at 12 months after treatment. None of these changes were statistically significant. Conclusion: Patients with low- and intermediate-risk prostate cancer treated with hypofractionated passively scattered proton radiotherapy do not experience testosterone suppression. Our findings are consistent with physical measurements demonstrating that proton radiotherapy is associated with less scatter radiation exposure to tissues beyond the beam paths compared with intensity-modulated photon radiotherapy.

  1. Radiation-induced bone neoplasma in facial cranium

    Energy Technology Data Exchange (ETDEWEB)

    Zomer-Drozda, J; Buraczewska-Lipinska, H; Buraczewski, J [Instytut Onkologii, Warsaw (Poland)

    1976-01-01

    Radiation-induced bone neoplasms in the region of facial cranium account for about 40% of all radiation-induced tumours of bones, although the number of cases with lesions irradiated in this area is proportionally much lower than the number of cases treated with radiotherapy in other parts of the body. Four personal cases of radiation-induced tumours with complicated course are reported. Attention is called to the value of radiological investigations in the diagnosis of bone diseases and in differential diagnosis of radiation-induced tumours of bones.

  2. Regulation of radiation-induced protein kinase Cδ activation in radiation-induced apoptosis differs between radiosensitive and radioresistant mouse thymic lymphoma cell lines

    International Nuclear Information System (INIS)

    Nakajima, Tetsuo; Yukawa, Osami; Tsuji, Hideo; Ohyama, Harumi; Wang, Bing; Tatsumi, Kouichi; Hayata, Isamu; Hama-Inaba, Hiroko

    2006-01-01

    Protein kinase Cδ (PKCδ) has an important role in radiation-induced apoptosis. The expression and function of PKCδ in radiation-induced apoptosis were assessed in a radiation-sensitive mouse thymic lymphoma cell line, 3SBH5, and its radioresistant variant, XR223. Rottlerin, a PKCδ-specific inhibitor, completely abolished radiation-induced apoptosis in 3SBH5. Radiation-induced PKCδ activation correlated with the degradation of PKCδ, indicating that PKCδ activation through degradation is involved in radiation-induced apoptosis in radiosensitive 3SBH5. In radioresistant XR223, radiation-induced PKCδ activation was lower than that in radiosensitive 3SBH5. Cytosol PKCδ levels in 3SBH5 decreased markedly after irradiation, while those in XR223 did not. There was no apparent change after irradiation in the membrane fractions of either cell type. In addition, basal cytosol PKCδ levels in XR223 were higher than those in 3SBH5. These results suggest that the radioresistance in XR223 to radiation-induced apoptosis is due to a difference in the regulation of radiation-induced PKCδ activation compared to that of 3SBH5. On the other hand, Atm -/- mouse thymic lymphoma cells were more radioresistant to radiation-induced apoptosis than wild-type mouse thymic lymphoma cells. Irradiated wild-type cells, but not Atm -/- cells, had decreased PKCδ levels, indicating that the Atm protein is involved in radiation-induced apoptosis through the induction of PKCδ degradation. The decreased Atm protein levels induced by treatment with Atm small interfering RNA had no effect on radiation-induced apoptosis in 3SBH5 cells. These results suggest that the regulation of radiation-induced PKCδ activation, which is distinct from the Atm-mediated cascade, determines radiation sensitivity in radiosensitive 3SBH5 cells

  3. 3 cases of radiation-induced sarcoma

    International Nuclear Information System (INIS)

    Shiba, Keiichiro; Fukuma, Hisatoshi; Beppu, Yasuo; Hirota, Teruyuki; Shinohara, Norio.

    1982-01-01

    Criteria for the diagnosis of radiation-induced sarcoma have been previously described. All cases must have a history of irradiation and the second neoplasm must have arisen in the area of the radiation field. A latent period of several years must have elapsed after irradiation before clinical evidence of a second malignant neoplasm. Most important thing is that, all suspected cases must have been proved histologically. We have experienced 3 cases of radiation-induced sarcoma, they were 42-years-old man who developed an osteosarcoma of the lumbar spine at the field of postoperative irradiation for seminoma 7 years previously, 69-years-old woman who developed a malignant fibrous histiocytoma of the buttock at the field of radical radiation for uterine carcinoma 7 years previously and 59-years-old woman who developed an extraskeletal osteosarcoma of the abdominal wall at the field of postoperative irradiation for uterine sarcoma 7 years previously. The last case is very rare and only 8 cases of radiation-induced extraskeletal osteosarcoma have been reported. Since there has been a definite trend in the treatment of cancer toward employing radiation for more favorable cases, in addition to technical improvements in the administration of radiotherapy and more modern equipment, survival data may have been altered considerably in many malignant tumors. Accordingly, more radiation-induced tumors may be encountered in the future. The clinical presentation and histopathology of these radiation-induced sarcomas are presented with a review of the literature. (author)

  4. Hypofractionated image guided radiation therapy followed by prostate seed implant boost for men with newly diagnosed intermediate and high risk adenocarcinoma of the prostate: Preliminary results of a phase 2 prospective study

    Directory of Open Access Journals (Sweden)

    Steven Gresswell, MD

    2016-10-01

    Conclusions: Early results on the toxicity and efficacy of the combination of hypofractionated IG-IMRT and low-dose-rate brachytherapy boost are favorable. Longer follow-up is needed to confirm safety and effectiveness.

  5. WE-FG-BRA-03: Oxygen Interplay in Hypofractionated Radiotherapy: A Hidden Opportunity

    Energy Technology Data Exchange (ETDEWEB)

    Kissick, M; Campos, D; Desai, V; Che Fru, L [University of Wisconsin Madison, Madison, WI (United States)

    2016-06-15

    Purpose: Local oxygen during a radiotherapy fraction has been shown to change over a full range of the oxygen enhancement ratio (OER) during the same time scale as the treatment fraction. Interplay with local oxygen is then likely a concern, especially for hypofractionation. Our experiments that show a strong role for metabolic dynamics suggesting one could manipulate this interplay for more efficacious treatments. Methods: Two published experiments are presented with the same human head and neck cancer cell line (UM-SCC-22B). One is a cell-specific in vitro prompt response to a 10 Gy dose of orthovotage radiation using fluorescence lifetime imaging (FLIM), benchmarked with a Seahorse assay. The other in vivo study uses autocorrelation analysis with blood oxygen level dependent magnetic resonance imaging (MRI-BOLD) on xenografts. In vivo results are verified with diffuse optics using spectra fitting and photoacoustic measurements. All these measurements are at high time resolution: sampling is one per minute. Results: Interplay happens when the radiosensitivity modulates at the same time scale as the radiation. These results show dynamics at these time scales. 1. The dominant time scale of the acute hypoxia in cell line xenografts is shown to be on the order of minutes to tens of minutes: similar to a metabolic oscillation known as the ‘glycolytic oscillator.’ 2. The radiation dose itself alters metabolism within minutes to tens of minutes also. Conclusion: These results vary with cell type. There is a possibility that special timing and dose levels could be used for radiation. Gating could be used for maximal oxygen during treatment. There is an analogy to the interplay discussions with tumor motion, except that an oxygen interplay could more likely be patient-specific at a more fundamental level.

  6. WE-FG-BRA-03: Oxygen Interplay in Hypofractionated Radiotherapy: A Hidden Opportunity

    International Nuclear Information System (INIS)

    Kissick, M; Campos, D; Desai, V; Che Fru, L

    2016-01-01

    Purpose: Local oxygen during a radiotherapy fraction has been shown to change over a full range of the oxygen enhancement ratio (OER) during the same time scale as the treatment fraction. Interplay with local oxygen is then likely a concern, especially for hypofractionation. Our experiments that show a strong role for metabolic dynamics suggesting one could manipulate this interplay for more efficacious treatments. Methods: Two published experiments are presented with the same human head and neck cancer cell line (UM-SCC-22B). One is a cell-specific in vitro prompt response to a 10 Gy dose of orthovotage radiation using fluorescence lifetime imaging (FLIM), benchmarked with a Seahorse assay. The other in vivo study uses autocorrelation analysis with blood oxygen level dependent magnetic resonance imaging (MRI-BOLD) on xenografts. In vivo results are verified with diffuse optics using spectra fitting and photoacoustic measurements. All these measurements are at high time resolution: sampling is one per minute. Results: Interplay happens when the radiosensitivity modulates at the same time scale as the radiation. These results show dynamics at these time scales. 1. The dominant time scale of the acute hypoxia in cell line xenografts is shown to be on the order of minutes to tens of minutes: similar to a metabolic oscillation known as the ‘glycolytic oscillator.’ 2. The radiation dose itself alters metabolism within minutes to tens of minutes also. Conclusion: These results vary with cell type. There is a possibility that special timing and dose levels could be used for radiation. Gating could be used for maximal oxygen during treatment. There is an analogy to the interplay discussions with tumor motion, except that an oxygen interplay could more likely be patient-specific at a more fundamental level.

  7. Extracranial Facial Nerve Schwannoma Treated by Hypo-fractionated CyberKnife Radiosurgery.

    Science.gov (United States)

    Sasaki, Ayaka; Miyazaki, Shinichiro; Hori, Tomokatsu

    2016-09-21

    Facial nerve schwannoma is a rare intracranial tumor. Treatment for this benign tumor has been controversial. Here, we report a case of extracranial facial nerve schwannoma treated successfully by hypo-fractionated CyberKnife (Accuray, Sunnyvale, CA) radiosurgery and discuss the efficacy of this treatment. A 34-year-old female noticed a swelling in her right mastoid process. The lesion enlarged over a seven-month period, and she experienced facial spasm on the right side. She was diagnosed with a facial schwannoma via a magnetic resonance imaging (MRI) scan of the head and neck and was told to wait until the facial nerve palsy subsides. She was referred to our hospital for radiation therapy. We planned a fractionated CyberKnife radiosurgery for three consecutive days. After CyberKnife radiosurgery, the mass in the right parotid gradually decreased in size, and the facial nerve palsy disappeared. At her eight-month follow-up, her facial spasm had completely disappeared. There has been no recurrence and the facial nerve function has been normal. We successfully demonstrated the efficacy of CyberKnife radiosurgery as an alternative treatment that also preserves neurofunction for facial nerve schwannomas.

  8. Modelling radiation-induced cell death and tumour re-oxygenation: local versus global and instant versus delayed cell death

    International Nuclear Information System (INIS)

    Gago-Arias, Araceli; Espinoza, Ignacio; Sánchez-Nieto, Beatriz; Aguiar, Pablo; Pardo-Montero, Juan

    2016-01-01

    The resistance of hypoxic cells to radiation, due to the oxygen dependence of radiosensitivity, is well known and must be taken into account to accurately calculate the radiation induced cell death. A proper modelling of the response of tumours to radiation requires deriving the distribution of oxygen at a microscopic scale. This usually involves solving the reaction-diffusion equation in tumour voxels using a vascularization distribution model. Moreover, re-oxygenation arises during the course of radiotherapy, one reason being the increase of available oxygen caused by cell killing, which can turn hypoxic tumours into oxic. In this work we study the effect of cell death kinetics in tumour oxygenation modelling, analysing how it affects the timing of re-oxygenation, surviving fraction and tumour control. Two models of cell death are compared, an instantaneous cell killing, mimicking early apoptosis, and a delayed cell death scenario in which cells can die shortly after being damaged, as well as long after irradiation. For each of these scenarios, the decrease in oxygen consumption due to cell death can be computed globally (macroscopic voxel average) or locally (microscopic). A re-oxygenation model already used in the literature, the so called full re-oxygenation, is also considered. The impact of cell death kinetics and re-oxygenation on tumour responses is illustrated for two radiotherapy fractionation schemes: a conventional schedule, and a hypofractionated treatment. The results show large differences in the doses needed to achieve 50% tumour control for the investigated cell death models. Moreover, the models affect the tumour responses differently depending on the treatment schedule. This corroborates the complex nature of re-oxygenation, showing the need to take into account the kinetics of cell death in radiation response models. (paper)

  9. Adaptive hypofractionated gamma knife radiosurgery for a large brainstem metastasis

    DEFF Research Database (Denmark)

    Sinclair, Georges; Bartek, Jiri; Martin, Heather

    2016-01-01

    cancer in July 2011, initially treated with chemotherapy and tyrosine kinase inhibitors, developed multiple brain metastases March 2013, with subsequent whole brain radiotherapy, after which a magnetic resonance imaging (MRI) showed a significant volume regression of all brain metastases. A follow-up MRI...... adaptive hypofractionation proved to be effective to achieve tumor control while limiting local adverse reactions. This surgical modality should be considered when managing larger brain lesions in critical areas....

  10. Radiation-induced radical ions in calcium sulfite

    Science.gov (United States)

    Bogushevich, S. E.

    2006-07-01

    We have used EPR to study the effect of γ radiation on calcium sulfite. We have observed and identified the radiation-induced radical ions SO 2 - (iso) with g = 2.0055 and SO 2 - (orth-1) with g1 = 2.0093, g2 = 2.0051, g3 = 2.0020, identical to the initial and thermally induced SO 2 - respectively, SO 3 - (iso) with g = 2.0031 and SO 3 - (axial) with g⊥ = 2.0040, g∥ = 2.0023, identical to mechanically induced SO 3 - . We have established the participation of radiation-induced radical ions SO 3 - in formation of post-radiation SO 2 - .

  11. Radiation- induced aneuploidy in mammalian germ cells

    International Nuclear Information System (INIS)

    Tease, C.

    1989-01-01

    The ability of ionizing radiation to induce aneuploidy in mammalian germ cells has been investigated experimentally in the laboratory mouse using a variety of cytogenetic and genetic methods. These studies have provided unambiguous evidence of induced nondisjunction in both male and female germ cells when the effect of irradiation is screened in meiotic cells or preimplantation embryos. In contrast, however, cytogenetic analyses of post-implantation embryos and genetic assays for induced chromosome gains have not found a significant radiation effect. These apparently contradictory findings may be reconciled if (a) radiation induces tertiary rather than primary trisomy, or (b) induces embryo-lethal genetic damage, such as deletions, in addition to numerical anomalies. Either or both of these explanations may account for the apparent loss during gestation of radiation-induced trisomic embryos. Extrapolating from the information so far available, it seems unlikely that environmental exposure to low doses if low dose rate radiation will result in a detectable increase in the rate of aneuploidy in the human population. (author)

  12. Radiation-induced camptocormia and dropped head syndrome. Review and case report of radiation-induced movement disorders

    Energy Technology Data Exchange (ETDEWEB)

    Seidel, Clemens; Kuhnt, Thomas; Kortmann, Rolf-Dieter; Hering, Kathrin [Leipzig University, Department of Radiotherapy and Radiation Oncology, Leipzig (Germany)

    2015-10-15

    In recent years, camptocormia and dropped head syndrome (DHS) have gained attention as particular forms of movement disorders. Camptocormia presents with involuntary forward flexion of the thoracolumbar spine that typically increases during walking or standing and may severely impede walking ability. DHS is characterized by weakness of the neck extensors and a consecutive inability to extend the neck; in severe cases the head is fixed in a ''chin to chest position.'' Many diseases may underlie these conditions, and there have been some reports about radiation-induced camptocormia and DHS. A PubMed search with the keywords ''camptocormia,'' ''dropped head syndrome,'' ''radiation-induced myopathy,'' ''radiation-induced neuropathy,'' and ''radiation-induced movement disorder'' was carried out to better characterize radiation-induced movement disorders and the radiation techniques involved. In addition, the case of a patient developing camptocormia 23 years after radiation therapy of a non-Hodgkin's lymphoma of the abdomen is described. In total, nine case series of radiation-induced DHS (n = 45 patients) and - including our case - three case reports (n = 3 patients) about radiogenic camptocormia were retrieved. Most cases (40/45 patients) occurred less than 15 years after radiotherapy involving extended fields for Hodgkin's disease. The use of wide radiation fields including many spinal segments with paraspinal muscles may lead to radiation-induced movement disorders. If paraspinal muscles and the thoracolumbar spine are involved, the clinical presentation can be that of camptocormia. DHS may result if there is involvement of the cervical spine. To prevent these disorders, sparing of the spine and paraspinal muscles is desirable. (orig.) [German] In den letzten Jahren haben Bewegungsstoerungen von Wirbelsaeule und paraspinaler Muskulatur in

  13. Improving CT quality with optimized image parameters for radiation treatment planning and delivery guidance

    Directory of Open Access Journals (Sweden)

    Guang-Pei Chen

    2017-10-01

    Conclusion: CT image quality can be improved with the IQE protocols created in this study, to provide better soft tissue contrast, which would be beneficial for use in radiation therapy, e.g., for planning data acquisition or for IGRT for hypo-fractionated treatments.

  14. Radiation-induced myelopathy

    Energy Technology Data Exchange (ETDEWEB)

    Gaenshirt, H [Heidelberg Univ. (F.R. Germany). Neurologische Klinik

    1975-10-01

    12 cases of radiation-induced myelopathy after /sup 60/Co teletherapy are reported on. Among these were 10 thoracal lesions, one cerviothoracal lesion, and one lesion of the medulla oblongata. In 9 cases, Hodgkin's disease had been the primary disease, tow patients had been irradiated because of suspected vertebral metastases of cancer of the breast, and one patient had suffered from a glomus tumour of the petrous bone. The spinal doses had exceeded the tolerance doses recommended in the relevant literature. There was no close correlation between the radiation dose and the course of the disease. The latency periods between the end of the radiotherapy and the onset of the neurological symptons varied from 6 to 16 mouths and were very constant in 7 cases with 6 to 9 months. The segmental height of the lesion corresponded to the level of irradiation. The presenting symptons of radiation-induced myelopathy are buruing dysaesthesias and Brown-Sequard's paralysis which may develop into transverse lesion of the cord with paraplegia still accompanied by dissociated perception disorders. The disease developed intermittently. Disturbances of the bladder function are frequent. The fluid is normal in most cases. Myelographic examinations were made in 8 cases. 3 cases developed into stationary cases exhibiting. Brown-Sequard syndrome, while 9 patients developed transverse lesion of the cord with paraplegia. 3 patients have died; antopsy findings are given for two of these. In the pathogenesis of radiation-induced myelopathy, the vascular factor is assumed to be of decisive importance.

  15. Phase I Trial of Preoperative Hypofractionated Intensity-Modulated Radiotherapy with Incorporated Boost and Oral Capecitabine in Locally Advanced Rectal Cancer

    International Nuclear Information System (INIS)

    Freedman, Gary M.; Meropol, Neal J.; Sigurdson, Elin R.; Hoffman, John; Callahan, Elaine; Price, Robert; Cheng, Jonathan; Cohen, Steve; Lewis, Nancy; Watkins-Bruner, Deborah; Rogatko, Andre; Konski, Andre

    2007-01-01

    Purpose: To determine the safety and efficacy of preoperative hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) and an incorporated boost with concurrent capecitabine in patients with locally advanced rectal cancer. Methods and Materials: The eligibility criteria included adenocarcinoma of the rectum, T3-T4 and/or N1-N2 disease, performance status 0 or 1, and age ≥18 years. Photon IMRT and an incorporated boost were used to treat the whole pelvis to 45 Gy and the gross tumor volume plus 2 cm to 55 Gy in 25 treatments within 5 weeks. The study was designed to escalate the dose to the gross tumor volume in 5-Gy increments in 3-patient cohorts. Capecitabine was given orally 825 mg/m 2 twice daily for 7 days each week during RT. The primary endpoint was the maximal tolerated radiation dose, and the secondary endpoints were the pathologic response and quality of life. Results: Eight patients completed RT at the initial dose level of 55 Gy. The study was discontinued because of toxicity-six Grade 3 toxicities occurred in 3 (38%) of 8 patients. All patients went on to definitive surgical resection, and no patient had a pathologically complete response. Conclusion: This regimen, using hypofractionated RT with an incorporated boost, had unacceptable toxicity despite using standard doses of capecitabine and IMRT. Additional research is needed to determine whether IMRT is able to reduce the side effects during and after pelvic RT with conventional dose fractionation

  16. Radiation-induced genomic instability and bystander effects: related inflammatory-type responses to radiation-induced stress and injury? A review.

    Science.gov (United States)

    Lorimore, S A; Wright, E G

    2003-01-01

    To review studies of radiation responses in the haemopoietic system in the context of radiation-induced genomic instability, bystander effects and inflammatory-type processes. There is considerable evidence that cells that themselves are not exposed to ionizing radiation but are the progeny of cells irradiated many cell divisions previously may express a high frequency of gene mutations, chromosomal aberrations and cell death. These effects are collectively known as radiation-induced genomic instability. A second untargeted effect results in non-irradiated cells exhibiting responses typically associated with direct radiation exposure but occurs as a consequence of contact with irradiated cells or by receiving soluble signals from irradiated cells. These effects are collectively known as radiation-induced bystander effects. Reported effects include increases or decreases in damage-inducible and stress-related proteins; increases or decreases in reactive oxygen species, cell death or cell proliferation, and induction of mutations and chromosome aberrations. This array of responses is reminiscent of effects mediated by cytokines and other similar regulatory factors that may involve, but do not necessarily require, gap junction-mediated transfer, have multiple inducers and a variety of context-dependent consequences in different cell systems. That chromosomal instability in haemopoietic cells can be induced by an indirect bystander-type mechanism both in vitro and in vivo provides a potential link between these two untargeted effects and there are radiation responses in vivo consistent with the microenvironment contributing secondary cell damage as a consequence of an inflammatory-type response to radiation-induced injury. Intercellular signalling, production of cytokines and free radicals are features of inflammatory responses that have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. The

  17. Radiation-induced polymerization and radiation effect on polymers

    International Nuclear Information System (INIS)

    Seguchi, Tadao

    1977-12-01

    The processes of radiation-induced polymerization of monomers and also radiation effects on polymers have been studied by instrumental analyses of electron spin resonance (ESR), nuclear magnetic resonance (NMR) and electron microscopy. In radiation-induced polymerization, graft-copolymerization and absorbed state polymerization were taken up. For graft-copolymerization, monomers such as methylmethacrylate and butadiene were made to react with irradiated polyethylene, and behaviors of the initiating radicals and propagating radicals were followed under the reaction by ESR. For absorbed state polymerization, acrylonitrile/zeolite and methylmethacrylate/zeolite were chosen. Absorbed monomers were irradiated at 77 0 K and polymerized at room temperature. Active species and the concentrations were measured by ESR and the yields of polymer were observed by NMR. In radiation effect on polymers, polyvinylfluoride, polyvinylidenfluoride and polytetrafluoroethylene were taken up. Active species trapped in the polymer matrixes were identified and decay and reactivity of the species were also studied. On the basis of information from the electron microscopy and x-ray analysis, radiation effects on these polymers are described. In polytetrafluoroethylene produced by radiation polymerization, the relation between morphology and polymerization conditions and also the process of crystallization during polymerization were studied. (auth.)

  18. Study on radiation-inducible genes

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sang Yong; Kim, Dong Ho; Joe, Min Ho; Park, Hae Jun; Song, Hyu Npa

    2012-01-15

    Radiation-inducible genes of E. coli, which is a model strain for bacterial study, and Salmonella, which is a typical strain for pathogenic bacteria were compared through omic analysis. Heat shock response genes and prophage genes were induced by radiation in Salmonella, not in E. coli. Among prophage genes tested, STM2628 showed the highest activation by radiation, and approximately 1 kb promoter region was turned out to be necessary for radiation response. To screen an artificial promoter showing activation by 2 Gy, the high-throughput screening method using fluorescent MUG substrate was established. The use of bacteria as anticancer agents has attracted interest. In this study, we tried to develop tumor targeting bacteria in which the radiation-inducible promoter activate a transgene encoding a cytotoxic protein. To do this, a tumor-targeting hfq Salmonella mutant strain was constructed, and we found that its virulence decreased. For outward secretion of anticancer protein produced inside bacteria, the signal peptide of SspH1 was determined and the signal peptide was proven to be able to secrete an anticancer protein. Tumor xenograft mouse model was secured, which can be used for efficiency evaluation of bacterial tumor therapy.

  19. Study on radiation-inducible genes

    International Nuclear Information System (INIS)

    Lim, Sang Yong; Kim, Dong Ho; Joe, Min Ho; Park, Hae Jun; Song, Hyu Npa

    2012-01-01

    Radiation-inducible genes of E. coli, which is a model strain for bacterial study, and Salmonella, which is a typical strain for pathogenic bacteria were compared through omic analysis. Heat shock response genes and prophage genes were induced by radiation in Salmonella, not in E. coli. Among prophage genes tested, STM2628 showed the highest activation by radiation, and approximately 1 kb promoter region was turned out to be necessary for radiation response. To screen an artificial promoter showing activation by 2 Gy, the high-throughput screening method using fluorescent MUG substrate was established. The use of bacteria as anticancer agents has attracted interest. In this study, we tried to develop tumor targeting bacteria in which the radiation-inducible promoter activate a transgene encoding a cytotoxic protein. To do this, a tumor-targeting hfq Salmonella mutant strain was constructed, and we found that its virulence decreased. For outward secretion of anticancer protein produced inside bacteria, the signal peptide of SspH1 was determined and the signal peptide was proven to be able to secrete an anticancer protein. Tumor xenograft mouse model was secured, which can be used for efficiency evaluation of bacterial tumor therapy

  20. Radiation-induced cancers in man

    International Nuclear Information System (INIS)

    Hirose, Fumio

    1978-01-01

    Radiation-induced cancers in man were divided into three groups, a group in which cancers occurred after atomic bomb exposure, a group in which cancers occurred in radiologists and other medical specialists, and a group in which cancers occurred after exposure to diagnostic radiation, and they were summarized. In atomic bomb survivors leukemia, thyroid cancer, salivary gland cancer, lung cancer, and breast cancer occurred so frequently. In addition to them, mortality ratios by malignant lymphoma, stomach cancer, esophageal cancer, and by cancer of urinary tract were increased. The incidence of leukemia was decreased in those who treated radiation owing to the development of the protection of occupational exposure, and the incidence of radiation-induced cancers was decreased in patients owing to the improvement of therapy. However, a new problem has arisen as to the occurrence of cancers after medical exposure, such as various histological types of cancers after the treatment of skin diseases on the head, and breast cancer after the treatment of pneumothorax. Dose-to-effect relation, hereditary factors, effect of age, immunological influences and endocrine actions were also studied in each radiation-induced cancer. (Ichikawa, K.)

  1. Radiation-induced cancers in man

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, F [Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology

    1978-07-01

    Radiation-induced cancers in man were divided into three groups, a group in which cancers occurred after atomic bomb exposure, a group in which cancers occurred in radiologists and other medical specialists, and a group in which cancers occurred after exposure to diagnostic radiation, and they were summarized. In atomic bomb survivors leukemia, thyroid cancer, salivary gland cancer, lung cancer, and breast cancer occurred so frequently. In addition to them, mortality ratios by malignant lymphoma, stomach cancer, esophageal cancer, and by cancer of urinary tract were increased. The incidence of leukemia was decreased in those who treated radiation owing to the development of the protection of occupational exposure, and the incidence of radiation-induced cancers was decreased in patients owing to the improvement of therapy. However, a new problem has arisen as to the occurrence of cancers after medical exposure, such as various histological types of cancers after the treatment of skin diseases on the head, and breast cancer after the treatment of pneumothorax. Dose-to-effect relation, hereditary factors, effect of age, immunological influences and endocrine actions were also studied in each radiation-induced cancer.

  2. Radiation-induced brain injury: A review

    Directory of Open Access Journals (Sweden)

    Michael eRobbins

    2012-07-01

    Full Text Available Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (> 6 months to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses > 30 Gy; white matter necrosis occurs at fractionated doses > 60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain

  3. Image-Guided Hypofractionated Radiotherapy in Low-Risk Prostate Cancer Patients

    Directory of Open Access Journals (Sweden)

    Maurizio Valeriani

    2014-01-01

    Full Text Available Aim. To evaluate efficacy and toxicity of image-guided hypofractionated radiotherapy (HFRT in the treatment of low-risk prostate cancer. Outcomes and toxicities of this series of patients were compared to another group of 32 low-risk patients treated with conventional fractionation (CFRT. Methods. Fifty-nine patients with low-risk prostate cancer were analysed. Total dose for the prostate and proximal seminal vesicles was 60 Gy delivered in 20 fractions. Results. The median follow-up was 30 months. The actuarial 4-year overall survival, biochemical free survival, and disease specific survival were 100%, 97.4%, and 97.4%, respectively. Acute grade 1-2 gastrointestinal (GI and genitourinary (GU toxicity rates were 11.9% and 40.7%, respectively. Grade 1 GI and GU late toxicity rates were 8.5% and 13.6%, respectively. No grade ≥2 late toxicities were recorded. Acute grade 2-3 GU toxicity resulted significantly lower (P=0.04 in HFRT group compared to the CFRT group. The cumulative 4-year incidence of grade 1-2 GU toxicity was significantly higher (P<0.001 for HFRT patients. Conclusions. Our study demonstrated that hypofractionated regimen provided excellent biochemical control in favorable risk prostate cancer patients. The incidence of GI and GU toxicity was low. However, HFRT presented higher cumulative incidence of low-grade late GU toxicity than CFRT.

  4. Ionizing radiation induced malignancies in man

    International Nuclear Information System (INIS)

    Dutrillaux, B.

    1997-01-01

    Using data on gene and chromosome alterations in human cancers, it is proposed that most radiation induced cancers are a consequence of recessive mutations of tumor suppressor genes. This explains the long delay between radiation exposure and the cancer onset. As a consequence, radiation induced cancers belong to groups of tumors where no specific translocations (forming or activating oncogenes) but multiple unbalanced chromosome rearrangements (deletions unmasking recessive mutations) exist. This explains why osteosarcomas, malignant fibrous histiocytoma, chondrosarcomas are frequently induced, but not liposarcoma, Ewing sarcomas and rhabdomyosarcomas, among others. A single exception confirms this rule: papillary thyroid cancer, frequently induced in exposed children, in which structural rearrangements frequently form a RET/PTC3 fusion gene. This fusion gene is the results of the inversion of a short segment of chromosome 10, and it is assumed that such rearrangement (small para-centric inversion) can easily occur after exposure to radiations, at contrast with translocations between to genes belonging to different chromosomes. (author)

  5. Three cases of radiation-induced cancer in oral regions

    International Nuclear Information System (INIS)

    Kawamura, Hiroshi; Shinoki, Kunihiko; Endo, Yoshitaka; Fujita, Yasushi; Hayashi, Susumu

    1985-01-01

    Three cases of radiation-induced cancer in the oral regions were reported with relation to radiation therapy. One was the general radiation-induced cancer following radiotherapy for the hemangioma. The other two cases, which belonged in the B-1 group of Sakai and his coworker's diagnostic criteria for radiation-induced cancer, were those occurring after radiotherapy for the malignant tumors. Due to the relatively high dosage exposure by the patient in the radiotherapy it is necessary to look out the latency of the radiation-induced cancer. After radiotherapy, careful and periodical observation is important for immediate treatment in an early stage for the radiation-induced cancer to have a favorable prognosis. In addition careful observation of the changes after radiotherapy helps in discovering the precancerous lesions from the therapy. For the radiation-induced cancer, surgical treatment would be the best, however, radiation therapy is also effective in certain cases. (author)

  6. SNP in TXNRD2 Associated With Radiation-Induced Fibrosis: A Study of Genetic Variation in Reactive Oxygen Species Metabolism and Signaling

    International Nuclear Information System (INIS)

    Edvardsen, Hege; Landmark-Høyvik, Hege; Reinertsen, Kristin V.; Zhao, Xi; Grenaker-Alnæs, Grethe Irene; Nebdal, Daniel; Syvänen, Ann-Christine; Rødningen, Olaug; Alsner, Jan; Overgaard, Jens; Borresen-Dale, Anne-Lise; Fosså, Sophie D.; Kristensen, Vessela N.

    2013-01-01

    Purpose: The aim of the study was to identify noninvasive markers of treatment-induced side effects. Reactive oxygen species (ROS) are generated after irradiation, and genetic variation in genes related to ROS metabolism might influence the level of radiation-induced adverse effects (AEs). Methods and Materials: 92 breast cancer (BC) survivors previously treated with hypofractionated radiation therapy were assessed for the AEs subcutaneous atrophy and fibrosis, costal fractures, lung fibrosis, pleural thickening, and telangiectasias (median follow-up time 17.1 years). Single-nucleotide polymorphisms (SNPs) in 203 genes were analyzed for association to AE grade. SNPs associated with subcutaneous fibrosis were validated in an independent BC survivor material (n=283). The influence of the studied genetic variation on messenger ribonucleic acid (mRNA) expression level of 18 genes previously associated with fibrosis was assessed in fibroblast cell lines from BC patients. Results: Subcutaneous fibrosis and atrophy had the highest correlation (r=0.76) of all assessed AEs. The nonsynonymous SNP rs1139793 in TXNRD2 was associated with grade of subcutaneous fibrosis, the reference T-allele being more prevalent in the group experiencing severe levels of fibrosis. This was confirmed in another sample cohort of 283 BC survivors, and rs1139793 was found significantly associated with mRNA expression level of TXNRD2 in blood. Genetic variation in 24 ROS-related genes, including EGFR, CENPE, APEX1, and GSTP1, was associated with mRNA expression of 14 genes previously linked to fibrosis (P≤.005). Conclusion: Development of subcutaneous fibrosis can be associated with genetic variation in the mitochondrial enzyme TXNRD2, critically involved in removal of ROS, and maintenance of the intracellular redox balance

  7. The nature and principles of the radiation-induced cancerogenesis

    International Nuclear Information System (INIS)

    Lips'ka, A.YI.; Serkyiz, Ya.Yi.

    2004-01-01

    The paper represents the analysis of the authors and literary data concerning the nature and principles of the radiation-induced neoplasms. The mechanisms of the radiation-induced cancerogenesis development are not clear understood. The experimental data altogether do not allow developing the mathematical model of the radiation-induced cancerogenesis at the molecular level. This model has to take into account all necessary indices including radiation factor and the state of the organism. The general principles of the radiation-induced cancerogenesis have been formulated in the present review. It is possible to use these principles in order to predict and calculate the risks of the radiation-induced neoplasms

  8. Under-reported dosimetry errors due to interplay effects during VMAT dose delivery in extreme hypofractionated stereotactic radiotherapy.

    Science.gov (United States)

    Gauer, Tobias; Sothmann, Thilo; Blanck, Oliver; Petersen, Cordula; Werner, René

    2018-06-01

    Radiotherapy of extracranial metastases changed from normofractioned 3D CRT to extreme hypofractionated stereotactic treatment using VMAT beam techniques. Random interaction between tumour motion and dynamically changing beam parameters might result in underdosage of the CTV even for an appropriately dimensioned ITV (interplay effect). This study presents a clinical scenario of extreme hypofractionated stereotactic treatment and analyses the impact of interplay effects on CTV dose coverage. For a thoracic/abdominal phantom with an integrated high-resolution detector array placed on a 4D motion platform, dual-arc treatment plans with homogenous target coverage were created using a common VMAT technique and delivered in a single fraction. CTV underdosage through interplay effects was investigated by comparing dose measurements with and without tumour motion during plan delivery. Our study agrees with previous works that pointed out insignificant interplay effects on target coverage for very regular tumour motion patterns like simple sinusoidal motion. However, we identified and illustrated scenarios that are likely to result in a clinically relevant CTV underdosage. For tumour motion with abnormal variability, target coverage quantified by the CTV area receiving more than 98% of the prescribed dose decreased to 78% compared to 100% at static dose measurement. This study is further proof of considerable influence of interplay effects on VMAT dose delivery in stereotactic radiotherapy. For selected conditions of an exemplary scenario, interplay effects and related motion-induced target underdosage primarily occurred in tumour motion pattern with increased motion variability and VMAT plan delivery using complex MLC dose modulation.

  9. Radiation-induced linking reactions in polyethylene

    International Nuclear Information System (INIS)

    Zoepfl, F.J.

    1983-01-01

    Three types of measurements are reported relating to chemical reactions in polyethylene induced by ionizing radiation: 1) viscometric and low-angle laser light scattering measurements to determine the effect of a radical scavenger on the yield of links; 2) calorimetric measurements to determine the effect of radiation-induced linking on the melting behavior of polyethylene; and 3) high-resolution solution carbon 13 nuclear magnetic resonance (NMR) spectrometry measurements to determine the nature of the links and the method of their formation. The NMR results present the first direct detection of radiation-induced long-chain branching (Y links) in polyethylene, and place an apparent upper limit on the yield of H-shaped crosslinks that are formed when polyethylene is irradiated to low absorbed doses. The effect of radiation-induced linking on the melting behavior of polyethylene was examined using differential scanning calorimetry (DSC). It was found that radiation-induced links do not change the heat of fusion of polythylene crystals, but decrease the melt entropy and increase the fold surface free energy per unit area of the crystals. The carbon 13 NMR results demonstrate that long-chain branches (Y links) are formed much more frequently than H-shaped crosslinks at low absorbed doses. The Y links are produced by reactions of alkyl free radicals with terminal vinyl groups in polyethylene

  10. Genetic alterations during radiation-induced carcinogenesis

    International Nuclear Information System (INIS)

    Kodama, Seiji

    1995-01-01

    This paper reviews radiation-induced genetic alterations and its carcinogenesis, focusing on the previous in vitro assay outcome. A colony formation assay using Syrian hamster fetal cells and focus formation assay using mouse C3H10T1/2 cells are currently available to find malignant transformation of cells. Such in vitro assays has proposed the hypothesis that radiation-induced carcinogenesis arises from at least two-stage processes; i.e., that an early step induced by irradiation plays an important role in promoting the potential to cause the subsequent mutation. A type of genetic instability induced by radiation results in a persistently elevated frequency of spontaneous mutations, so-called the phenomenon of delayed reproductive death. One possible mechanism by which genetic instability arises has been shown to be due to the development of abnormality in the gene group involved in the maintenance mechanism of genome stability. Another possibility has also been shown to stem from the loss of telomere (the extremities of a chromosome). The importance of search for radiation-induced genetic instability is emphasized in view of the elucidation of carcinogenesis. (N.K.)

  11. Hypofractionation Regimens for Stereotactic Radiotherapy for Large Brain Tumors

    International Nuclear Information System (INIS)

    Yuan Jiankui; Wang, Jian Z.; Lo, Simon; Grecula, John C.; Ammirati, Mario; Montebello, Joseph F.; Zhang Hualin; Gupta, Nilendu; Yuh, William T.C.; Mayr, Nina A.

    2008-01-01

    Purpose: To investigate equivalent regimens for hypofractionated stereotactic radiotherapy (HSRT) for brain tumor treatment and to provide dose-escalation guidance to maximize the tumor control within the normal brain tolerance. Methods and Materials: The linear-quadratic model, including the effect of nonuniform dose distributions, was used to evaluate the HSRT regimens. The α/β ratio was estimated using the Gammaknife stereotactic radiosurgery (GKSRS) and whole-brain radiotherapy experience for large brain tumors. The HSRT regimens were derived using two methods: (1) an equivalent tumor control approach, which matches the whole-brain radiotherapy experience for many fractions and merges it with the GKSRS data for few fractions; and (2) a normal-tissue tolerance approach, which takes advantages of the dose conformity and fractionation of HSRT to approach the maximal dose tolerance of the normal brain. Results: A plausible α/β ratio of 12 Gy for brain tumor and a volume parameter n of 0.23 for normal brain were derived from the GKSRS and whole-brain radiotherapy data. The HSRT prescription regimens for the isoeffect of tumor irradiation were calculated. The normal-brain equivalent uniform dose decreased as the number of fractions increased, because of the advantage of fractionation. The regimens for potential dose escalation of HSRT within the limits of normal-brain tolerance were derived. Conclusions: The designed hypofractionated regimens could be used as a preliminary guide for HSRT dose prescription for large brain tumors to mimic the GKSRS experience and for dose escalation trials. Clinical studies are necessary to further tune the model parameters and validate these regimens

  12. A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Monjazeb, Arta M., E-mail: arta.monjazeb@ucdmc.ucdavis.edu [U.C. Davis School of Medicine, Department of Radiation Oncology, Sacramento, CA (United States); Ayala, Deandra; Jensen, Courtney [Radiation Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Case, L. Douglas [Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Bourland, J. Daniel; Ellis, Thomas L. [Neurosurgery, Wake Forest University Health Sciences, Winston-Salem, NC (United States); McMullen, Kevin P.; Chan, Michael D. [Radiation Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Tatter, Stephen B. [Neurosurgery, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Lesser, Glen J. [Hematology Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Shaw, Edward G. [Radiation Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States)

    2012-02-01

    Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4-5 acute neurotoxicity attributable to radiotherapy. Results: All patients experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.

  13. A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

    International Nuclear Information System (INIS)

    Monjazeb, Arta M.; Ayala, Deandra; Jensen, Courtney; Case, L. Douglas; Bourland, J. Daniel; Ellis, Thomas L.; McMullen, Kevin P.; Chan, Michael D.; Tatter, Stephen B.; Lesser, Glen J.; Shaw, Edward G.

    2012-01-01

    Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4–5 acute neurotoxicity attributable to radiotherapy. Results: All patients experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.

  14. Radiation-induced brain injury: A review

    Energy Technology Data Exchange (ETDEWEB)

    Greene-Schloesser, Dana; Robbins, Mike E.; Peiffer, Ann M.; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Wheeler, Kenneth T. [Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Department of Radiology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Chan, Michael D., E-mail: mrobbins@wakehealth.edu [Department of Radiation Oncology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States)

    2012-07-19

    Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their

  15. Radiation-induced brain injury: A review

    International Nuclear Information System (INIS)

    Greene-Schloesser, Dana; Robbins, Mike E.; Peiffer, Ann M.; Shaw, Edward G.; Wheeler, Kenneth T.; Chan, Michael D.

    2012-01-01

    Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their

  16. Delayed Radiation-Induced Vasculitic Leukoencephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Rauch, Philipp J. [Departments of Pathology and Neurosurgery, Yale University School of Medicine, New Haven, Connecticut (United States); Faculty of Medicine, University of Heidelberg, Heidelberg (Germany); Park, Henry S. [Departments of Pathology and Neurosurgery, Yale University School of Medicine, New Haven, Connecticut (United States); Knisely, Jonathan P.S. [Department of Radiation Medicine, North Shore University Hospital, Manhasset, New York (United States); Chiang, Veronica L. [Departments of Pathology and Neurosurgery, Yale University School of Medicine, New Haven, Connecticut (United States); Vortmeyer, Alexander O., E-mail: alexander.vortmeyer@yale.edu [Departments of Pathology and Neurosurgery, Yale University School of Medicine, New Haven, Connecticut (United States)

    2012-05-01

    Purpose: Recently, single-fraction, high-dosed focused radiation therapy such as that administered by Gamma Knife radiosurgery has been used increasingly for the treatment of metastatic brain cancer. Radiation therapy to the brain can cause delayed leukoencephalopathy, which carries its own significant morbidity and mortality. While radiosurgery-induced leukoencephalopathy is known to be clinically different from that following fractionated radiation, pathological differences are not well characterized. In this study, we aimed to integrate novel radiographic and histopathologic observations to gain a conceptual understanding of radiosurgery-induced leukoencephalopathy. Methods and Materials: We examined resected tissues of 10 patients treated at Yale New Haven Hospital between January 1, 2009, and June 30, 2010, for brain metastases that had been previously treated with Gamma Knife radiosurgery, who subsequently required surgical management of a symptomatic regrowing lesion. None of the patients showed pathological evidence of tumor recurrence. Clinical and magnetic resonance imaging data for each of the 10 patients were then studied retrospectively. Results: We provide evidence to show that radiosurgery-induced leukoencephalopathy may present as an advancing process that extends beyond the original high-dose radiation field. Neuropathologic examination of the resected tissue revealed traditionally known leukoencephalopathic changes including demyelination, coagulation necrosis, and vascular sclerosis. Unexpectedly, small and medium-sized vessels revealed transmural T-cell infiltration indicative of active vasculitis. Conclusions: We propose that the presence of a vasculitic component in association with radiation-induced leukoencephalopathy may facilitate the progressive nature of the condition. It may also explain the resemblance of delayed leukoencephalopathy with recurring tumor on virtually all imaging modalities used for posttreatment follow-up.

  17. Study of efficacy and toxicity of hypofractionated thoracic radiotherapy 17 gray in 2 fractions for palliation in advanced non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Arif, S.; Rasul, S.; Haider, N.; Mahmood, A.; Syed, A.S.; Nadeem, M.

    2012-01-01

    Objective: To determine the efficacy and toxicity of hypofractionated thoracic radiotherapy 17 Gray (Gy) in 2 fractions for palliation in advanced non-small-cell lung carcinoma. Study design: A quasi-experimental study. Place and duration of study: Oncology department, Combined Military Hospital, Rawalpindi, from 4th July 2008 to 4th Nov 2009. Material and Methods: Fifty four patients with histologically and/or cytologically confirmed unresectable stages III and IV non small cell lung cancer, with performance status 2 or 3 and expected survival > 2 months were treated with megavoltage radiation therapy 17 Gy in 2 fractions one week apart, with symptoms due to intrathoracic disease (cough, dyspnea and hemoptysis) and toxicity due to radiation therapy (dysphagia secondary to esophagitis) assessed as per common toxicity criteria adverse event version 3.0 on day 0 before treatment and day 30 after start of treatment. Results: Grades of cough, hemoptysis and dyspnea showed significant improvement after treatment (p<0.001). A total of 42.68% patients showed an improvement in grade of cough (23 out of 54 patients), 85.7% of patients showed improvement in grade of hemoptysis (36 out of 42 patients) and 55.65% patients showed improvement in grade of dyspnea (30 out of 54 patients). Twenty two point two percent patients (12 out of 54) showed increase in grade of dysphagia. Although, there was a statistically significant increase in grade of dysphagia after treatment but it was limited to grade 1 and 2 only. Considering that no patient had grade 3 or 4 dysphagia, this toxicity was acceptable. Conclusion: Based on our results hypofractionated thoracic radiotherapy, 17 Gy in 2 fractions, is effective with acceptable toxicity in palliation in advanced non small cell lung cancer and is recommended as it will result in shorter duration of hospital stay and low hospital stay charges. (author)

  18. Image Guided Hypofractionated Radiotherapy by Helical Tomotherapy for Prostate Carcinoma: Toxicity and Impact on Nadir PSA

    Directory of Open Access Journals (Sweden)

    Salvina Barra

    2014-01-01

    Full Text Available Aim. To evaluate the toxicity of a hypofractionated schedule for primary radiotherapy (RT of prostate cancer as well as the value of the nadir PSA (nPSA and time to nadir PSA (tnPSA as surrogate efficacy of treatment. Material and Methods. Eighty patients underwent hypofractionated schedule by Helical Tomotherapy (HT. A dose of 70.2 Gy was administered in 27 daily fractions of 2.6 Gy. Acute and late toxicities were graded on the RTOG/EORTC scales. The nPSA and the tnPSA for patients treated with exclusive RT were compared to an equal cohort of 20 patients treated with conventional fractionation and standard conformal radiotherapy. Results. Most of patients (83% did not develop acute gastrointestinal (GI toxicity and 50% did not present genitourinary (GU toxicity. After a median follow-up of 36 months only grade 1 of GU and GI was reported in 6 and 3 patients as late toxicity. Average tnPSA was 30 months. The median value of nPSA after exclusive RT with HT was 0.28 ng/mL and was significantly lower than the median nPSA (0.67 ng/mL of the conventionally treated cohort (P=0.02. Conclusions. Hypofractionated RT schedule with HT for prostate cancer treatment reports very low toxicity and reaches a low level of nPSA that might correlate with good outcomes.

  19. 4D radiobiological modelling of the interplay effect in conventionally and hypofractionated lung tumour IMRT.

    Science.gov (United States)

    Selvaraj, J; Uzan, J; Baker, C; Nahum, A

    2015-01-01

    To study the impact of the interplay between respiration-induced tumour motion and multileaf collimator leaf movements in intensity-modulated radiotherapy (IMRT) as a function of number of fractions, dose rate on population mean tumour control probability ([Formula: see text]) using an in-house developed dose model. Delivered dose was accumulated in a voxel-by-voxel basis inclusive of tumour motion over the course of treatment. The effect of interplay on dose and [Formula: see text] was studied for conventionally and hypofractionated treatments using digital imaging and communications in medicine data sets. Moreover, the effect of dose rate on interplay was also studied for single-fraction treatments. Simulations were repeated several times to obtain [Formula: see text] for each plan. The average variation observed in mean dose to the target volumes were -0.76% ± 0.36% for the 20-fraction treatment and -0.26% ± 0.68% and -1.05% ± 0.98% for the three- and single-fraction treatments, respectively. For the 20-fraction treatment, the drop in [Formula: see text] was -1.05% ± 0.39%, whereas for the three- and single-fraction treatments, it was -2.80% ± 1.68% and -4.00% ± 2.84%, respectively. By reducing the dose rate from 600 to 300 MU min(-1) for the single-fraction treatments, the drop in [Formula: see text] was reduced by approximately 1.5%. The effect of interplay on [Formula: see text] is negligible for conventionally fractionated treatments, whereas considerable drop in [Formula: see text] is observed for the three- and single-fraction treatments. Reduced dose rate could be used in hypofractionated treatments to reduce the interplay effect. A novel in silico dose model is presented to determine the impact of interplay effect in IMRT treatments on [Formula: see text].

  20. Computer modelling of radiation-induced bystander effect

    International Nuclear Information System (INIS)

    Khvostunov, Igor K.; Nikjoo, Hooshang

    2002-01-01

    Radiation-induced genomic instability and bystander effects are now well established consequences of exposure of living cells to ionising radiation. It has been observed that cells not directly hit by radiation tracks may still exhibit radiation effects. We present a quantitative modelling of the radiation-induced bystander effect based on a diffusion model of spreading the bystander signal. The model assumes the bystander factor to be a protein of low molecular weight, given out by the hit cell, diffusing in the medium and reacting with non-hit cells. The model calculations successfully predict the results of cell survival in an irradiated conditioned medium. The model predicts the shape of dose-effect relationship for cell survival and oncogenic transformation induced by broad-beam and micro-beam irradiation by alpha-particles. (author)

  1. Extracranial Facial Nerve Schwannoma Treated by Hypo-fractionated CyberKnife Radiosurgery

    OpenAIRE

    Sasaki, Ayaka; Miyazaki, Shinichiro; Hori, Tomokatsu

    2016-01-01

    Facial nerve schwannoma is a rare intracranial tumor. Treatment for this benign tumor has been controversial. Here, we report a case of extracranial facial nerve schwannoma treated successfully by hypo-fractionated CyberKnife (Accuray, Sunnyvale, CA) radiosurgery?and discuss the efficacy of this treatment. A 34-year-old female noticed a swelling in her right mastoid process. The lesion enlarged over a seven-month period, and she experienced facial spasm on the right side. She was diagnosed wi...

  2. Comparing the effects of conventional and hypofractionated radiotherapies on early skin toxicity and cosmetic outcomes after breast cancer conserving surgery

    Directory of Open Access Journals (Sweden)

    Amouzegar Hashemi F

    2012-12-01

    Full Text Available Background: The high number of breast cancer patients who receive radiation therapy after surgery has caused many to think about a shorter period of radiotherapy, which can significantly reduce the radiotherapy machine time, labor hours, and fewer patient visits. This study was designed to evaluate the acute skin effects and cosmetic outcomes of short course radiotherapy in early-stage breast cancer in comparison with the conventional treatment method.Methods: Fifty-two patients with operable breast cancer (pT1-3pN0M0 who underwent breast conservation surgery in Tehran Cancer Institute during January 2011 to January 2012, were randomly assigned to undergo radiotherapy by either receiving conventional treatment (dose: 50 Gy in 25 fractions with subsequent electron boost or a short-course hypofractionated radiotherapy (dose: 42.5 Gy in 16 fractions and a subsequent electron boost.Results: There were no skin changes during the first or the second week of treatment in the two groups. Cutaneous complications began after the third week as grade 1 skin toxicity after termination of the short-course radiotherapy but there were no difference in complication rate after four weeks of treatment. Six months and one year after treatment, there were no differences in terms of skin complications or cosmetic outcomes between the two groups.Conclusion: Although the use of a whole-breast irradiation with a hypofractionated schedule was associated with desirable outcomes, in term of skin toxicity and cosmetics, but longer follow-up periods with larger sample sizes are needed to confirm these results.

  3. Radiation-induced chromosomal instability

    International Nuclear Information System (INIS)

    Ritter, S.

    1999-01-01

    Recent studies on radiation-induced chromosomal instability in the progeny of exposed mammalian cells were briefly described as well as other related studies. For the analysis of chromosomal damage in clones, cells were seeded directly after exposure in cell well-dish to form single cell clones and post-irradiation chromosome aberrations were scored. Both exposure to isoeffective doses of X-ray or 270 MeV/u C-ions (13 keV/μm) increased the number of clones with abnormal karyotype and the increase was similar for X-ray and for C-ions. Meanwhile, in the progeny of cells for mass cultures, there was no indication of a delayed expression of chromosomal damage up to 40 population doublings after the exposure. A high number of aberrant cells were only observed directly after exposure to 10.7 MeV/u O-ions, i.e. in the first cycle cells and decreased with subsequent cell divisions. The reason for these differences in the radiation-induced chromosomal instability between clonal isolates and mass culture has not been clarified. Recent studies indicated that genomic instability occurs at a high frequency in the progeny of cells irradiated with both sparsely and densely ionizing radiation. Such genomic instability is thought likely to increase the risk of carcinogenesis, but more data are required for a well understanding of the health risks resulting from radiation-induced delayed instability. (M.N.)

  4. Hypo-fractionated treatment in radiotherapy: radio-biological models Tcp and NTCP; Tratamiento hipofraccionado en radioterapia: modelos radiobiologicos TCP y NTCP

    Energy Technology Data Exchange (ETDEWEB)

    Astudillo V, A. J.; Mitsoura, E. [Universidad Autonoma del Estado de Mexico, Facultad de Medicina, Paseo Tollocan s/n, 50180 Toluca, Estado de Mexico (Mexico); Paredes G, L. [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico); Resendiz G, G., E-mail: lydia.paredes@inin.gob.mx [Hospital Medica Sur, Departamento de Radioterapia, Puente de Piedra 150, Col. Toriello Guerra, 14050 Mexico D. F. (Mexico)

    2014-08-15

    At the present time the breast cancer in Mexico has the first place of incidence of the malignant neoplasia s in the women, and represents 11.34% of all the cancer cases. On the other hand, the treatments for cancer by means of ionizing radiations have been dominated under the approaches of the medical radio-oncologists which have been based on test and error by many years. The radio-biological models, as the Tcp, NTCP and dosimetric variables, for their clinical application in the conventional radiotherapy with hypo-fractionation have as purpose predicting personalized treatment plans that they present most probability of tumor control and minor probability of late reactions, becoming this way support tools in the decisions taking for the patient treatments planning of Medical Physicists and Radio-oncologists. (Author)

  5. Lack of benefit from a short course of androgen deprivation for unfavorable prostate cancer patients treated with an accelerated hypofractionated regime

    International Nuclear Information System (INIS)

    Martinez, Alvaro A.; Demanes, D. Jeffrey; Galalae, Razvan; Vargas, Carlos; Bertermann, Hagen; Rodriguez, Rodney; Gustafson, Gary; Altieri, Gillian; Gonzalez, Jose

    2005-01-01

    Purpose: High-dose radiotherapy, delivered in an accelerated hypofractionated course, was utilized to treat prostate cancer. Therapy consisted of external beam radiotherapy (EBRT) and transrectal ultrasound (TRUS)-guided conformally modulated high-dose rate (HDR) brachytherapy. The purpose of this report is (1) to assess long-term comparative outcomes from three trials using similar accelerated hypofractionated regimes; and (2) to examine the long-term survival impact of a short course of ≤6 months adjuvant/concurrent androgen deprivation when a very high radiation dose was delivered. Methods and Materials: Between 1986 and 2000, 1,260 patients were treated at three institutions with pelvic EBRT (36-50 Gy) integrated with HDR prostate brachytherapy. The total dose including brachytherapy was given over 5 weeks. The biologic equivalent EBRT dose ranged between 90 and 123 Gy (median, 102 Gy) using an α /β of 1.2. Patient eligibility criteria included a pretreatment prostate-specific antigen ≥10, Gleason score ≥7, or clinical stage ≥T2b. A total of 1,260 patients were treated, and 934 meet the criteria. Kiel University Hospital treated 198 patients; William Beaumont Hospital, 315; and California Endocurietherapy Cancer Center, 459 patients. Brachytherapy dose regimes were somewhat different between centers and the dose was escalated from 5.5 x 3 to 15 Gy x 2 Gy. Patients were divided for analysis between the 406 who received up to 6 months of androgen deprivation therapy and the 528 patients who did not. All patients had a minimum follow-up of 18 months (3 times the exposure to androgen deprivation therapy). The American Society for Therapeutic Radiology and Oncology biochemical failure definition was used. Results: Mean age was 69 years. Median follow-up time was 4.4 years (range, 1.5-14.5); 4 years for androgen deprivation therapy patients and 4.9 for radiation alone. There was no difference at 5 and 8 years in overall survival, cause-specific survival, or

  6. Role of neurotensin in radiation-induced hypothermia in rats

    International Nuclear Information System (INIS)

    Kandasamy, S.B.; Hunt, W.A.; Harris, A.H.

    1991-01-01

    The role of neurotensin in radiation-induced hypothermia was examined. Intracerebroventricular (ICV) administration of neurotensin produced dose-dependent hypothermia. Histamine appears to mediate neurotensin-induced hypothermia because the mast cell stabilizer disodium cromoglycate and antihistamines blocked the hypothermic effects of neurotensin. An ICV pretreatment with neurotensin antibody attenuated neurotensin-induced hypothermia, but did not attenuate radiation-induced hypothermia, suggesting that radiation-induced hypothermia was not mediated by neurotensin

  7. Relationship between radiation induced activation of DNA repair genes and radiation induced apoptosis in human cell line A431

    International Nuclear Information System (INIS)

    Bom, Hee Seung; Min, Jung Jun; Kim, Kyung Keun; Choi, Keun Hee

    2000-01-01

    The purpose of this study was to evaluate the relationship between radiation-induced acivation of DNA repair genes and radiation induced apoptosis in A431 cell line. Five and 25 Gys of gamma radiation were given to A431 cells by a Cs-137 cell irradiator. Apoptosis was evaluated by flow cytometry using annexin V-fluorescein isothiocyanate and propidium iodide staining. The expression of DNA repair genes was evaluated by both Northern and Western blot analyses. The number of apoptotic cells increased with the increased radiation dose. It increased most significantly at 12 hours after irradiation. Expression of p53, p21, and ℎRAD50 reached the highest level at 12 hours after 5 Gy irradiation. In response to 25 Gy irradiation, ℎRAD50 and p21 were expressed maximally at 12 hours, but p53 and GADD45 genes showed the highest expression level after 12 hours. Induction of apoptosis and DNA repair by ionizing radiation were closely correlated. The peak time of inducing apoptosis and DNA repair was 12 hours in this study model. ℎRAD50, a recently discovered DNA repair gene, was also associated with radiation-induced apoptosis.=20

  8. Study on radiation-inducible genes

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sang Yong; Kim, Dong Ho; Joe, Min Ho; Song, Hyu Npa

    2012-01-15

    Transcription of previously identified radiation-inducible genes, uscA and cyoA, was examined responding to radiation. The putative promoter regions of both genes were cloned into pRS415 vector containing lacZ, and the core promoter region necessary for radiation response were determined through promoter deletion method. To investigate the role of uscA, which is assumed to be small RNA related with radiation response, a deletion mutant strain of uscA was constructed. However, uscA deletion did not affect bacterial survival against radiation exposure. The use of bacteria as anticancer agents has attracted interest. In this study, we tried to develop tumor targeting bacteria in which the radiation-inducible promoter activate a transgene encoding a cytotoxic protein. For outward secretion of anticancer protein produced inside bacteria, the N-terminal 140 amino acid of SspH1 was found to function as a secretion signal peptide. To create an attenuated tumor-targeting bacteria, Salmonella ptsI mutant strain was constructed, and we found that its virulence decreased. Finally, the tumor-targeting ability of ptsI mutant was verified by the use of in-vivo imaging analysis.

  9. Study on radiation-inducible genes

    International Nuclear Information System (INIS)

    Lim, Sang Yong; Kim, Dong Ho; Joe, Min Ho; Song, Hyu Npa

    2012-01-01

    Transcription of previously identified radiation-inducible genes, uscA and cyoA, was examined responding to radiation. The putative promoter regions of both genes were cloned into pRS415 vector containing lacZ, and the core promoter region necessary for radiation response were determined through promoter deletion method. To investigate the role of uscA, which is assumed to be small RNA related with radiation response, a deletion mutant strain of uscA was constructed. However, uscA deletion did not affect bacterial survival against radiation exposure. The use of bacteria as anticancer agents has attracted interest. In this study, we tried to develop tumor targeting bacteria in which the radiation-inducible promoter activate a transgene encoding a cytotoxic protein. For outward secretion of anticancer protein produced inside bacteria, the N-terminal 140 amino acid of SspH1 was found to function as a secretion signal peptide. To create an attenuated tumor-targeting bacteria, Salmonella ptsI mutant strain was constructed, and we found that its virulence decreased. Finally, the tumor-targeting ability of ptsI mutant was verified by the use of in-vivo imaging analysis

  10. TH-A-BRD-01: Radiation Biology for Radiation Therapy Physicists

    International Nuclear Information System (INIS)

    Orton, C; Borras, C; Carlson, D

    2014-01-01

    Mechanisms by which radiation kills cells and ways cell damage can be repaired will be reviewed. The radiobiological parameters of dose, fractionation, delivery time, dose rate, and LET will be discussed. The linear-quadratic model for cell survival for high and low dose rate treatments and the effect of repopulation will be presented and discussed. The rationale for various radiotherapy techniques such as conventional fractionation, hyperfractionation, hypofractionation, and low and high dose rate brachytherapy, including permanent implants, will be presented. The radiobiological principles underlying radiation protection guidelines and the different radiation dosimetry terms used in radiation biology and in radiation protection will be reviewed. Human data on radiation induced cancer, including increases in the risk of second cancers following radiation therapy, as well as data on radiation induced tissue reactions, such as cardiovascular effects, for follow up times up to 20–40 years, published by ICRP, NCRP and BEIR Committees, will be examined. The latest risk estimates per unit dose will be presented. Their adoption in recent radiation protection standards and guidelines and their impact on patient and workers safety in radiotherapy will be discussed. Biologically-guided radiotherapy (BGRT) provides a systematic method to derive prescription doses that integrate patient-specific information about tumor and normal tissue biology. Treatment individualization based on patient-specific biology requires the identification of biological objective functions to facilitate the design and comparison of competing treatment modalities. Biological objectives provide a more direct approach to plan optimization instead of relying solely on dose-based surrogates and can incorporate factors that alter radiation response, such as DNA repair, tumor hypoxia, and relative biological effectiveness. We review concepts motivating biological objectives and provide examples of how

  11. TH-A-BRD-01: Radiation Biology for Radiation Therapy Physicists

    Energy Technology Data Exchange (ETDEWEB)

    Orton, C [Wayne State University, Grosse Pointe, MI (United States); Borras, C [Radiological Physics and Health Services, Washington, DC (United States); Carlson, D [Yale University School of Medicine, New Haven, CT (United States)

    2014-06-15

    Mechanisms by which radiation kills cells and ways cell damage can be repaired will be reviewed. The radiobiological parameters of dose, fractionation, delivery time, dose rate, and LET will be discussed. The linear-quadratic model for cell survival for high and low dose rate treatments and the effect of repopulation will be presented and discussed. The rationale for various radiotherapy techniques such as conventional fractionation, hyperfractionation, hypofractionation, and low and high dose rate brachytherapy, including permanent implants, will be presented. The radiobiological principles underlying radiation protection guidelines and the different radiation dosimetry terms used in radiation biology and in radiation protection will be reviewed. Human data on radiation induced cancer, including increases in the risk of second cancers following radiation therapy, as well as data on radiation induced tissue reactions, such as cardiovascular effects, for follow up times up to 20–40 years, published by ICRP, NCRP and BEIR Committees, will be examined. The latest risk estimates per unit dose will be presented. Their adoption in recent radiation protection standards and guidelines and their impact on patient and workers safety in radiotherapy will be discussed. Biologically-guided radiotherapy (BGRT) provides a systematic method to derive prescription doses that integrate patient-specific information about tumor and normal tissue biology. Treatment individualization based on patient-specific biology requires the identification of biological objective functions to facilitate the design and comparison of competing treatment modalities. Biological objectives provide a more direct approach to plan optimization instead of relying solely on dose-based surrogates and can incorporate factors that alter radiation response, such as DNA repair, tumor hypoxia, and relative biological effectiveness. We review concepts motivating biological objectives and provide examples of how

  12. Role of endothelium in radiation-induced normal tissue damages

    International Nuclear Information System (INIS)

    Milliat, F.

    2007-05-01

    More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

  13. SU-F-T-432: Magnetic Field Dose Effects for Various Radiation Beam Geometries for Patients Treated with Hypofractionated Partial Breast Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lim-Reinders, S [Sunnybrook Odette Cancer Centre, Toronto (Canada); University of Toronto, Department of Physics (Canada); Keller, B; McCann, C; Sahgal, A; Lee, J; Kim, A [Sunnybrook Odette Cancer Centre, Toronto (Canada); University of Toronto, Department of Radiation Oncology (Canada)

    2016-06-15

    Purpose: Hypofractionated partial breast irradiation (HPBI) is being used at our clinic to treat inoperable breast cancer patients who have advanced disease. We are investigating how these patients could benefit from being treated in an MRI-linac, where real-time daily MRI tumor imaging and plan adaptation would be possible. As a first step, this study evaluates the dosimetric impact of the magnetic field for different radiation beam geometries on relevant OARs. Methods: Five patients previously treated using HPBI were selected. Six treatment plans were generated for each patient, evaluating three beam geometries (VMAT, IMRT, 3DCRT) with and without B{sub 0}=1.5 T. The Monaco TPS was used with the Elekta MRI-Linac beam model, where the magnetic field is orthogonal to the radiation beam. All plans were re-scaled to the same isocoverage with a prescription of 40Gy/5 to the PTV. Plans were evaluated for the effect of the magnetic field and beam modality on skin V{sub 3} {sub 0}, lung V{sub 2} {sub 0} and mean heart dose. Results: Averaged over all patients, skin V{sub 3} {sub 0}for 3DCRT was higher than VMAT and IMRT (by +22% and +21%, with B{sub 0}-ON). The magnetic field caused larger increases in skin V{sub 3} {sub 0}for 3DCRT (+8%) than VMAT (+3%) and IMRT (+4%) compared with B{sub 0}-OFF. With B{sub 0}-ON, 3DCRT had a markedly lower mean heart dose than VMAT (by 538cGy) and IMRT (by 562cGy); for lung V{sub 2} {sub 0}, 3DCRT had a marginally lower dose than VMAT (by −2.2%) and IMRT (also −2.2%). The magnetic field had minimal effect on the mean heart dose and lung V{sub 2} {sub 0} for all geometries. Conclusion: The decreased skin dose in VMAT and IMRT can potentially mitigate the effects of skin reactions for HPBI in an MRI-linac. This study illustrated that more beam angles may result in lower skin toxicity and better tumor conformality, with the trade-off of elevated heart and lung doses. We are receiving funding support from Elekta.

  14. Radiogenic Side Effects After Hypofractionated Stereotactic Photon Radiotherapy of Choroidal Melanoma in 212 Patients Treated Between 1997 and 2007

    Energy Technology Data Exchange (ETDEWEB)

    Dunavoelgyi, Roman [Department of Ophthalmology, Medical University of Vienna, Vienna (Austria); Dieckmann, Karin [Department of Radiology, Medical University of Vienna, Vienna (Austria); Gleiss, Andreas [Section of Clinical Biometrics, Medical University of Vienna, Vienna (Austria); Sacu, Stefan; Kircher, Karl; Georgopoulos, Michael [Department of Ophthalmology, Medical University of Vienna, Vienna (Austria); Georg, Dietmar [Department of Radiology, Medical University of Vienna, Vienna (Austria); Zehetmayer, Martin [Department of Ophthalmology, Medical University of Vienna, Vienna (Austria); Poetter, Richard [Department of Radiology, Medical University of Vienna, Vienna (Austria)

    2012-05-01

    Purpose: To evaluate side effects of hypofractionated stereotactic photon radiotherapy for patients with choroidal melanoma. Patients and Methods: Two hundred and twelve patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at the Medical University of Vienna between 1997 and 2007 with a Linac with 6-MV photon beams in five fractions with 10, 12, or 14 Gy per fraction. Examinations for radiogenic side effects were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and then once a year thereafter until 10 years after radiotherapy. Adverse side effects were assessed using slit-lamp examination, funduscopy, gonioscopy, tonometry, and, if necessary, fundus photography and fluorescein angiography. Evaluations of incidence of side effects are based on an actuarial analysis. Results: One hundred and eighty-nine (89.2%) and 168 (79.2%) of the tumors were within 3 mm of the macula and the optic disc, respectively. The five most common radiotherapy side effects were retinopathy and optic neuropathy (114 cases and 107 cases, respectively), cataract development (87 cases), neovascular glaucoma (46 cases), and corneal epithelium defects (41 cases). In total, 33.6%, 38.5%, 51.2%, 75.5%, and 77.6% of the patients were free of any radiation retinopathy, optic neuropathy, cataract, neovascular glaucoma, or corneal epithelium defects 5 years after radiotherapy, respectively. Conclusion: In centrally located choroidal melanoma hypofractionated stereotactic photon radiotherapy shows a low to moderate rate of adverse long-term side effects comparable with those after proton beam radiotherapy. Future fractionation schemes should seek to further reduce adverse side effects rate while maintaining excellent local tumor control.

  15. Radiogenic Side Effects After Hypofractionated Stereotactic Photon Radiotherapy of Choroidal Melanoma in 212 Patients Treated Between 1997 and 2007

    International Nuclear Information System (INIS)

    Dunavoelgyi, Roman; Dieckmann, Karin; Gleiss, Andreas; Sacu, Stefan; Kircher, Karl; Georgopoulos, Michael; Georg, Dietmar; Zehetmayer, Martin; Poetter, Richard

    2012-01-01

    Purpose: To evaluate side effects of hypofractionated stereotactic photon radiotherapy for patients with choroidal melanoma. Patients and Methods: Two hundred and twelve patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at the Medical University of Vienna between 1997 and 2007 with a Linac with 6-MV photon beams in five fractions with 10, 12, or 14 Gy per fraction. Examinations for radiogenic side effects were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and then once a year thereafter until 10 years after radiotherapy. Adverse side effects were assessed using slit-lamp examination, funduscopy, gonioscopy, tonometry, and, if necessary, fundus photography and fluorescein angiography. Evaluations of incidence of side effects are based on an actuarial analysis. Results: One hundred and eighty-nine (89.2%) and 168 (79.2%) of the tumors were within 3 mm of the macula and the optic disc, respectively. The five most common radiotherapy side effects were retinopathy and optic neuropathy (114 cases and 107 cases, respectively), cataract development (87 cases), neovascular glaucoma (46 cases), and corneal epithelium defects (41 cases). In total, 33.6%, 38.5%, 51.2%, 75.5%, and 77.6% of the patients were free of any radiation retinopathy, optic neuropathy, cataract, neovascular glaucoma, or corneal epithelium defects 5 years after radiotherapy, respectively. Conclusion: In centrally located choroidal melanoma hypofractionated stereotactic photon radiotherapy shows a low to moderate rate of adverse long-term side effects comparable with those after proton beam radiotherapy. Future fractionation schemes should seek to further reduce adverse side effects rate while maintaining excellent local tumor control.

  16. Heavy-ion radiation induced bystander effect in mice

    Science.gov (United States)

    Liang, Shujian; Sun, Yeqing; Zhang, Meng; Wang, Wei; Cui, Changna

    2012-07-01

    Radiation-induced bystander effect is defined as the induction of damage in neighboring non-hit cells by signals released from directly-irradiated cells. Recently, Low dose of high LET radiation induced bystander effects in vivo have been reported more and more. It has been indicated that radiation induced bystander effect was localized not only in bystander tissues but also in distant organs. Genomic, epigenetic, metabolomics and proteomics play significant roles in regulating heavy-ion radiation stress responses in mice. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male mice head were exposed to 2000mGy dose of 12C heavy-ion radiation and the distant organ liver was detected on 1h, 6h, 12h and 24h after radiation, respectively. MSAP was used to monitor the level of polymorphic DNA methylation changes. The results show that heavy-ion irradiate mouse head can induce liver DNA methylation changes significantly. The percent of DNA methylation changes are time-dependent and highest at 6h after radiation. We also prove that the hypo-methylation changes on 1h and 6h after irradiation. But the expression level of DNA methyltransferase DNMT3a is not changed. UPLC/Synapt HDMS G2 was employed to detect the proteomics of bystander liver 1h after irradiation. 64 proteins are found significantly different between treatment and control group. GO process show that six of 64 which were unique in irradiation group are associated with apoptosis and DNA damage response. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in distant organ liver. Moreover, our findings are important to understand the molecular mechanism of radiation induced bystander effects in vivo.

  17. A study of radiation-induced cerebral vascular injury in nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis.

    Directory of Open Access Journals (Sweden)

    Jianhong Ye

    Full Text Available To investigate radiation-induced carotid and cerebral vascular injury and its relationship with radiation-induced temporal lobe necrosis in nasopharyngeal carcinoma (NPC patients.Fifty eight NPC patients with radiation-induced temporal lobe necrosis (TLN were recruited in the study. Duplex ultrasonography was used to scan bilateral carotid arterials to evaluate the intima-media thickness (IMT and occurrence of plaque formation. Flow velocities of bilateral middle cerebral arteries (MCAs, internal carotid arteries (ICAs and basal artery (BA were estimated through Transcranial Color Doppler (TCD. The results were compared with data from 33 patients who were free from radiation-induced temporal lobe necrosis after radiotherapy and 29 healthy individuals.Significant differences in IMT, occurrence of plaques of ICAs and flow velocities of both MCAs and ICAs were found between patients after radiotherapy and healthy individuals (p<0.05. IMT had positive correlation with post radiation interval (p = 0.049. Compared with results from patients without radiation-induced TLN, the mean IMT was significantly thicker in patients with TLN (p<0.001. Plaques were more common in patients with TLN than patients without TLN (p = 0.038. In addition, flow velocities of MCAs and ICAs in patients with TLN were much faster (p<0.001, p<0.001. Among patients with unilateral TLN, flow velocity of MCAs was significantly different between ipsilateral and contralateral sides to the lesion (p = 0.001.Thickening of IMT, occurrence of plaque formation and hemodynamic abnormality are more common in patients after radiotherapy, especially in those with TLN, compared with healthy individuals.

  18. Radiation-induced heart injury. Radiopathological study

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Y; Niibe, H [Gunma Univ., Maebashi (Japan). School of Medicine

    1975-11-01

    In order to identify radiation-induced heart injury and to differentiate it from heart disease, an attempt was made to clarify post-irradiation heart injury by investigating the histological changes which occur during the interval between the irradiation and the time of demonstrable histological changes. A study was made of 83 autopsies in which most of the primary neoplasms were breast cancers, lung cancers and mediastinal tumors. In 43 of these autopsies the heart had been irradiated. Sixty eight dd-strain mice were also used for microautoradiographic study. Histological changes in the heart were observed in 27 of the 43 cases receiving irradiation. The limit of the tolerance dose to the heart for indicating histological changes was 1220 ret in humans. The latent period without histological changes was 2.7 months after initiation of radiation therapy. Greater heart injury was observed after re-irradiation or after the combined therapy of radiation and chemotherapy especially mitomycin (MMC). The histological findings after treatment with MMC were similar to those of radiation-induced heart injury. Results of the study indicate that the damage is secondary to radiation-induced changes of the vascula connective tissue.

  19. Quad shot - hypofractionated radiotherapy for palliation in advanced squamous cell carcinoma of head and neck

    International Nuclear Information System (INIS)

    Maqsood, T.; Ali, U.; Arif, S.

    2017-01-01

    The objective of this study was to determine the efficacy of quad-shot radiation therapy for palliation in locally advanced and metastatic inoperable squamous cell carcinomas of head and neck. Study Design: A quasi-experimental study. Place and Duration of Study: Oncology department, Combined Military Hospital Rawalpindi, from Sep 2012 to Sep 2013. Material and Methods: Thirty five patients were included with histologically confirmed advanced inoperable squamous cell carcinoma in head and neck region, performance status 2 or 3 and survival =3 months. Patients were treated with radiation therapy 14 Gy in four fractions, megavoltage beam, twice daily fractions (at least 6 hours apart), for 2 consecutive days. Symptoms due to cancer (pain and dysphagia) were assessed as per common toxicity criteria adverse event version 4.0 on day 0 before treatment and day 21 after start of treatment. Results: Grades of pain and dysphagia showed significant improvement after treatment with a p-value <0.001. A total of 91.4% patients showed an improvement in grade of pain (32 out of 35 patients) and 45.7% of patients showed improvement in grade of dysphagia (16 out of 35 patients). There was a statistically significant decrease in grades of pain and dysphagia after treatment. Conclusion: The short duration of hypofractionated radiotherapy with Quad Shot was effective with respect to symptom palliation in locally advanced and metastatic inoperable head and neck cancers.

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

    Directory of Open Access Journals (Sweden)

    Lominska Chris E

    2012-05-01

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

  1. Radiation-induced degradation of pollutants

    International Nuclear Information System (INIS)

    Proksch, E.

    1988-01-01

    This article outlines the fundamentals of radiation-induced degradation of noxious substances in drinking water and waste water and discusses the relevant literature. Radiation methods present a number of advantages and disadvantages, which should carefully be considered in each case. In many cases, there seems to be merit in combining the radiation method with other techniques, as e.g. ozone treatement and biodegradation. 30 refs., 3 figs. (Author)

  2. Pyruvate metabolism: A therapeutic opportunity in radiation-induced skin injury

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Hyun; Kang, Jeong Wook [Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Lee, Dong Won [Department of Plastic Surgery, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Oh, Sang Ho [Department of Dermatology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Lee, Yun-Sil [College of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewah Womans University, Seoul 120-750 (Korea, Republic of); Lee, Eun-Jung [Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Cho, Jaeho, E-mail: jjhmd@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    2015-05-08

    Ionizing radiation is used to treat a range of cancers. Despite recent technological progress, radiation therapy can damage the skin at the administration site. The specific molecular mechanisms involved in this effect have not been fully characterized. In this study, the effects of pyruvate, on radiation-induced skin injury were investigated, including the role of the pyruvate dehydrogenase kinase 2 (PDK2) signaling pathway. Next generation sequencing (NGS) identified a wide range of gene expression differences between the control and irradiated mice, including reduced expression of PDK2. This was confirmed using Q-PCR. Cell culture studies demonstrated that PDK2 overexpression and a high cellular pyruvate concentration inhibited radiation-induced cytokine expression. Immunohistochemical studies demonstrated radiation-induced skin thickening and gene expression changes. Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness and inflammatory cytokine expression. These findings indicated that regulation of the pyruvate metabolic pathway could provide an effective approach to the control of radiation-induced skin damage. - Highlights: • The effects of radiation on skin thickness in mice. • Next generation sequencing revealed that radiation inhibited pyruvate dehydrogenase kinase 2 expression. • PDK2 inhibited irradiation-induced cytokine gene expression. • Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness.

  3. Accelerated hypofractionated radiotherapy as adjuvant regimen after conserving surgery for early breast cancer: interim report of toxicity after a minimum follow up of 3 years

    Science.gov (United States)

    2010-01-01

    Background Accelerated hypofractionation is an attractive approach for adjuvant whole breast radiotherapy. In this study we evaluated the adverse effects at least 3 years post an accelerated hypofractionated whole breast radiotherapy schedule. Methods From October 2004 to March 2006, 39 consecutive patients aged over 18 years with pTis, pT1-2, pN0-1 breast adenocarcinoma who underwent conservative surgery were treated with an adjuvant accelerated hypofractionated radiotherapy schedule consisting of 34 Gy in 10 daily fractions over 2 weeks to the whole breast, followed after 1 week by an electron boost dose of 8 Gy in a single fraction to the tumour bed. Skin and lung radiation toxicity was evaluated daily during therapy, once a week for one month after radiotherapy completion, every 3 months for the first year and from then on every six months. In particular lung toxicity was investigated in terms of CT density evaluation, pulmonary functional tests, and clinical and radiological scoring. Paired t-test, Chi-square test and non-parametric Wilcoxon test were performed. Results After a median follow-up of 43 months (range 36-52 months), all the patients are alive and disease-free. None of the patients showed any clinical signs of lung toxicity, no CT-lung toxicity was denoted by radiologist on CT lung images acquired about 1 year post-radiotherapy, no variation of pulmonary density evaluated in terms of normalised Hounsfield numbers was evident. Barely palpable increased density of the treated breast was noted in 9 out of 39 patients (in 2 patients this toxicity was limited to the boost area) and teleangectasia (radiotherapy schedule investigated in this study (i.e 34 Gy in 3.4 Gy/fr plus boost dose of 8 Gy in single fraction) is a feasible and safe treatment and does not lead to adjunctive acute and late toxicities. A longer follow up is necessary to confirm these favourable results. PMID:20100335

  4. Hypofractionated stereotactic boost in intermediate risk prostate carcinoma: Preliminary results of a multicenter phase II trial (CKNO-PRO.

    Directory of Open Access Journals (Sweden)

    David Pasquier

    Full Text Available Dose escalation may improve curability in intermediate-risk prostate carcinoma. A multicenter national program was developed to assess toxicity and tumor response with hypofractionated stereotactic boost after conventional radiotherapy in intermediate-risk prostate cancer.Between August 2010 and April 2013, 76 patients with intermediated-risk prostate carcinoma were included in the study. A first course delivered 46 Gy by IMRT (68.4% of patients or 3D conformal radiotherapy (31.6% of patients. The second course delivered a boost of 18 Gy (3x6Gy within 10 days. Gastrointestinal (GI and genitourinary (GU toxicities were evaluated as defined by NCI-CTCAE (v4.0. Secondary outcome measures were local control, overall and metastasis-free survival, PSA kinetics, and patient functional status (urinary and sexual according to the IIEF5 and IPSS questionnaires.The overall treatment time was 45 days (median, range 40-55. Median follow-up was 26.4 months (range, 13.6-29.9 months. Seventy-seven per cent (n = 58 of patients presented a Gleason score of 7. At 24 months, biological-free survival was 98.7% (95% CI, 92.8-99.9% and median PSA 0.46 ng/mL (range, 0.06-6.20 ng/mL. Grade ≥2 acute GI and GU toxicities were 13.2% and 23.7%, respectively. Grade ≥2 late GI and GU toxicities were observed in 6.6% and 2.6% of patients, respectively. No grade 4 toxicity was observed.Hypofractionated stereotactic boost is effective and safely delivered for intermediate-risk prostate carcinoma after conventional radiation. Mild-term relapse-free survival and tolerance results are promising, and further follow-up is warranted to confirm the results at long term.ClinicalTrials.gov NCT01596816.

  5. Radiation-induced Genomic Instability and Radiation Sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Varnum, Susan M.; Sowa, Marianne B.; Kim, Grace J.; Morgan, William F.

    2013-01-19

    The obvious relationships between reactive oxygen and nitrogen species, mitochondrial dysfunction, inflammatory type responses and reactive chemokines and cytokines suggests a general stress response induced by ionizing radiation most likely leads to the non-targeted effects described after radiation exposure. We argue that true bystander effects do not occur in the radiation therapy clinic. But there is no question that effects outside the target volume do occur. These “out of field effects” are considered very low dose effects in the context of therapy. So what are the implications of non-targeted effects on radiation sensitivity? The primary goal of therapy is to eradicate the tumor. Given the genetic diversity of the human population, lifestyle and environment factors it is likely some combination of these will influence patient outcome. Non-targeted effects may contribute to a greater or lesser extent. But consider the potential situation involving a partial body exposure due to a radiation accident or radiological terrorism. Non-targeted effects suggest that the tissue at risk for demonstrating possible detrimental effects of radiation exposure might be greater than the volume actually irradiated.

  6. Basic reactions induced by radiation

    International Nuclear Information System (INIS)

    Charlesby, A.

    1980-01-01

    This paper summarises some of the basic reactions resulting from exposure to high energy radiation. In the initial stages energy is absorbed, but not necessarily at random, giving radical and ion species which may then react to promote the final chemical change. However, it is possible to intervene at intermediate stages to modify or reduce the radiation effect. Under certain conditions enhanced reactions are also possible. Several expressions are given to calculate radiation yield in terms of energy absorbed. Some analogies between radiation-induced reactions in polymers, and those studied in radiobiology are outlined. (author)

  7. Radiation-Induced Differentiation in Human Lung Fibroblast

    International Nuclear Information System (INIS)

    Park, Sa-Rah; Ahn, Ji-Yeon; Han, Young-Soo; Shim, Jie-Young; Yun, Yeon-Sook; Song, Jie-Young

    2007-01-01

    One of the most common tumors in many countries is lung cancer and patients with lung cancer may take radiotherapy. Although radiotherapy may have its own advantages, it can also induce serious problems such as acute radiation pneumonitis and pulmonary fibrosis. Pulmonary fibrosis is characterized by excessive production of α-SMA and accumulation of extracellular matrix (ECM) such as collagen and fibronectin. There has been a great amount of research about fibrosis but the exact mechanism causing the reaction is not elucidated especially in radiation-induced fibrosis. Until now it has been known that several factors such as transforming growth factor (TGF-β), tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) are related to fibrosis. Among them TGF-β with Smad signaling is known to be the main stream and other signaling molecules such as MAPK, ERK and JNK (3) also participates in the process. In addition to those above factors, it is thought that more diverse and complicate mechanisms may involve in the radiationinduced fibrosis. Therefore, to investigate the underlying mechanisms in radiation induced fibrosis, first of all, we confirmed whether radiation induces trans differentiation in human normal lung fibroblasts. Here, we suggest that not only TGF-β but also radiation can induce trans differentiation in human lung fibroblast WI-38 and IMR-90

  8. Classical spreading-fractionation, hyperfractionation, hypofractionation: let us attempt to be practical

    International Nuclear Information System (INIS)

    Cosset, J.M.; Baillet, F.

    1986-01-01

    The so-called classical spreading-fractionation (5 sessions of 2 Gy per week) was elaborated originally by the first generation of radiotherapists at the beginning of the century. It is a remarkable fact that even today the most up-to-date radiobiologists are in agreement that this regimen usually represents the best possible compromise between antitumoral efficacy and toxicity to healthy tissue. Hyperfractionation is still in the clinical trial stage with the aim of defining its precise place in clinical practice. At the present there is only one formal indication apart from within this framework: tumors with very rapid times for doubling in size, since hyperfractionation alone can deliver a high dose in a short period of time (accelerated treatment). Hypofractionation can be highly recommended for palliative treatment, because of its simplicity and efficacy. In contrast, when large size tumours (particularly digestive) are treated in patients with an elevated expected rate of recovery, this technique may provoke late complications and should, a priori, be avoided. For small size tumours however (ENT, breast) it would appear possible to elaborate hypofractio - nation protocols allowing local control to a similar degree to that obtained with the classical regimen, without significantly increasing late complications, on the condition that radiation parameters (dose, spread, fractionation) be cho - sen with the greatest care [fr

  9. Radiation-Induced Alopecia after Endovascular Embolization under Fluoroscopy

    Directory of Open Access Journals (Sweden)

    Vipawee Ounsakul

    2016-01-01

    Full Text Available Radiation-induced alopecia after fluoroscopically guided procedures is becoming more common due to an increasing use of endovascular procedures. It is characterized by geometric shapes of nonscarring alopecia related to the area of radiation. We report a case of a 46-year-old man presenting with asymptomatic, sharply demarcated rectangular, nonscarring alopecic patch on the occipital scalp following cerebral angiography with fistula embolization under fluoroscopy. His presentations were compatible with radiation-induced alopecia. Herein, we also report a novel scalp dermoscopic finding of blue-grey dots in a target pattern around yellow dots and follicles, which we detected in the lesion of radiation-induced alopecia.

  10. Radiation-induced neuropathies: collateral damage of improved cancer prognosis

    International Nuclear Information System (INIS)

    Pradat, Pierre-Francois; Maisonobe, Thierry; Psimaras, Dimitri; Lenglet, Timothee; Porcher, Raphael; Lefaix, J.L.; Delenian, S.

    2012-01-01

    Because of the improvement of cancer prognosis, long-term damages of treatments become a medical and public health problem. Among the iatrogenic complications, neurological impairment is crucial to consider since motor disability and pain have a considerable impact on quality of life of long cancer survivors. However, radiation-induced neuropathies have not been the focus of great attention. The objective of this paper is to provide an updated review about the radiation-induced lesions of the peripheral nerve system. Radiation-induced neuropathies are characterized by their heterogeneity in both symptoms and disease course. Signs and symptoms depend on the affected structures of the peripheral nerve system (nerve roots, nerve plexus or nerve trunks). Early-onset complications are often transient and late complications are usually progressive and associated with a poor prognosis. The most frequent and well known is delayed radiation-induced brachial plexopathy, which may follow breast cancer irradiation. Radiation-induced lumbosacral radiculoplexopathy is characterized by pure or predominant lower motor neuron signs. They can be misdiagnosed, confused with amyotrophic lateral sclerosis (ALS) or with leptomeningeal metastases since nodular MRI enhancement of the nerve roots of the cauda equina and increased cerebrospinal fluid protein content can be observed. In the absence of specific markers of the link with radiotherapy, the diagnosis of post-radiation neuropathy may be difficult. Recently, a posteriori conformal radiotherapy with 3D dosimetric reconstitution has been developed to link a precise anatomical site to unexpected excess irradiation. The importance of early diagnosis of radiation-induced neuropathies is underscored by the emergence of new disease-modifying treatments. Although the pathophysiology is not fully understood, it is already possible to target radiation-induced fibrosis but also associated factors such as ischemia, oxidative stress and

  11. Radiation induced mitotic delay and stimulation of growth

    International Nuclear Information System (INIS)

    Feldmann, A.

    1974-01-01

    The mechanisms responsible for the radiation induced mitotic delay and stimulation of growth are discussed in connection with the results of studies in Lemna minor and Lepidium sativum. The action of temperature seems to be of major importance. As many authors suggest that various chemical agents and slight intoxications also affect mitosis in a way similar to that induced by ionizing radiation, the radiation induced stimulation has lost its specific character and approaches might be found for further investigations of this phenomenon. (MG) [de

  12. Radiation-induced apoptosis in F9 teratocarcinoma cells

    International Nuclear Information System (INIS)

    Langley, R.E.; Palayoor, S.T.; Coleman, C.N.; Bump, E.A.

    1994-01-01

    We have found that F9 murine teratocarcinoma cells undergo morphological changes and internucleosomal DNA fragmentation characteristic of apoptosis after exposure to ionizing radiation. We studied the time course, radiation dose-response, and the effects of protein and RNA synthesis inhibitors on this process. The response is dose dependent in the range 2-12 Gy. Internucleosomal DNA fragmentation can be detected as early as 6 h postirradiation and is maximal by 48 h. Cycloheximide, a protein synthesis inhibitor, and 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole, an RNA synthesis inhibitor, both induced internucleosomal DNA fragmentation in the unirradiated cells and enhanced radiation-induced DNA fragmentation. F9 cells can be induced to differentiate into cells resembling endoderm with retinoic acid. After irradiation, differentiated F9 cells exhibit less DNA fragmentation than stem cells. This indicates that ionizing radiation can induce apoptosis in non-lymphoid tumours. We suggest that embryonic tumour cells may be particularly susceptible to agents that induce apoptosis. (Author)

  13. Radiation-induced apoptosis in F9 teratocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Langley, R E; Palayoor, S T; Coleman, C N; Bump, E A [Joint Center for Radiation Therapy and Dana Farber Cancer Inst., Boston (United States)

    1994-05-01

    We have found that F9 murine teratocarcinoma cells undergo morphological changes and internucleosomal DNA fragmentation characteristic of apoptosis after exposure to ionizing radiation. We studied the time course, radiation dose-response, and the effects of protein and RNA synthesis inhibitors on this process. The response is dose dependent in the range 2-12 Gy. Internucleosomal DNA fragmentation can be detected as early as 6 h postirradiation and is maximal by 48 h. Cycloheximide, a protein synthesis inhibitor, and 5,6-dichloro-1-[beta]-D-ribofuranosylbenzimidazole, an RNA synthesis inhibitor, both induced internucleosomal DNA fragmentation in the unirradiated cells and enhanced radiation-induced DNA fragmentation. F9 cells can be induced to differentiate into cells resembling endoderm with retinoic acid. After irradiation, differentiated F9 cells exhibit less DNA fragmentation than stem cells. This indicates that ionizing radiation can induce apoptosis in non-lymphoid tumours. We suggest that embryonic tumour cells may be particularly susceptible to agents that induce apoptosis. (Author).

  14. Safety and Efficacy of Bevacizumab With Hypofractionated Stereotactic Irradiation for Recurrent Malignant Gliomas

    International Nuclear Information System (INIS)

    Gutin, Philip H.; Iwamoto, Fabio M.; Beal, Kathryn; Mohile, Nimish A.; Karimi, Sasan; Hou, Bob L.; Lymberis, Stella; Yamada, Yoshiya; Chang, Jenghwa

    2009-01-01

    Purpose: Preclinical studies suggest that inhibition of vascular endothelial growth factor (VEGF) improves glioma response to radiotherapy. Bevacizumab, a monoclonal antibody against VEGF, has shown promise in recurrent gliomas, but the safety and efficacy of concurrent bevacizumab with brain irradiation has not been extensively studied. The objectives of this study were to determine the safety and activity of this combination in malignant gliomas. Methods and Materials: After prior treatment with standard radiation therapy patients with recurrent glioblastoma (GBM) and anaplastic gliomas (AG) received bevacizumab (10 mg/kg intravenous) every 2 weeks of 28-day cycles until tumor progression. Patients also received 30 Gy of hypofractionated stereotactic radiotherapy (HFSRT) in five fractions after the first cycle of bevacizumab. Results: Twenty-five patients (20 GBM, 5 AG; median age 56 years; median Karnofsky Performance Status 90) received a median of seven cycles of bevacizumab. One patient did not undergo HFSRT because overlap with prior radiotherapy would exceed the safe dose allowed to the optic chiasm. Three patients discontinued treatment because of Grade 3 central nervous system intratumoral hemorrhage, wound dehiscence, and bowel perforation. Other nonhematologic and hematologic toxicities were transient. No radiation necrosis was seen in these previously irradiated patients. For the GBM cohort, overall response rate was 50%, 6-month progression-free survival was 65%; median overall survival was 12.5 months, and 1-year survival was 54%. Discussion: Bevacizumab with HFSRT is safe and well tolerated. Radiographic responses, duration of disease control, and survival suggest that this regimen is active in recurrent malignant glioma.

  15. Radiation induced crosslinking of polytetrafluoroethylene

    International Nuclear Information System (INIS)

    Oshima, Akihiro; Tabata, Yoneho; Ikeda, Shigetoshi; Otsuhata, Kazushige; Kudoh, Hisaaki; Seguchi, Tadao.

    1995-01-01

    The Irradiation temperature effect on polytetrafluoroethylene (PTFE) from room temperature to 380degC was investigated by tensile test and thermal analysis. The behavior of tensile properties and changes of crystallinity on irradiation indicated the formation of a network structure in PTFE by radiation induced crosslinking in inert gas in the molten state just above the melting temperature of PTFE (327degC). The crosslinked PTFE showed a much improved radiation resistance in an atmospheric radiation field. (author)

  16. Study of radiation-induced chromosomal aberrations

    International Nuclear Information System (INIS)

    Wolfring, E.

    2004-06-01

    A method for determining chromosomal aberrations was established for the purpose of examining the relative biological effectiveness (RBE) of photon radiation with respect to mammary epithelium cells. Cells were exposed to 25 kV X-radiation and to 200 kV X-radiation for comparison and the resulting concentrations of chromosomal aberrations were compared. The RBE M value for radiation-induced fragmentation was found to be 4.2 ± 2.4, while the RBE M value for radiation-induced generation of dicentric chromosomes was found to be 0.5 ± 0.5. In addition to the evaluation of chromosomal aberrations the number of cell cycles undergone by the cells was monitored by means of BrDU staining. As expected, the proportion of cells which underwent more than one cell cycle following exposure to 5 Gy was very low in both cases, amounting to 1.9% (25 kV) and 3.2 (200 kV). Non-radiated cells yielded control values of 26.0% and 12.6%, suggesting variations in external conditions from day to day

  17. Cell cycle arrest induced by radiation

    International Nuclear Information System (INIS)

    Okaichi, Yasuo; Matsumoto, Hideki; Ohnishi, Takeo

    1994-01-01

    It is known that various chemical reactions, such as cell cycle arrest, DNA repair and cell killing, can occur within the cells when exposed to ionizing radiation and ultraviolet radiation. Thus protein dynamics involved in such chemical reactions has received considerable attention. In this article, cell cycle regulation is first discussed in terms of the G2/M-phase and the G1/S-phase. Then, radiation-induced cell cycle arrest is reviewed. Cell cycle regulation mechanism involved in the G2 arrest, which is well known to occur when exposed to radiation, has recently been investigated using yeasts. In addition, recent study has yielded a noticeable finding that the G1 arrest can occur with intracellular accumulation of p53 product following ionization radiation. p53 is also shown to play an extremely important role in both DNA repair and cell killing due to DNA damage. Studies on the role of genes in protein groups induced by radiation will hold promise for the elucidation of cell cycle mechanism. (N.K.) 57 refs

  18. Control of radiation-induced diarrhea with cholestyramine

    International Nuclear Information System (INIS)

    Heusinkveld, R.S.; Manning, M.R.; Aristizabal, S.A.

    1978-01-01

    Cholestyramine is a non-absorbable ion-exchange resin which specifically binds bile salts. We have treated seven patients with acute or chronic radiation-induced diarrhea that was refractory to the usual methods of control with cholestyramine. In each case, the diarrhea was controlled with cholestyramine. This observation supports previous experimental work with animals which indicated that bile salts contribute to the genesis of radiation-induced diarrhea. Cholestyramine is well-tolerated, but should not be administered with certain oral medications. The results of this small series are preliminary, but point the way toward a more extensive clinical trial to define the usefulness of cholestyramine in the treatment of refractory acute or chronic radiation-induced diarrhea

  19. Involvement of prostaglandins and histamine in radiation-induced temperature responses in rats

    International Nuclear Information System (INIS)

    Kandasamy, S.B.; Hunt, W.A.

    1990-01-01

    Exposure of rats to 1-15 Gy of gamma radiation induced hyperthermia, whereas exposure to 20-150 Gy produced hypothermia. Since radiation exposure induced the release of prostaglandins (PGs) and histamine, the role of PGs and histamine in radiation-induced temperature changes was examined. Radiation-induced hyper- and hypothermia were antagonized by pretreatment with indomethacin, a cyclooxygenase inhibitor. Intracerebroventricular administration of PGE2 and PGD2 induced hyper- and hypothermia, respectively. Administration of SC-19220, a specific PGE2 antagonist, attenuated PGE2- and radiation-induced hyperthermia, but it did not antagonize PGD2- or radiation-induced hypothermia. Consistent with an apparent role of histamine in hypothermia, administration of disodium cromoglycate (a mast cell stabilizer), mepyramine (H1-receptor antagonist), or cimetidine (H2-receptor antagonist) attenuated PGD2- and radiation-induced hypothermia. These results suggest that radiation-induced hyperthermia is mediated via PGE2 and that radiation-induced hypothermia is mediated by another PG, possibly PGD2, via histamine

  20. Molecular epidemiology of radiation-induced carcinogenesis

    International Nuclear Information System (INIS)

    Trosko, J.E.

    1996-01-01

    The role of ionizing radiation in carcinogenesis is discussed. Every cell contains proto-oncogenes, which if damaged may lead to cell transformation. Every cell also contains tumor suppressor genes, which guard against transformation. Thus, transformation would seem to require a double injury to the DNA in a cell. Ionizing radiation is known to be a relatively weak mutagen, but a good clastogen (inducer of chromosome breaks, deletions and rearrangements). Ionizing radiation may therefore be a 'promoter' of cancer, i.e. a stimulant of the clonal expansion of transformed cells, if it kills enough cells to induce compensatory hyperplasia - i.e. rapid growth of cells. Ionizing radiation may be a 'progressor', if it deactivates tumor suppressor genes tending to suppress the growth of existing clones of transformed cells resulting from any of numerous causes. It may therefore be an oversimplification to say that radiation causes cancer; rather, it seems to be a weak initiator, an indirect promoter, and a late-stage progressor. 2 figs

  1. Radiation-induced tumors of the nervous system

    International Nuclear Information System (INIS)

    Bernstein, M.; Laperriere, N.

    1991-01-01

    Therapeutic and nontherapeutic ionizing radiation has long been recognized as a putative carcinogenic agent, but the evidence that radiation causes tumors is circumstantial at worst and statistically significant at best. There are no distinct histological, biochemical, cytogenetic, or clinical criteria that can be used to determine if an individual tumor was caused directly by previous irradiation of the anatomic area. Additional supportive evidence for radiation-induced tumors includes a position correlation between radiation dose and tumor incidence (usually in the low dose range) and experimental induction of the same neoplasm in appropriate animal models. even if these criteria are fulfilled, coincidental development of a second tumor can never be discounted in an individual patient, particularly if there is an underlying diathesis to develop multiple tumors of different histology, such as in Recklinghausen's disease, or if there is an strong family history for the development of neoplastic disease. In this paper, the authors critically evaluate the available evidence to support the hypothesis that radiation induces tumors in the nervous system. The current concepts of radiation carcinogenesis are discussed and are followed by a discussion of animal data and clinical experience in humans. Finally, a brief discussion on treatment of radiation-induced nervous system tumors is presented

  2. Multi-Institutional Phase II Study of High-Dose Hypofractionated Proton Beam Therapy in Patients With Localized, Unresectable Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

    Science.gov (United States)

    Hong, Theodore S; Wo, Jennifer Y; Yeap, Beow Y; Ben-Josef, Edgar; McDonnell, Erin I; Blaszkowsky, Lawrence S; Kwak, Eunice L; Allen, Jill N; Clark, Jeffrey W; Goyal, Lipika; Murphy, Janet E; Javle, Milind M; Wolfgang, John A; Drapek, Lorraine C; Arellano, Ronald S; Mamon, Harvey J; Mullen, John T; Yoon, Sam S; Tanabe, Kenneth K; Ferrone, Cristina R; Ryan, David P; DeLaney, Thomas F; Crane, Christopher H; Zhu, Andrew X

    2016-02-10

    To evaluate the efficacy and safety of high-dose, hypofractionated proton beam therapy for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). In this single-arm, phase II, multi-institutional study, 92 patients with biopsy-confirmed HCC or ICC, determined to be unresectable by multidisciplinary review, with a Child-Turcotte-Pugh score (CTP) of A or B, ECOG performance status of 0 to 2, no extrahepatic disease, and no prior radiation received 15 fractions of proton therapy to a maximum total dose of 67.5 Gy equivalent. Sample size was calculated to demonstrate > 80% local control (LC) defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 criteria at 2 years for HCC patients, with the parallel goal of obtaining acceptable precision for estimating outcomes for ICC. Eighty-three patients were evaluable: 44 with HCC, 37 with ICC, and two with mixed HCC/ICC. The CTP score was A for 79.5% of patients and B for 15.7%; 4.8% of patients had no cirrhosis. Prior treatment had been given to 31.8% of HCC patients and 61.5% of ICC patients. The median maximum dimension was 5.0 cm (range, 1.9 to 12.0 cm) for HCC patients and 6.0 cm (range, 2.2 to 10.9 cm) for ICC patients. Multiple tumors were present in 27.3% of HCC patients and in 12.8% of ICC patients. Tumor vascular thrombosis was present in 29.5% of HCC patients and in 28.2% of ICC patients. The median dose delivered to both HCC and ICC patients was 58.0 Gy. With a median follow-up among survivors of 19.5 months, the LC rate at 2 years was 94.8% for HCC and 94.1% for ICC. The overall survival rate at 2 years was 63.2% for HCC and 46.5% ICC. High-dose hypofractionated proton therapy demonstrated high LC rates for HCC and ICC safely, supporting ongoing phase III trials of radiation in HCC and ICC. © 2015 by American Society of Clinical Oncology.

  3. Characterization of radiation-induced Apoptosis in rodent cell lines

    International Nuclear Information System (INIS)

    Guo, Min; Chen, Changhu; Ling, C.C.

    1997-01-01

    For REC:myc(ch1), Rat1 and Rat1:myc b cells, we determined the events in the development of radiation-induced apoptosis to be in the following order: cell division followed by chromatin condensation, membrane blebbing, loss of adhesion and the uptake of vital dye. Experimental data which were obtained using 4 He ions of well defined energies and which compared the dependence of apoptosis and clonogenic survival on 4 He range strongly suggested that in our cells both apoptosis and loss of clonogenic survival resulted from radiation damage to the cell nucleus. Corroboratory evidence was that BrdU incorporation sensitized these cells to radiation-induced apoptosis. Comparing the dose response for apoptosis and the clonogenic survival curves for Rat1 and Rat1:myc b cells, we concluded that radiation-induced cell inactivation as assayed by clonogenic survival, and that a modified linear-quadratic model, proposed previously, modeled such a contribution effectively. In the same context, the selective increase in radiation-induced apoptosis. Comparing the dose response for apoptosis and the clonogenic survival curves for Rat1 and Rat1:myc b cells, we concluded that radiation-induced apoptosis contributed to the overall radiation-induced cell inactivation as assayed by clonogenic survival, and that a modified linear-quadratic model, proposed previously, modeled such a contribution effectively. In the same context, the selective increase in radiation-induced apoptosis during late S and G 2 phases reduced the relative radioresistance observed for clonogenic survival during late S and G 2 phases. 30 refs., 8 figs

  4. Interaction of alpha radiation with thermally-induced defects in silicon

    International Nuclear Information System (INIS)

    Ali, Akbar; Majid, Abdul

    2008-01-01

    The interaction of radiation-induced defects created by energetic alpha particles and thermally-induced defects in silicon has been studied using a Deep Level Transient Spectroscopy (DLTS) technique. Two thermally-induced defects at energy positions E c -0.48 eV and E c -0.25 eV and three radiation-induced defects E2, E3 and E5 have been observed. The concentration of both of the thermally-induced defects has been observed to increase on irradiation. It has been noted that production rates of the radiation-induced defects are suppressed in the presence of thermally-induced defects. A significant difference in annealing characteristics of thermally-induced defects in the presence of radiation-induced defects has been observed compared to the characteristics measured in pre-irradiated samples

  5. Radiation-induced damage of membranes

    International Nuclear Information System (INIS)

    Yonei, Shuji

    1977-01-01

    An outline of membranous structure was stated, and radiation-induced damage of membranes were surveyed. By irradiation, permeability of membranes, especially passive transportation mechanism, was damaged, and glycoprotein in the surface layers of cells and the surface layer structures were changed. The intramembranous damage was induced by decrease of electrophoresis of nuclear mambranes and a quantitative change of cytochrome P450 of microsomal membranes of the liver, and peroxidation of membranous lipid and SH substitute damage of membranous protein were mentioned as the mechanism of membranous damage. Recovery of membranous damage depends on radiation dose and temperature, and membranous damage participates largely in proliferation death. (tsunoda, M.)

  6. Protection against radiation-induced performance decrement in mice

    International Nuclear Information System (INIS)

    Mukherjee, S.K.; Pant, Kanchan; Goel, H.C.; Jain, Viney

    1997-01-01

    Recognizing that there is lack of information on the effects of low-level ionizing radiations and the modifying role of radioprotectors, an attempt has been made in this study to explore the relationship between impairment of spatial learning and low level of radiation exposure. A radial arm maze was utilised to evaluate radiation-induced behavioural alterations and performance decrement in mice. Immediately after whole body exposure to gamma radiation (absorbed dose, 1 Gy) significant perturbations in the learned behaviour of the animals were observed. The regular control movement became irregular and the food consumption time was reduced appreciably (40%). Recovery took place in four days. If diltiazem (7 mg/kg b.w.), a Ca 2+ channel blocker and a radioprotector, was administered i.p. 20-30 min prior to irradiation, radiation-induced behavioural abnormalities were reduced. Mechanisms underlying protection by diltiazem against radiation-induced performance decrement observed in the present study need to be investigated. (author). 23 refs., 2 figs

  7. Radiation-Induced Second Cancer Risk Estimates From Radionuclide Therapy

    Science.gov (United States)

    Bednarz, Bryan; Besemer, Abigail

    2017-09-01

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

  8. WE-F-304-01: Overview of the Working Group On Stereotactic Body Radiation Therapy (WGSBRT)

    International Nuclear Information System (INIS)

    Yorke, E.

    2015-01-01

    Stereotactic Body Radiation Therapy (SBRT) was introduced clinically more than twenty years ago, and many subsequent publications have reported safety and efficacy data. The AAPM Working Group on Biological Effects of Hypofractionated Radiotherapy/SBRT (WGSBRT) extracted published treatment outcomes data from extensive literature searches to summarize and construct tumor control probability (TCP) and normal tissue complication probability (NTCP) models for six anatomical regions: Cranial, Head and Neck, Thoracic, Abdominal, Pelvic, and Spinal. In this session, we present the WGSBRT’s work for cranial sites, and recurrent head and neck cancer. From literature-based data and associated models, guidelines to aid with safe and effective hypofractionated radiotherapy treatment are being determined. Further, the ability of existing and proposed radiobiological models to fit these data is considered as to the ability to distinguish between the linear-quadratic and alternative radiobiological models such as secondary cell death from vascular damage, immunogenic, or bystander effects. Where appropriate, specific model parameters are estimated. As described in “The lessons of QUANTEC,” (1), lack of adequate reporting standards continues to limit the amount of useful quantitative information that can be extracted from peer-reviewed publications. Recommendations regarding reporting standards are considered, to enable such reviews to achieve more complete characterization of clinical outcomes. 1 Jackson A, Marks LB, Bentzen SM, Eisbruch A, Yorke ED, Ten Haken RK, Constine LS, Deasy JO. The lessons of QUANTEC: recommendations for reporting and gathering data on dose-volume dependencies of treatment outcome. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S155–60. Learning Objectives: Describe the techniques, types of cancer and dose schedules used in treating recurrent H&N cancers with SBRT List the radiobiological models that compete with the linear-quadratic model

  9. WE-F-304-01: Overview of the Working Group On Stereotactic Body Radiation Therapy (WGSBRT)

    Energy Technology Data Exchange (ETDEWEB)

    Yorke, E. [Memorial Sloan-Kettering Cancer Center (United States)

    2015-06-15

    Stereotactic Body Radiation Therapy (SBRT) was introduced clinically more than twenty years ago, and many subsequent publications have reported safety and efficacy data. The AAPM Working Group on Biological Effects of Hypofractionated Radiotherapy/SBRT (WGSBRT) extracted published treatment outcomes data from extensive literature searches to summarize and construct tumor control probability (TCP) and normal tissue complication probability (NTCP) models for six anatomical regions: Cranial, Head and Neck, Thoracic, Abdominal, Pelvic, and Spinal. In this session, we present the WGSBRT’s work for cranial sites, and recurrent head and neck cancer. From literature-based data and associated models, guidelines to aid with safe and effective hypofractionated radiotherapy treatment are being determined. Further, the ability of existing and proposed radiobiological models to fit these data is considered as to the ability to distinguish between the linear-quadratic and alternative radiobiological models such as secondary cell death from vascular damage, immunogenic, or bystander effects. Where appropriate, specific model parameters are estimated. As described in “The lessons of QUANTEC,” (1), lack of adequate reporting standards continues to limit the amount of useful quantitative information that can be extracted from peer-reviewed publications. Recommendations regarding reporting standards are considered, to enable such reviews to achieve more complete characterization of clinical outcomes. 1 Jackson A, Marks LB, Bentzen SM, Eisbruch A, Yorke ED, Ten Haken RK, Constine LS, Deasy JO. The lessons of QUANTEC: recommendations for reporting and gathering data on dose-volume dependencies of treatment outcome. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S155–60. Learning Objectives: Describe the techniques, types of cancer and dose schedules used in treating recurrent H&N cancers with SBRT List the radiobiological models that compete with the linear-quadratic model

  10. Radiation induced changes in the airway - anaesthetic implications ...

    African Journals Online (AJOL)

    Radiation induced changes in the airway - anaesthetic implications: case report. Mallika Balakrishnan, Renju Kuriakose, Rachel Cherian Koshy. Abstract. Radiation induces a variety of changes in the airway that can potentially lead to difficult intubation. Osteoradionecrosis (ORN) of the mandible, a severe consequence of ...

  11. Poor outcome in radiation-induced constrictive pericarditis

    International Nuclear Information System (INIS)

    Karram, T.; Rinkevitch, D.; Markiewicz, W.

    1993-01-01

    The purpose was to compare the outcome of patients with radiation-induced constrictive pericarditis versus patients with constiction due to another etiology. Twenty patients with constrictive pericarditis were seen during 1975-1986 at a single medical center. Six had radiation-induced constrictive pericarditis (Group A). The etiology was idiopathic in ten subjects and secondary to carcinomatous encasement, chronic renal failure, purulent infection and tuberculosis in one patient each (Group B, N = 14). Meang age was 53.4 ± 15.5 years. Extensive pericardiectomy was performed in 3/6 Group A and 13/14 Group B patients. All Group A patients died, 4 weeks - 11 years post-diagnosis (median = 10 months). Two Group A patients died suddenly, one died post-operatively of respiratory failure, another of pneumonia and two of recurrent carcinoma. Thirteen Group B patients are alive (median follow-up = 72 months). The only death in this group was due to metastatic cancer. The poor outcome with radiation-induced constriction is probably multi-factorial. Poor surgical outcome is to be expected in patients with evidence of recurrent tumor, high-dose irradiation, pulmonary fibrosis or associated radiation-induced myocardinal, valvular or coronary damage

  12. Poor outcome in radiation-induced constrictive pericarditis

    Energy Technology Data Exchange (ETDEWEB)

    Karram, T.; Rinkevitch, D.; Markiewicz, W. (Technion Medical School, Haifa (Israel))

    1993-01-15

    The purpose was to compare the outcome of patients with radiation-induced constrictive pericarditis versus patients with constiction due to another etiology. Twenty patients with constrictive pericarditis were seen during 1975-1986 at a single medical center. Six had radiation-induced constrictive pericarditis (Group A). The etiology was idiopathic in ten subjects and secondary to carcinomatous encasement, chronic renal failure, purulent infection and tuberculosis in one patient each (Group B, N = 14). Meang age was 53.4 [+-] 15.5 years. Extensive pericardiectomy was performed in 3/6 Group A and 13/14 Group B patients. All Group A patients died, 4 weeks - 11 years post-diagnosis (median = 10 months). Two Group A patients died suddenly, one died post-operatively of respiratory failure, another of pneumonia and two of recurrent carcinoma. Thirteen Group B patients are alive (median follow-up = 72 months). The only death in this group was due to metastatic cancer. The poor outcome with radiation-induced constriction is probably multi-factorial. Poor surgical outcome is to be expected in patients with evidence of recurrent tumor, high-dose irradiation, pulmonary fibrosis or associated radiation-induced myocardinal, valvular or coronary damage.

  13. Radiation induced pesticidal microbes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Yup; Lee, Y. K.; Kim, J. S.; Kim, J. K.; Lee, S. J.; Lim, D. S

    2001-01-01

    To isolate pesticidal microbes against plant pathogenic fungi, 4 strains of bacteria(K1. K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 12 kinds of fungi. Specific proteins and the specific transcribed genes were found from the YS1 and its radiation-induced mutants. And knock-out mutants of antifungal activity were derived by transposon mutagenesis. From these knock-out mutants, the antifungal activity related genes and its modification by gamma-ray radiation are going to be studied. These results suggested that radiation could be an useful tool for the induction of functional mutants.

  14. Radiation induced pesticidal microbes

    International Nuclear Information System (INIS)

    Kim, Ki Yup; Lee, Y. K.; Kim, J. S.; Kim, J. K.; Lee, S. J.; Lim, D. S.

    2001-01-01

    To isolate pesticidal microbes against plant pathogenic fungi, 4 strains of bacteria(K1. K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 12 kinds of fungi. Specific proteins and the specific transcribed genes were found from the YS1 and its radiation-induced mutants. And knock-out mutants of antifungal activity were derived by transposon mutagenesis. From these knock-out mutants, the antifungal activity related genes and its modification by gamma-ray radiation are going to be studied. These results suggested that radiation could be an useful tool for the induction of functional mutants

  15. 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.

  16. Cataracts induced by microwave and ionizing radiation

    International Nuclear Information System (INIS)

    Lipman, R.M.; Tripathi, B.J.; Tripathi, R.C.

    1988-01-01

    Microwaves most commonly cause anterior and/or posterior subcapsular lenticular opacities in experimental animals and, as shown in epidemiologic studies and case reports, in human subjects. The formation of cataracts seems to be related directly to the power of the microwave and the duration of exposure. The mechanism of cataractogenesis includes deformation of heat-labile enzymes, such as glutathione peroxide, that ordinarily protect lens cell proteins and membrane lipids from oxidative damage. Oxidation of protein sulfhydryl groups and the formation of high-molecular-weight aggregates cause local variations in the orderly structure of the lens cells. An alternative mechanism is thermoelastic expansion through which pressure waves in the aqueous humor cause direct physical damage to the lens cells. Cataracts induced by ionizing radiation (e.g., X-rays and gamma rays) usually are observed in the posterior region of the lens, often in the form of a posterior subcapsular cataract. Increasing the dose of ionizing radiation causes increasing opacification of the lens, which appears after a decreasing latency period. Like cataract formation by microwaves, cataractogenesis induced by ionizing radiation is associated with damage to the lens cell membrane. Another possible mechanism is damage to lens cell DNA, with decreases in the production of protective enzymes and in sulfur-sulfur bond formation, and with altered protein concentrations. Until further definitive conclusions about the mechanisms of microwaves and ionizing radiation induced cataracts are reached, and alternative protective measures are found, one can only recommend mechanical shielding from these radiations to minimize the possibility of development of radiation-induced cataracts. 74 references

  17. Hypofractionated stereotactic radiotherapy combined with topotecan in recurrent malignant glioma

    International Nuclear Information System (INIS)

    Wurm, Reinhard E.; Kuczer, David A.; Schlenger, Lorenz; Matnjani, Gesa; Scheffler, Dirk; Cosgrove, Vivian P.; Ahlswede, Julia; Woiciechowsky, Christian; Budach, Volker

    2006-01-01

    Purpose: To assess hypofractionated stereotactic radiotherapy (H-SRT) with concurrent topotecan in patients with recurrent malignant glioma. Methods and Materials: Between February 1998 and December 2001, 25 patients with recurrent malignant glioma were treated in a phase I-II study (8 females and 17 males; median age, 45 years; range, 11-66 years; median Karnofsky performance status, 80%, range, 50-100%; median Mini Mental Standard Examination score, 25 points; range, 10-30 points). Of the 25 patients, 20% had World Health Organization Grade III and 80% World Health Organization Grade IV glioma. All patients had been treated previously by external beam radiotherapy with 54.4 Gy in 34 fractions twice daily, at least 6 h apart, within 3.5 weeks or 60 Gy in 30 fractions within 6 weeks. In addition, 84% had already received at least one chemotherapy regimen for recurrence. The median H-SRT dose at the 80% isodose was 25 Gy, and the maximal dose was 30 Gy delivered in five to six fractions on consecutive days. Topotecan (1.1 mg/m 2 /d) was given as a continuous i.v. infusion during H-SRT. Depending on the toxicity and compliance, patients received an additional 48 topotecan courses. Results: For all patients, the actuarial median progression-free survival was 10.5 months (range, 1.4-47.8 months), the median functional survival was 12.6 months (range, 1.6-49.5 months), and the median overall survival was 14.5 months (range, 3-56.4 months). Twelve percent of patients developed presumed adverse radiation effects (Radiation Therapy Oncology Group Grade 2). According to the Common Toxicity Criteria, version 2.0, no topotecan-related Grade 4 toxicity was noted. Grade 3 neutropenia was documented after 14 and Grade 3 thrombopenia after 12 courses. Conclusion: H-SRT with topotecan is feasible and well-tolerated in patients with recurrent high-grade glioma and results in similar survival compared with other repeat treatment modalities

  18. Peculiarities of radiation induced craniopharyngioma

    Energy Technology Data Exchange (ETDEWEB)

    Sataev, N.M. (Uzbekskij Nauchno-Issledovatel' skij Inst. Onkologii i Radiologii, Tashkent (USSR))

    1982-03-01

    Due to intracranial implantation of a radiosource in rabbit brain craniopharyngioma appeared. Its specific feature is grandular differentiation of embryonal epithelium of residuals of hypophysical (craniopharyngial) passage and the presence of focuses of blood vessel tumor degeneration of hemangioma type in its stroma. It is suggested that radiation craniopharyngioma is developed along the way of epigenetic changes of cellular elements of embryonal epithelium induced by radiation.

  19. Peculiarities of radiation induced craniopharyngioma

    International Nuclear Information System (INIS)

    Sataev, N.M.

    1982-01-01

    Due to intracranial implantation of a radiosource in rabbit brain craniopharyngioma appeared. Its specific feature is grandular differentiation of embryonal epithelium of residuals of hypophysical (craniopharyngial) passage and the presence of focuses of blood vessel tumor degeneration of hemangioma type in its stroma. It is suggested that radiation craniopharyngioma is developed along the way of epigenetic changes of cellular elements of embryonal epithelium induced by radiation

  20. Radiation and desiccation response motif mediates radiation induced gene expression in D. radiodurans

    International Nuclear Information System (INIS)

    Anaganti, Narasimha; Basu, Bhakti; Apte, Shree Kumar

    2015-01-01

    Deinococcus radiodurans is an extremophile that withstands lethal doses of several DNA damaging agents such as gamma irradiation, UV rays, desiccation and chemical mutagens. The organism responds to DNA damage by inducing expression of several DNA repair genes. At least 25 radiation inducible gene promoters harbour a 17 bp palindromic sequence known as radiation and desiccation response motif (RDRM) implicated in gamma radiation inducible gene expression. However, mechanistic details of gamma radiation-responsive up-regulation in gene expression remain enigmatic. The promoters of highly radiation induced genes ddrB (DR0070), gyrB (DR0906), gyrA (DR1913), a hypothetical gene (DR1143) and recA (DR2338) from D. radiodurans were cloned in a green fluorescence protein (GFP)-based promoter probe shuttle vector pKG and their promoter activity was assessed in both E. coli as well as in D. radiodurans. The gyrA, gyrB and DR1143 gene promoters were active in E. coli although ddrB and recA promoters showed very weak activity. In D. radiodurans, all the five promoters were induced several fold following 6 kGy gamma irradiation. Highest induction was observed for ddrB promoter (25 fold), followed by DR1143 promoter (15 fold). The induction in the activity of gyrB, gyrA and recA promoters was 5, 3 and 2 fold, respectively. To assess the role of RDRM, the 17 bp palindromic sequence was deleted from these promoters. The promoters devoid of RDRM sequence displayed increase in the basal expression activity, but the radiation-responsive induction in promoter activity was completely lost. The substitution of two conserved bases of RDRM sequence yielded decreased radiation induction of PDR0070 promoter. Deletion of 5 bases from 5'-end of PDR0070 RDRM increased basal promoter activity, but radiation induction was completely abolished. Replacement of RDRM with non specific sequence of PDR0070 resulted in loss of basal expression and radiation induction. The results demonstrate that

  1. Radiation-induced brain damage in children

    International Nuclear Information System (INIS)

    Oi, Shizuo; Kokunai, Takashi; Ijichi, Akihiro; Matsumoto, Satoshi; Raimondi, A.J.

    1990-01-01

    The nature and sequence of the radiation-induced changes in the brain were studied postmortem in 34 children with glioma, 22 of whom underwent central nervous system radiation therapy. Twenty received whole-brain or whole-neuroaxis radiation at a total mean dosage of 4063 cGy. Brain tissue alternations were analyzed histologically by means of various staining methods, including immunohistochemical techniques. The histological features of irradiated brains were compared with those of non-irradiated brains. Microscopic findings included demyelination (seven cases), focal necrosis (six cases), cortical atrophy (four cases), endothelial proliferation (four cases), and telangiectatic vascular proliferation with vascular thickening and oozing of a thick fluid (one case). Such findings were rare in non-irradiated patients. Demyelination was observed earliest in a patient who died 5 months after radiation therapy and was more common after 9 months. Focal necrosis was first observed 9 months post-irradiation but was more advanced and extensive after 1 year. Calcified foci were found only after 60 months. Various vascular changes such as vascular thickening and thrombosis suggested ischemic insult to the brain as a late effect of radiation injury. The results of this study suggest that the immature brain may be more sensitive to radiation than is the adult brain, and that the manifestations of radiation-induced injury depend on the time elapsed after irradiation. (author)

  2. Radiation-induced xerostomia in a patient with nasopharyngeal ...

    African Journals Online (AJOL)

    OBJECTIVE: This study reports a case of radiation-induced xerstomia in a patient with nasopharyngeal cancer, to emphasize the need for prompt oral care to prevent untoward effects of xerostomia and to improve patients' quality of life. CASE REPORT: A 60 year old man diagnosed of radiation-induced xerostomia, after 6 ...

  3. Pelvic nodal dose escalation with prostate hypofractionation using conformal avoidance defined (H-CAD) intensity modulated radiation therapy

    International Nuclear Information System (INIS)

    Hong, Theodore S.; Tome, Wolfgang A.; Jaradat, Hazim; Raisbeck, Bridget M.; Ritter, Mark A.

    2006-01-01

    The management of prostate cancer patients with a significant risk of pelvic lymph node involvement is controversial. Both whole pelvis radiotherapy and dose escalation to the prostate have been linked to improved outcome in such patients, but it is unclear whether conventional whole pelvis doses of only 45-50 Gy are optimal for ultimate nodal control. The purpose of this study is to examine the dosimetric and clinical feasibility of combining prostate dose escalation via hypofractionation with conformal avoidance-based IMRT (H-CAD) dose escalation to the pelvic lymph nodes. One conformal avoidance and one conventional plan were generated for each of eight patients. Conformal avoidance-based IMRT plans were generated that specifically excluded bowel, rectum, and bladder. The prostate and lower seminal vesicles (PTV 70) were planned to receive 70 Gy in 2.5 Gy/fraction while the pelvic lymph nodes (PTV 56) were to concurrently receive 56 Gy in 2 Gy/fraction. The volume of small bowel receiving >45 Gy was restricted to 300 ml or less. These conformal avoidance plans were delivered using helical tomotherapy or LINAC-based IMRT with daily imaging localization. All patients received neoadjuvant and concurrent androgen deprivation with a planned total of two years. The conventional, sequential plans created for comparison purposes for all patients consisted of a conventional 4-field pelvic box prescribed to 50.4 Gy (1.8 Gy/fraction) followed by an IMRT boost to the prostate of 25.2 Gy (1.8 Gy/fraction) yielding a final prostate dose of 75.6 Gy. For all plans, the prescription dose was to cover the target structure. Equivalent uniform dose (EUD) analyses were performed on all targets and dose-volume histograms (DVH) were displayed in terms of both physical and normalized total dose (NTD), i.e. dose in 2 Gy fraction equivalents. H-CAD IMRT plans were created for and delivered to all eight patients. Analysis of the H-CAD plans demonstrates prescription dose coverage of >95

  4. The probabilities of one- and multi-track events for modeling radiation-induced cell kill

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Uwe; Vasi, Fabiano; Besserer, Juergen [University of Zuerich, Department of Physics, Science Faculty, Zurich (Switzerland); Radiotherapy Hirslanden, Zurich (Switzerland)

    2017-08-15

    In view of the clinical importance of hypofractionated radiotherapy, track models which are based on multi-hit events are currently reinvestigated. These models are often criticized, because it is believed that the probability of multi-track hits is negligible. In this work, the probabilities for one- and multi-track events are determined for different biological targets. The obtained probabilities can be used with nano-dosimetric cluster size distributions to obtain the parameters of track models. We quantitatively determined the probabilities for one- and multi-track events for 100, 500 and 1000 keV electrons, respectively. It is assumed that the single tracks are statistically independent and follow a Poisson distribution. Three different biological targets were investigated: (1) a DNA strand (2 nm scale); (2) two adjacent chromatin fibers (60 nm); and (3) fiber loops (300 nm). It was shown that the probabilities for one- and multi-track events are increasing with energy, size of the sensitive target structure, and dose. For a 2 x 2 x 2 nm{sup 3} target, one-track events are around 10,000 times more frequent than multi-track events. If the size of the sensitive structure is increased to 100-300 nm, the probabilities for one- and multi-track events are of the same order of magnitude. It was shown that target theories can play a role for describing radiation-induced cell death if the targets are of the size of two adjacent chromatin fibers or fiber loops. The obtained probabilities can be used together with the nano-dosimetric cluster size distributions to determine model parameters for target theories. (orig.)

  5. Ionizing radiation induced genomic instability and its relation to radiation carcinogenesis

    International Nuclear Information System (INIS)

    Wang Zhongwen

    2000-01-01

    There are widespread testimonies that the genomic instability induced by ionizing irradiation exits in mammal and its vitro cells. Genomic instability can enhance the frequency of genetic changes among the progeny of the original irradiated cells. In the radiation-leukemogenesis, there is no significant difference between controls and CBA/H mouses of PPI (preconception patent irradiation), but the offsprings of the PPI recipients show a different character (shorter latent period and higher incidence) after an extra γ-radiation. The radiation-induced genomic instability may get the genome on the verge of mutation and lead to carcinogens following mutation of some critical genes. The genomic instability, as the early event of initiation of carcinomas, may be play a specific or unique role

  6. Radiation-induced valvular heart disease.

    Science.gov (United States)

    Gujral, Dorothy M; Lloyd, Guy; Bhattacharyya, Sanjeev

    2016-02-15

    Radiation to the mediastinum is a key component of treatment with curative intent for a range of cancers including Hodgkin's lymphoma and breast cancer. Exposure to radiation is associated with a risk of radiation-induced heart valve damage characterised by valve fibrosis and calcification. There is a latent interval of 10-20 years between radiation exposure and development of clinically significant heart valve disease. Risk is related to radiation dose received, interval from exposure and use of concomitant chemotherapy. Long-term outlook and the risk of valve surgery are related to the effects of radiation on mediastinal structures including pulmonary fibrosis and pericardial constriction. Dose prediction models to predict the risk of heart valve disease in the future and newer radiation techniques to reduce the radiation dose to the heart are being developed. Surveillance strategies for this cohort of cancer survivors at risk of developing significant heart valve complications are required. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  7. Effectiveness of the herbal medicine daikenchuto for radiation-induced enteritis.

    Science.gov (United States)

    Takeda, Takashi; Kamiura, Shouji; Kimura, Tadashi

    2008-07-01

    Radiation-induced enteritis is a serious clinical problem for which there is currently no recommended standard management. Daikenchuto (DKT) is a Japanese herbal medicine that has been used to treat adhesive bowel obstruction in Japan. This report describes a patient with radiation-induced enteritis whose clinical symptoms were much improved by treatment with DKT. The patient was administered DKT, a traditional Japanese herbal formula, orally (2.5 g 3 times daily). Abdominal distention was evaluated objectively with computed tomography. Gastrointestinal symptoms associated with radiation-induced enteritis were controlled successfully with DKT treatment. DKT treatment may be useful for the management of radiation-induced enteritis.

  8. Hypofractionation for radiotherapy of prostate cancer using a low alfa/beta ratio - possible reasons for concerns? An example of five dimensional radiotherapy

    International Nuclear Information System (INIS)

    Lennernaes, Bo; Nilsson, Sten; Levitt, Seymour

    2011-01-01

    It is very attractive, due to the assumed low alfa/beta ratio of prostate cancer (PC), to construct new treatment schedules for prostate cancer using only a few large fractions of radiation (hypofractionation). This will widen the therapeutic window since the ratio for PC might be lower than that of the organs at risk (OAR). PC is an extremely variable disease and often contains both highly and poorly differentiated cells. It is reasonable to assume that different cells have different patterns of radiosensitivity, i.e. alfa/beta ratios and proliferation. In this study we will simulate the effect on the outcome of the treatment with different fractionations and different ratios. Material and methods. In this simulation we use an extension of the Linear Quadratic (LQ)/Biological Effective Dose (BED) formula called the dose volume inhomogeneity corrected BED (DVIC-BED). In the formula the tumour volume is divided in 50 subvolumes (step of 2%) and it is possible to calculate the relative effect of the treatment with different ratios (1.5, 4 and 6.5) in different subvolumes. Results. The simulations demonstrate that only a small portion (5-10%) of cells with a higher ratio will dramatically change the effect of the treatment. Increasing the total dose can compensate this, but this will on the other hand increase the dose to the OAR and also the risk for severe side effects. Conclusion. These simulations highlight possible reasons for concerns about the use of hypofractionation for pathologically heterogeneous tumours, such as prostate cancer, and also demonstrate the need for testing new treatment schedules using both high and low ratios

  9. Kinetics of radiation-induced segregation in ternary alloys

    International Nuclear Information System (INIS)

    Lam, N.O.; Kumar, A.; Wiedersich, H.

    1982-01-01

    Model calculations of radiation-induced segregation in ternary alloys have been performed, using a simple theory. The theoretical model describes the coupling between the fluxes of radiation-induced defects and alloying elements in an alloy A-B-C by partitioning the defect fluxes into those occurring via A-, B-, and C-atoms, and the atom fluxes into those taking place via vacancies and interstitials. The defect and atom fluxes can be expressed in terms of concentrations and concentration gradients of all the species present. With reasonable simplifications, the radiation-induced segregation problem can be cast into a system of four coupled partial-differential equations, which can be solved numerically for appropriate initial and boundary conditions. Model calculations have been performed for ternary solid solutions intended to be representative of Fe-Cr-Ni and Ni-Al-Si alloys under various irradiation conditions. The dependence of segregation on both the alloy properties and the irradiation variables, e.g., temperature and displacement rate, was calculated. The sample calculations are in good qualitative agreement with the general trends of radiation-induced segregation observed experimentally

  10. Seven cases of radiation-induced cutaneous squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Sugita, Kazunari; Yamamoto, Osamu; Suenaga, Yoshinori [Univ. of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan). School of Medicine

    2000-09-01

    We report 7 cases of radiation-induced skin cancer. The diagnosis was based on the history of radiotherapy for benign skin diseases (5 cases) and of occupational exposures to medical doctors (2 cases). All cases were squamous cell carcinomas which arose from chronic radiodermatitis. The estimated latent period of these tumors ranged from 6 to 64 years, with an average of 29.9 years. After surgical treatments of the lesions, no local recurrences were observed in all cases. Benign skin diseases had sometimes been treated with low-energy radiation before the 1960s. Considering the estimated latent period, the peak time point of developing risk of radiation-induced skin cancer by such treatment has been already passed, however, the danger of it should not be ignored in future. In association with multiplicity of radiation usage, occupational exposure of radiation may develop the risk of occurrence of skin cancer in future. Therefore, we should recognize that radiation-induced skin cancer is not in the past. In the cases of chronic skin diseases showing warty keratotic growth, erosion and ulcer, we should include chronic radio-dermatitis in the differential diagnosis. It is necessary to recall all patients about the history of radiotherapy or radiation exposure. Rapid histopathological examination is mandatory because of the suspicion of radiation-induced skin cancer. (author)

  11. Seven cases of radiation-induced cutaneous squamous cell carcinoma

    International Nuclear Information System (INIS)

    Sugita, Kazunari; Yamamoto, Osamu; Suenaga, Yoshinori

    2000-01-01

    We report 7 cases of radiation-induced skin cancer. The diagnosis was based on the history of radiotherapy for benign skin diseases (5 cases) and of occupational exposures to medical doctors (2 cases). All cases were squamous cell carcinomas which arose from chronic radiodermatitis. The estimated latent period of these tumors ranged from 6 to 64 years, with an average of 29.9 years. After surgical treatments of the lesions, no local recurrences were observed in all cases. Benign skin diseases had sometimes been treated with low-energy radiation before the 1960s. Considering the estimated latent period, the peak time point of developing risk of radiation-induced skin cancer by such treatment has been already passed, however, the danger of it should not be ignored in future. In association with multiplicity of radiation usage, occupational exposure of radiation may develop the risk of occurrence of skin cancer in future. Therefore, we should recognize that radiation-induced skin cancer is not in the past. In the cases of chronic skin diseases showing warty keratotic growth, erosion and ulcer, we should include chronic radio-dermatitis in the differential diagnosis. It is necessary to recall all patients about the history of radiotherapy or radiation exposure. Rapid histopathological examination is mandatory because of the suspicion of radiation-induced skin cancer. (author)

  12. Membrane phospholipids and radiation-induced death of mammalian cells

    International Nuclear Information System (INIS)

    Wolters, H.

    1987-01-01

    Radiation-induced cell killing is generally believed to be a consequence of residual DNA damage or damage that is mis-repaired. However, besides this DNA damage, damage to other molecules or structures of the cell may be involved in the killing. Especially membranes have been suggested as a determinant in cellular radiosensitivity. In this thesis experiments are described, dealing with the possible involvement of membranes in radiation-induced killing of mammalian cells. A general treatise of membrane structure is followed by information concerning deleterious effects of radiation on membranes. Consequences of damage to structure and function of membranes are reviewed. Thereafter evidence relating to the possible involvement of membranes in radiation-induced cell killing is presented. (Auth.)

  13. Radiation-induced alternative transcripts as detected in total and polysome-bound mRNA.

    Science.gov (United States)

    Wahba, Amy; Ryan, Michael C; Shankavaram, Uma T; Camphausen, Kevin; Tofilon, Philip J

    2018-01-02

    Alternative splicing is a critical event in the posttranscriptional regulation of gene expression. To investigate whether this process influences radiation-induced gene expression we defined the effects of ionizing radiation on the generation of alternative transcripts in total cellular mRNA (the transcriptome) and polysome-bound mRNA (the translatome) of the human glioblastoma stem-like cell line NSC11. For these studies, RNA-Seq profiles from control and irradiated cells were compared using the program SpliceSeq to identify transcripts and splice variations induced by radiation. As compared to the transcriptome (total RNA) of untreated cells, the radiation-induced transcriptome contained 92 splice events suggesting that radiation induced alternative splicing. As compared to the translatome (polysome-bound RNA) of untreated cells, the radiation-induced translatome contained 280 splice events of which only 24 were overlapping with the radiation-induced transcriptome. These results suggest that radiation not only modifies alternative splicing of precursor mRNA, but also results in the selective association of existing mRNA isoforms with polysomes. Comparison of radiation-induced alternative transcripts to radiation-induced gene expression in total RNA revealed little overlap (about 3%). In contrast, in the radiation-induced translatome, about 38% of the induced alternative transcripts corresponded to genes whose expression level was affected in the translatome. This study suggests that whereas radiation induces alternate splicing, the alternative transcripts present at the time of irradiation may play a role in the radiation-induced translational control of gene expression and thus cellular radioresponse.

  14. Non-targeted bystander effects induced by ionizing radiation

    International Nuclear Information System (INIS)

    Morgan, William F.; Sowa, Marianne B.

    2007-01-01

    Radiation-induced bystander effects refer to those responses occurring in cells that were not subject to energy deposition events following ionizing radiation. These bystander cells may have been neighbors of irradiated cells, or physically separated but subject to soluble secreted signals from irradiated cells. Bystander effects have been observed in vitro and in vivo and for various radiation qualities. In tribute to an old friend and colleague, Anthony V. Carrano, who would have said 'well what are the critical questions that should be addressed, and so what?', we review the evidence for non-targeted radiation-induced bystander effects with emphasis on prevailing questions in this rapidly developing research field, and the potential significance of bystander effects in evaluating the detrimental health effects of radiation exposure

  15. Radiation-induced hondrosarcoma - a clinical case from our practice

    International Nuclear Information System (INIS)

    Marinova, L.; Georgiev, R.; Mihaylova, I.

    2013-01-01

    We present a clinical case of radiation - induced occipital extracerebral chondrosarcoma in 36 years old young man. The patient had undergone two brain operations 8 years ago due to oligodendroglioma in the left temporo - parietal area. These surgical interventions were partial and subtotal tumor extirpation, followed by local radiotherapy to the brain to a total dose of 56Gy. The necessity of immunohistochemistry (IHH) analysis for pathologic differential diagnosis in high grade brain and peripheral tumors was discussed. In this particular case a precise differential diagnosis between peripheral chondrosarcoma and Ewing sarcoma/pPNET is needed. important risk factors for the development of radiation-induced brain tumors and chondrosarcoma, extremely rarely diagnosed, was discussed. A very accurate precising of the treatment radiation dose is needed in young patients with malignant brain tumors, not only in the surrounding healthy brain tissues, but also in other tissues, such as skin, subcutaneous layer and bone. The exceeding of the radiation dose in the bone above 45-50 Gy, increases the risk of radiation - induced sarcoma with latent period over 8 years. Key words: Hondrosarcoma. Radiotherapy. Radiation-induced Sarcoma. Complex Treatment. Immunohistochemistry

  16. Bile acids in radiation-induced diarrhea

    International Nuclear Information System (INIS)

    Arlow, F.L.; Dekovich, A.A.; Priest, R.J.; Beher, W.T.

    1987-01-01

    Radiation-induced bowel disease manifested by debilitating diarrhea is an unfortunate consequence of therapeutic irradiation for pelvic malignancies. Although the mechanism for this diarrhea is not well understood, many believe it is the result of damage to small bowel mucosa and subsequent bile acid malabsorption. Excess amounts of bile acids, especially the dihydroxy components, are known to induce water and electrolyte secretion and increase bowel motility. We have directly measured individual and total bile acids in the stool samples of 11 patients with radiation-induced diarrhea and have found bile acids elevated two to six times normal in eight of them. Our patients with diarrhea and increased bile acids in their stools had prompt improvement when given cholestyramine. They had fewer stools and returned to a more normal life-style

  17. Ionizing radiation induces stemness in cancer cells.

    Directory of Open Access Journals (Sweden)

    Laura Ghisolfi

    Full Text Available The cancer stem cell (CSC model posits the presence of a small number of CSCs in the heterogeneous cancer cell population that are ultimately responsible for tumor initiation, as well as cancer recurrence and metastasis. CSCs have been isolated from a variety of human cancers and are able to generate a hierarchical and heterogeneous cancer cell population. CSCs are also resistant to conventional chemo- and radio-therapies. Here we report that ionizing radiation can induce stem cell-like properties in heterogeneous cancer cells. Exposure of non-stem cancer cells to ionizing radiation enhanced spherogenesis, and this was accompanied by upregulation of the pluripotency genes Sox2 and Oct3/4. Knockdown of Sox2 or Oct3/4 inhibited radiation-induced spherogenesis and increased cellular sensitivity to radiation. These data demonstrate that ionizing radiation can activate stemness pathways in heterogeneous cancer cells, resulting in the enrichment of a CSC subpopulation with higher resistance to radiotherapy.

  18. Specitic gene alterations in radiation-induced tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Joo Mee; Kang, Chang Mo; Lee, Seung Sook; Cho, Chul Koo; Bae, Sang Woo; Lee, Su Jae; Lee, Yun Sil [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2004-07-01

    To identify a set of genes involved in the development of radiation-induced tumorigenesis, we used DNA microarrays consisting of 1,176 mouse genes and compared expression profiles of radioresistant cells, designated NIH3T3-R1 and -R4. These cells were tumorigenic in a nude mouse grafting system, as compared to the parental NIH3T3 cells. Expressions of MDM2, CDK6 and CDC25B were found to increase more than 3-fold. Entactin protein levels were downregulated in NIH3T3-R1 and -R4 cells. Changes in expression genes were confirmed by reverse transcription-PCR or western blotting. When these genes were transfected to NIH3T3 cells, the CDC25B and MDM2 overexpressing NIH3T3 cells showed radioresistance, while 2 CDK6 overexpressing cells did not. In the case of entactin overexpressing NIH3T3-R1 or R-4 cells were still radioresistant. Furthermore, the CDC25B and MDM2 overexpressing cells grafted to nude mice, were tumorigenic. NIH3T3-R1 and R4 cells showed increased radiation-induced apoptosis, accompanied by faster growth rate, rather than and earlier radiation-induced G2/M phase arrest, suggesting that the radioresistance of NIH3T3-R1 and R4 cells was due to faster growth rate, rather than induction of apoptosis. In the case of MDM2 and CDC25B overexpressing cells, similar phenomena, such as increased apoptosis and faster growth rate, were shown. The above results, therefore, demonstrate involvement of CDC25B and MDM2 overexpression in radiation-induced tumorigenesis and provide novel targets for detection of radiation-induced carcinogenesis.

  19. Induced Compton-scattering effects in radiation-transport approximations

    International Nuclear Information System (INIS)

    Gibson, D.R. Jr.

    1982-02-01

    The method of characteristics is used to solve radiation transport problems with induced Compton scattering effects included. The methods used to date have only addressed problems in which either induced Compton scattering is ignored, or problems in which linear scattering is ignored. Also, problems which include both induced Compton scattering and spatial effects have not been considered previously. The introduction of induced scattering into the radiation transport equation results in a quadratic nonlinearity. Methods are developed to solve problems in which both linear and nonlinear Compton scattering are important. Solutions to scattering problems are found for a variety of initial photon energy distributions

  20. Simulating Space Radiation-Induced Breast Tumor Incidence Using Automata.

    Science.gov (United States)

    Heuskin, A C; Osseiran, A I; Tang, J; Costes, S V

    2016-07-01

    Estimating cancer risk from space radiation has been an ongoing challenge for decades primarily because most of the reported epidemiological data on radiation-induced risks are derived from studies of atomic bomb survivors who were exposed to an acute dose of gamma rays instead of chronic high-LET cosmic radiation. In this study, we introduce a formalism using cellular automata to model the long-term effects of ionizing radiation in human breast for different radiation qualities. We first validated and tuned parameters for an automata-based two-stage clonal expansion model simulating the age dependence of spontaneous breast cancer incidence in an unexposed U.S. We then tested the impact of radiation perturbation in the model by modifying parameters to reflect both targeted and nontargeted radiation effects. Targeted effects (TE) reflect the immediate impact of radiation on a cell's DNA with classic end points being gene mutations and cell death. They are well known and are directly derived from experimental data. In contrast, nontargeted effects (NTE) are persistent and affect both damaged and undamaged cells, are nonlinear with dose and are not well characterized in the literature. In this study, we introduced TE in our model and compared predictions against epidemiologic data of the atomic bomb survivor cohort. TE alone are not sufficient for inducing enough cancer. NTE independent of dose and lasting ∼100 days postirradiation need to be added to accurately predict dose dependence of breast cancer induced by gamma rays. Finally, by integrating experimental relative biological effectiveness (RBE) for TE and keeping NTE (i.e., radiation-induced genomic instability) constant with dose and LET, the model predicts that RBE for breast cancer induced by cosmic radiation would be maximum at 220 keV/μm. This approach lays the groundwork for further investigation into the impact of chronic low-dose exposure, inter-individual variation and more complex space radiation

  1. Construction of radiation - induced metastasis model in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Kuk; Jang, Su Jin; Kang, Sung Wook; Kim, Jae Sung; Hwang, Sang Gu; Kang, Joo Hyun [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2011-05-15

    In treatment of cancer, distant metastases are important limiting factor because an estimated 50% of all cancer patients will develop metastases, and the metastases are major causing of cancer treatment failure. Recently a few reports indicated {gamma}-radiation induced an increase of invasiveness of several cancer cells. In this study, we had tried to show the possibility that radiation could also induce metastasis in vivo system. To prove our hypothesis, we constructed primary tumor by using C6-TL transfectant cell line expressing HSV1-tk and firefly luciferase (fLuc), and then {gamma}-radiation was treated to xenografts locally. Treatment of {gamma}-radiation to primary C6-TL xenografts of mice reduced size of xenografts and elongated survival of mice than those of mock control mice. But we also show that {gamma}-radiation treatment was followed by the growth of dormant metastases in various organs including lung and intestine after 2-4 weeks of {gamma}-radiation treatment. When bioluminescence imaging indicated growth of tumor in organs in mice, we sacrificed the mice and repeat acquired bioluminescence imaging after repeatedly. These images presented tumor growth locations exactly in organs. Because metastatic tumor candidates have morphology of foci, biopsies were performed for histological analysis or PCR analysis to confirm metastases. In most foci, histological analysis indicated several features of typical cancer tissue and PCR analysis showed present of fLuc gene in metastases. Detection of fLuc gene in metastases indicated these foci were originated from primary C6-TL xenografts, and the results suggest that {gamma}-radiation could promote metastasis in vivo as well as in vitro system. Although we need to understand changes of intracellular signaling or physiological phenomena of the radiation-induced metastasis yet, these results also imply that {gamma}-radiation treatment only to cancer patients need to pay attention carefully, and development of new

  2. Immunohistochemical study of p53 overexpression in radiation-induced colon cancers

    International Nuclear Information System (INIS)

    Minami, Kazunori; Hayashi, Nobuyuki; Mokarim, A.; Matsuzaki, Sumihiro; Ito, Masahiro; Sekine, Ichiro.

    1998-01-01

    The expressions of p53 and proliferating cell nuclear antigen (PCNA) were studied immunohistochemically from paraffin sections of 7 cases (9 lesions) of radiation-induced colon cancer and 42 cases of spontaneous colon cancer. Age distribution of radiation-induced and spontaneous colon cancer were 68.1 years (range, 56 to 77 years) and 67.4 years (range, 31 to 85 years), respectively. Among the radiation-induced colon cancers, there were 3 lesions of mucinous carcinoma (33%), a much higher than found for spontaneous mucinous cancer. Immunohistochemically, p53 protein expression was detected in 7/9 (78%) of radiation-induced cancers and in 23/42 (55%) of spontaneous colon cancers. χ 2 analysis found no significant differences between radiation-induced and spontaneous colon cancers in age distribution or p53-positive staining for frequency, histopathology, or Dukes'' classification. In radiation colitis around the cancers including aberrant crypts, spotted p53 staining and abnormal and scattered PCNA-positive staining were observed. In histologically normal cells, p53 staining was almost absent and PCNA-positive staining was regularly observed in the lower half of the crypt. In radiation colitis including aberrant glands, cellular proliferation increased and spotted p53 expression was observed. This study suggests that radiation colitis and aberrant glands might possess malignant potential and deeply associate with carcinogenesis of radiation-induced colon cancer. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Cury, Fabio L., E-mail: fabio.cury@muhc.mcgill.ca [Department of Radiation Oncology, McGill University Health Centre, Montreal, QC (Canada); Duclos, Marie [Department of Radiation Oncology, McGill University Health Centre, Montreal, QC (Canada); Aprikian, Armen [Department of Urology, McGill University Health Centre, Montreal, QC (Canada); Patrocinio, Horacio [Department of Medical Physics, McGill University Health Centre, Montreal, QC (Canada); Kassouf, Wassim [Department of Urology, McGill University Health Centre, Montreal, QC (Canada); Shenouda, George; Faria, Sergio; David, Marc; Souhami, Luis [Department of Radiation Oncology, McGill University Health Centre, Montreal, QC (Canada)

    2012-03-15

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

  4. Application of controlled radiation-induced degradation in polymers: less exploited aspect of radiation processing of polymers

    International Nuclear Information System (INIS)

    Haji Saeid, M.; Guven, O.

    2007-01-01

    Industrial use of ionizing radiation treatment has been most successful in applications related to polymeric materials. The polymer, plastics and rubber industries have benefited from the unique advantages of ionizing radiation since its inception as an industrial tool to modify their properties and manufacture novel materials with value addition to the end product. The established and emerging applications of electron beam processing of polymers are based on the well known ultimate effects of ionizing radiation on polymers namely, crosslinking, curing, grafting and chain scissioning. Radiation-induced crosslinking dominates most applications, whereas the chain scissioning effect is much less explored and currently limited to radiation-induced degradation of Teflon, cellulose and polypropylene. The controlling of radiation-induced degradation for achieving a target average molecular weight or distribution has been evaluated for some polysaccharides, biopolymers and waste inner tubes whereas mitigation of the degradative effects of radiation has been analyzed from the point of view of using certain stabilizers, copolymers and annealing at an appropriate temperature. Several new or highly specialized techniques such as positron annihilation lifetime spectroscopy. Rutherford backscattering, elastic recoil detection analysis and solid waste NMR spectroscopy and gas chromatography-mass spectroscopy have been applied to the study or radiation-induced degradation. New information has been collected on the morphological changes associated with radiation-induced degradation processes, including chain scission, oxidation and free volume alteration. The IAEA coordinated research project (CRP) on Controlling of Degradation Effects in Radiation Processing of Polymers dealt with the role and importance of using ionizing radiation in controlling properties of natural and synthetic polymers through its degradative effect. This paper provides a summary of most important results

  5. A report on radiation-induced gliomas

    International Nuclear Information System (INIS)

    Salvati, M.; Artico, M.; Caruso, R.; Rocchi, G.; Orlando, E.R.; Nucci, F.

    1991-01-01

    Radiation-induced gliomas are uncommon, with only 73 cases on record to date. The disease that most frequently occasioned radiation therapy has been acute lymphoblastic leukemia (ALL). Three more cases are added here, two after irradiation for ALL and one after irradiation for tinea capitis. In a review of the relevant literature, the authors stress the possibility that the ALL-glioma and the retinoblastoma-glioma links point to syndromes in their own right that may occur without radiation therapy.56 references

  6. Epigenetic Analysis of Heavy-ion Radiation Induced Bystander Effects in Mice

    Science.gov (United States)

    Zhang, Meng; Sun, Yeqing; Cui, Changna; Xue, Bei

    Abstract: Radiation-induced bystander effect was defined as the induction of damage in neighboring non-hit cells by signals released from directly-irradiated cells. Recently, low dose of high LET radiation induced bystander effects in vivo have been reported more and more. It has been indicated that radiation induced bystander effect was localized not only in bystander tissues but also in distant organs. Genomic, epigenetic and proteomics plays significant roles in regulating heavy-ion radiation stress responses in mice. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male Balb/c and C57BL mice were exposed head-only to 40, 200, 2000mGy dose of (12) C heavy-ion radiation, while the rest of the animal body was shielded. Directly radiation organ ear and the distant organ liver were detected on 1h, 6h, 12h and 24h after radiation, respectively. Methylation-sensitive amplification polymorphism (MSAP) was used to monitor the level of polymorphic genomic DNA methylation changed with dose and time effects. The results show that heavy-ion irradiated mouse head could induce genomic DNA methylation changes significantly in both the directly radiation organ ear and the distant organ liver. The percent of DNA methylation changes were time-dependent and tissue-specific. Demethylation polymorphism rate was highest separately at 1 h in 200 mGy and 6 h in 2000 mGy after irradiation. The global DNA methylation changes tended to occur in the CG sites. The results illustrated that genomic methylation changes of heavy ion radiation-induced bystander effect in liver could be obvious 1 h after radiation and achieved the maximum at 6 h, while the changes could recover gradually at 12 h. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in both directly radiation organ ear and distant organ liver. Moreover, our findings are important to understand the molecular mechanism of

  7. Radiation-induced conductivity of polynaphthoyl benzimidazole

    Energy Technology Data Exchange (ETDEWEB)

    Tiutnev, A P; Berlin, A M; Saenko, V S; Rusanov, A L; Korshak, V V

    1985-01-01

    The nonstationary radiation-induced conductivity of polynaphthoyl benzimidazole, synthesized by single-stage high-temperature catalytic polycondensation, is investigated experimentally. It is shown that the radiation-induced conductivity of this material is characterized by an anomalous (non-Gaussian) transfer of excess charge carriers. The activation energy of the delayed component (0.1 ms after pulse termination) is determined to be 0.12 eV; the volt-ampere characteristic of this component is nonlinear, with the coefficient of nonlinearity increasing with the intensity of the external electric field. Experimental results are interpreted on the basis of the phenomenological theory of jump conductivity proposed by Zviagin. 15 references.

  8. Ubiquitin-dependent system controls radiation induced apoptosis

    International Nuclear Information System (INIS)

    Delic, J.; Magdelenat, H.; Glaisner, S.; Magdelenat, H.; Maciorowski, Z.

    1997-01-01

    The selective proteolytic pathway, dependent upon 'N-end rule' protein recognition/ubiquitination and on the subsequent proteasome dependent processing of ubiquitin conjugates, operates in apoptosis induced by γ-irradiation. The proteasome inhibitor peptide aldehyde, MG132, efficiently induced apoptosis and was also able (at doses lower than those required for apoptosis induction) to potentiate apoptosis induced by DNA damage. Its specificity is suggested by the induction of the ubiquitin (UbB and UbC) and E1 (ubiquitin activating enzyme) genes and by an altered ubiquitination pattern. More selectively, a di-peptide competitor of the 'N-end rule' of ubiquitin dependent protein processing inhibited radiation induced apoptosis. This inhibition is also followed by an altered ubiquitination pattern and by activation of Poly (ADP-ribose) polymerase (PARP). These data strongly suggest that early apoptosis radiation induced events are controlled by ubiquitin-dependent proteolytic processing. (author)

  9. Is serum level of CC chemokine ligand 18 a biomarker for the prediction of radiation induced lung toxicity (RILT)?

    Science.gov (United States)

    Gkika, Eleni; Vach, Werner; Adebahr, Sonja; Schimek-Jasch, Tanja; Brenner, Anton; Brunner, Thomas Baptist; Kaier, Klaus; Prasse, Antje; Müller-Quernheim, Joachim; Grosu, Anca-Ligia; Zissel, Gernot; Nestle, Ursula

    2017-01-01

    The CC chemokine ligand 18 (CCL18) is produced by alveolar macrophages in patients with fibrosing lung disease and its concentration is increased in various fibrotic lung diseases. Furthermore CCL18 is elevated in several malignancies as it is produced by tumor associated macrophages. In this study we aimed to analyze the role of CCL18 as a prognostic biomarker for the development of early radiation induced lung toxicity (RILT), i.e. radiation pneumonitis after thoracic irradiation and its significance in the course of the disease. Sixty seven patients were enrolled prospectively in the study. Patients were treated with irradiation for several thoracic malignancies (lung cancer, esophageal cancer, thymoma), either with conventionally fractionated or hypo-fractionated radiotherapy. The CCL18 serum levels were quantified with ELISA (enzyme-linked immunosorbent assay) at predefined time points: before, during and at the end of treatment as well as in the first and second follow-up. Treatment parameters and functional tests were also correlated with the development of RILT.Fifty three patients were evaluable for this study. Twenty one patients (39%) developed radiologic signs of RILT Grade >1 but only three of them (5.6%) developed clinical symptoms (Grade 2). We could not find any association between the different CCL18 concentrations and a higher incidence of RILT. Statistical significant factors were the planning target volume (odds ratio OR: 1.003, p = 0.010), the volume of the lung receiving > 20 Gy (OR: 1.132 p = 0.004) and age (OR: 0.917, p = 0.008). There was no association between serial CCL18 concentrations with tumor response and overall survival.In our study the dosimetric parameters remained the most potent predictors of RILT. Further studies are needed in order to estimate the role of CCL18 in the development of early RILT.

  10. Is serum level of CC chemokine ligand 18 a biomarker for the prediction of radiation induced lung toxicity (RILT?

    Directory of Open Access Journals (Sweden)

    Eleni Gkika

    Full Text Available The CC chemokine ligand 18 (CCL18 is produced by alveolar macrophages in patients with fibrosing lung disease and its concentration is increased in various fibrotic lung diseases. Furthermore CCL18 is elevated in several malignancies as it is produced by tumor associated macrophages. In this study we aimed to analyze the role of CCL18 as a prognostic biomarker for the development of early radiation induced lung toxicity (RILT, i.e. radiation pneumonitis after thoracic irradiation and its significance in the course of the disease. Sixty seven patients were enrolled prospectively in the study. Patients were treated with irradiation for several thoracic malignancies (lung cancer, esophageal cancer, thymoma, either with conventionally fractionated or hypo-fractionated radiotherapy. The CCL18 serum levels were quantified with ELISA (enzyme-linked immunosorbent assay at predefined time points: before, during and at the end of treatment as well as in the first and second follow-up. Treatment parameters and functional tests were also correlated with the development of RILT.Fifty three patients were evaluable for this study. Twenty one patients (39% developed radiologic signs of RILT Grade >1 but only three of them (5.6% developed clinical symptoms (Grade 2. We could not find any association between the different CCL18 concentrations and a higher incidence of RILT. Statistical significant factors were the planning target volume (odds ratio OR: 1.003, p = 0.010, the volume of the lung receiving > 20 Gy (OR: 1.132 p = 0.004 and age (OR: 0.917, p = 0.008. There was no association between serial CCL18 concentrations with tumor response and overall survival.In our study the dosimetric parameters remained the most potent predictors of RILT. Further studies are needed in order to estimate the role of CCL18 in the development of early RILT.

  11. MO-FG-BRA-05: Dosimetric and Radiobiological Validation of Respiratory Gating in Conventional and Hypofractionated Radiotherapy of the Lung: Effect of Dose, Dose Rate, Gating Window and Breathing Pattern

    Energy Technology Data Exchange (ETDEWEB)

    Cervino, L; Soultan, D; Pettersson, N; Yock, A; Cornell, M; Aguilera, J; Murphy, J; Advani, S; Moiseenko, V [University of California, San Diego, La Jolla, CA (United States); Gill, B [British Columbia Cancer Agency, Vancouver, BC (Canada)

    2016-06-15

    Purpose: to evaluate the dosimetric and radiobiological consequences from having different gating windows, dose rates, and breathing patterns in gated VMAT lung radiotherapy. Methods: A novel 3D-printed moving phantom with central high and peripheral low tracer uptake regions was 4D FDG-PET/CT-scanned using ideal, patient-specific regular, and irregular breathing patterns. A scan of the stationary phantom was obtained as a reference. Target volumes corresponding to different uptake regions were delineated. Simultaneous integrated boost (SIB) 6 MV VMAT plans were produced for conventional and hypofractionated radiotherapy, using 30–70 and 100% cycle gating scenarios. Prescribed doses were 200 cGy with SIB to 240 cGy to high uptake volume for conventional, and 800 with SIB to 900 cGy for hypofractionated plans. Dose rates of 600 MU/min (conventional and hypofractionated) and flattening filter free 1400 MU/min (hypofractionated) were used. Ion chamber measurements were performed to verify delivered doses. Vials with A549 cells placed in locations matching ion chamber measurements were irradiated using the same plans to measure clonogenic survival. Differences in survival for the different doses, dose rates, gating windows, and breathing patterns were analyzed. Results: Ion chamber measurements agreed within 3% of the planned dose, for all locations, breathing patterns and gating windows. Cell survival depended on dose alone, and not on gating window, breathing pattern, MU rate, or delivery time. The surviving fraction varied from approximately 40% at 2Gy to 1% for 9 Gy and was within statistical uncertainty relative to that observed for the stationary phantom. Conclusions: Use of gated VMAT in PET-driven SIB radiotherapy was validated using ion chamber measurements and cell survival assays for conventional and hypofractionated radiotherapy.

  12. Radiation-induced cancer in Japan

    International Nuclear Information System (INIS)

    Yamashita, Shoji; Sekizuka, Eiichi; Yamashita, Hisao; Takami, Akira; Kubo, Atsushi

    2001-01-01

    Results of two questionnaire surveys on radiation-induced malignant tumors conducted in 1977 and 1984 in Japan are briefly summarized. A total of 234 universities and general hospitals (139 in 1977, and 95 in 1984) responded and provided data from 1945 to 1977 and from 1978 to 1984. The number of patients with benign disease who developed secondary malignant tumors following radiation therapy was 150 in the first survey (1977) and 86 in the second survey (1984). The underlying benign diseases of these patients included tuberculous lymphadenitis, skin disease, hemangioma, and thyroid disease, and the most frequent radiation-induced malignant tumors in these patients were malignant tumors of the pharynx (80), cancer of the larynx (26), malignant tumors of the thyroid gland (22), cancer of the esophagus (219), and skin cancer (21). In patients with head and neck diseases the highest correlation between underlying benign disease and radiation-induced malignant tumors was between cervical tuberculous lymphadenitis and tumors of the pharynx (67 patients), followed by cancer of the larynx (19), and malignant tumors of the thyroid gland (11). There were also correlations between thyroid disease and malignant tumors of the thyroid gland (8 patients), hemangioma and skin cancer (7), and skin disease and skin cancer (8). The ratio of the observed values to predicted values (O/E ratio) in these patients was highest for cancer of the pharynx (118), followed by cancer of the parotid gland (42), skin cancer (31), cancer of the esophagus (22), malignant tumors of the thyroid gland (21), and cancer of the larynx (16). The number of patients with malignant tumors who developed secondary malignant tumors following radiation therapy was 140 in 1977 and 108 in 1984, and the underlying malignant tumors in these patients included tumors of the uterus (106), breast (32), and head and neck (80). The most frequent secondary malignant tumors were soft tissue tumors, followed by leukemia, and

  13. Radiation induced liver disease: A clinical update

    International Nuclear Information System (INIS)

    Benson, R.; Madan, R.; Chander, S.; Kilambi, R.

    2016-01-01

    Radiation-induced liver disease (RILD) or radiation hepatitis is a sub-acute form of liver injury due to radiation. It is one of the most dreaded complications of radiation which prevents radiation dose escalation and re irradiation for hepatobiliary or upper gastrointestinal malignancies. This complication should be kept in mind whenever a patient is planned for irradiation of these malignancies. Although, incidence of RILD is decreasing due to better knowledge of liver tolerance, improved investigation modalities and modern radiation delivery techniques, treatment options are still limited. In this review article, we have focussed on pathophysiology, risk factors, prevention and management of RILD

  14. Radiation-induced meningiomas in pediatric patients

    International Nuclear Information System (INIS)

    Moss, S.D.; Rockswold, G.L.; Chou, S.N.; Yock, D.; Berger, M.S.

    1988-01-01

    Radiation-induced meningiomas rarely have latency periods short enough from the time of irradiation to the clinical presentation of the tumor to present in the pediatric patient. Three cases of radiation-induced intracranial meningiomas in pediatric patients are presented. The first involved a meningioma of the right frontal region in a 10-year-old boy 6 years after the resection and irradiation of a 4th ventricular medulloblastoma. Review of our pediatric tumor cases produced a second case of a left temporal fossa meningioma presenting in a 15-year-old boy with a history of irradiation for retinoblastoma at age 3 years and a third case of a right frontoparietal meningioma in a 15-year-old girl after irradiation for acute lymphoblastic leukemia. Only three cases of meningiomas presenting in the pediatric age group after radiation therapy to the head were detected in our review of the literature

  15. Radiation-induced mutations and plant breeding

    International Nuclear Information System (INIS)

    Naqvi, S.H.M.

    1985-01-01

    Ionizing radiation could cause genetic changes in an organism and could modify gene linkages. The induction of mutation through radiation is random and the probability of getting the desired genetic change is low but can be increased by manipulating different parameters such as dose rate, physical conditions under which the material has been irradiated, etc. Induced mutations have been used as a supplement to conventional plant breeding, particularly for creating genetic variability for specific characters such as improved plant structure, pest and disease resistance, and desired changes in maturity period; more than 200 varieties of crop plants have been developed by this technique. The Pakistan Atomic Energy Commission has used this technique fruitfully to evolve better germplasm in cotton, rice, chickpea, wheat and mungbean; some of the mutants have become popular commercial varieties. This paper describes some uses of radiation induced mutations and the results achieved in Pakistan so far

  16. Radiation induced oral mucositis

    Directory of Open Access Journals (Sweden)

    P S Satheesh Kumar

    2009-01-01

    Full Text Available Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii who also received concomitant chemotherapy; (iii who received a total dose over 5,000 cGy; and (iv who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene

  17. Prevention of malignant seeding at drain sites after invasive procedures (surgery and/or thoracoscopy) by hypofractionated radiotherapy in patients with pleural mesothelioma

    International Nuclear Information System (INIS)

    Di Salvo, Maurizio; Gambaro, Giuseppina; Pagella, Simonetta; Manfredda, Iren e; Casadio, Caterina; Krengli, Marco

    2008-01-01

    Introduction. Literature data show that mesothelioma cells can implant along the surgical pathway of invasive procedures such as thoracotomy and thoracoscopy. We investigated the use of hypofractionated radiotherapy for preventing such malignant seeding. Material and methods. Thirty-two consecutive patients diagnosed with pleural mesothelioma were included in the present retrospective study. All patients underwent surgery and/or thoracoscopy for diagnosis, staging or talc pleurodesis. They were treated with electron external beam radiation therapy (21 Gy in 3 fractions over 1 week), directed to the surgical pathway after the invasive procedure. After completion of radiation treatment, 20 of 32 patients (63%) underwent chemotherapy. Results. After a mean follow-up of 13.6 months (range 3-41) from the end of radiation therapy, no patient had tumour progression in the treated area. The treatment was well tolerated, as only erythema grade I (Radiation Therapy Oncology Group, RTOG, scale) was noted in 11 patients. Seventeen patients died of disease with local progression after a mean survival time of 12.6 months (range 3-27); thirteen patients are alive with disease after a mean follow-up of 13.9 months (range 4-41); two patients are alive without evidence of disease after a mean follow-up of 16.50 months (range 6-27). Discussion. The present study shows the efficacy and safety of local radiotherapy in preventing malignant seeding after thoracoscopy in patients with pleural mesothelioma although larger prospective trials are probably still needed to validate this treatment approach

  18. Prevention of malignant seeding at drain sites after invasive procedures (surgery and/or thoracoscopy) by hypofractionated radiotherapy in patients with pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Di Salvo, Maurizio; Gambaro, Giuseppina; Pagella, Simonetta; Manfredda, Irene; Casadio, Caterina; Krengli, Marco (Radiotherapy, Univ. of Piemonte Orientale-Hospital Maggiore della Carit, Novara (Italy))

    2008-07-15

    Introduction. Literature data show that mesothelioma cells can implant along the surgical pathway of invasive procedures such as thoracotomy and thoracoscopy. We investigated the use of hypofractionated radiotherapy for preventing such malignant seeding. Material and methods. Thirty-two consecutive patients diagnosed with pleural mesothelioma were included in the present retrospective study. All patients underwent surgery and/or thoracoscopy for diagnosis, staging or talc pleurodesis. They were treated with electron external beam radiation therapy (21 Gy in 3 fractions over 1 week), directed to the surgical pathway after the invasive procedure. After completion of radiation treatment, 20 of 32 patients (63%) underwent chemotherapy. Results. After a mean follow-up of 13.6 months (range 3-41) from the end of radiation therapy, no patient had tumour progression in the treated area. The treatment was well tolerated, as only erythema grade I (Radiation Therapy Oncology Group, RTOG, scale) was noted in 11 patients. Seventeen patients died of disease with local progression after a mean survival time of 12.6 months (range 3-27); thirteen patients are alive with disease after a mean follow-up of 13.9 months (range 4-41); two patients are alive without evidence of disease after a mean follow-up of 16.50 months (range 6-27). Discussion. The present study shows the efficacy and safety of local radiotherapy in preventing malignant seeding after thoracoscopy in patients with pleural mesothelioma although larger prospective trials are probably still needed to validate this treatment approach.

  19. Induced Compton scattering effects in radiation transport approximations

    International Nuclear Information System (INIS)

    Gibson, D.R. Jr.

    1982-01-01

    In this thesis the method of characteristics is used to solve radiation transport problems with induced Compton scattering effects included. The methods used to date have only addressed problems in which either induced Compton scattering is ignored, or problems in which linear scattering is ignored. Also, problems which include both induced Compton scattering and spatial effects have not been considered previously. The introduction of induced scattering into the radiation transport equation results in a quadratic nonlinearity. Methods are developed to solve problems in which both linear and nonlinear Compton scattering are important. Solutions to scattering problems are found for a variety of initial photon energy distributions

  20. Radiation-induced pseudotumor following therapy for soft tissue sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Lacey F.; Kransdorf, Mark J. [Mayo Clinic, Department of Radiology, Jacksonville, FL (United States); Buskirk, Steven J. [Mayo Clinic, Department of Radiation Oncology, Jacksonville, FL (United States); O' Connor, Mary I. [Mayo Clinic, Department of Orthopedic Surgery, Jacksonville, FL (United States); Menke, David M. [Mayo Clinic, Department of Pathology, Jacksonville, FL (United States)

    2009-06-15

    The purpose of this study was to describe the prevalence and imaging appearance of radiation induced pseudotumors in patients following radiation therapy for extremity soft tissue sarcomas. We retrospectively reviewed the serial magnetic resonance (MR) images of 24 patients following radiation therapy for extremity soft tissue sarcomas. A total of 208 exams were reviewed (mean, 8.7 exams per patient) and included all available studies following the start of radiation therapy. Exams were analyzed for the identification of focal signal abnormalities within the surgical bed suggesting local tumor recurrence. Histopathologic correlation was available in nine patients suspected of having local tumor recurrence. Additional information recorded included patient demographics, tumor type and location, radiation type, and dose. The study group consisted of 12 men and 12 women, having an average age of 63 years (range, 39-88 years). Primary tumors were malignant fibrous histiocytoma (n = 13), leiomyosarcoma (n = 6), liposarcoma (n = 3), synovial sarcoma (n = 1), and extraskeletal chondrosarcoma (n = 1). All lesions were high-grade sarcomas, except for two myxoid liposarcomas. Average patient radiation dose was 5,658 cGy (range, 4,500-8,040 cGy). Average follow-up time was 63 months (range, 3-204 months). Focal signal abnormalities suggesting local recurrence were seen in nine (38%) patients. Three of the nine patients with these signal abnormalities were surgically proven to have radiation-induced pseudotumor. The pseudotumors developed between 11 and 61 months following the initiation of radiation therapy (mean, 38 months), with an average radiation dose of 5,527 cGy (range, 5,040-6,500 cGy). MR imaging demonstrated a relatively ill-defined ovoid focus of abnormal signal and intense heterogeneous enhancement with little or no associated mass effect. MR imaging of radiation-induced pseudotumor typically demonstrates a relatively ill-defined ovoid mass-like focus of intense

  1. Mechanistic issues for modeling radiation-induced segregation

    International Nuclear Information System (INIS)

    Simonen, E.P.; Bruemmer, S.M.

    1993-03-01

    Model calculations of radiation-induced chromium depletion and radiation-induced nickel enrichment at grain boundaries are compared to measured depletions and enrichments. The model is calibrated to fit chromium depletion in commercial purity 304 stainless steel irradiated in boiling water reactor (BWR) environments. Predicted chromium depletion profiles and the dose dependence of chromium concentration at grain boundaries are in accord with measured trends. Evaluation of chromium and nickel profiles in three neutron, and two ion, irradiation environments reveal significant inconsistencies between measurements and predictions

  2. Radiation induced genetic damage in Aspergillus nidulans

    International Nuclear Information System (INIS)

    Georgiou, J.T.

    1984-01-01

    The mechanism by which ionizing radiation induces genetic damage in haploid and diploid conidia of Aspergillus nidulans was investigated. Although the linear dose-response curves obtained following low LET irradiation implied a 'single-hit' action of radiation, high LET radiations were much more efficient than low LET radiations, which suggests the involvement of a multiple target system. It was found that the RBE values for non-disjunction and mitotic crossing-over were very different. Unlike mitotic crossing-over, the RBE values for non-disjunction were much greater than for cell killing. This suggests that non-disjunction is a particularly sensitive genetical endpoint that is brought about by damage to a small, probably non-DNA target. Radiosensitisers were used to study whether radiation acts at the level of the DNA or some other cellular component. The sensitisation to electrons and/or X-rays by oxygen, and two nitroimidazoles (metronidazole and misonidazole) was examined for radiation induced non-disjunction, mitotic crossing-over, gene conversion, point mutation and cell killing. It was found that these compounds sensitised the cells considerably more to genetic damage than to cell killing. (author)

  3. Mechanisms of radiation-induced neoplastic cell transformation

    Energy Technology Data Exchange (ETDEWEB)

    Yang, T.C.H.; Tobias, C.A.

    1984-04-01

    Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table.

  4. Mechanisms of radiation-induced neoplastic cell transformation

    International Nuclear Information System (INIS)

    Yang, T.C.H.; Tobias, C.A.

    1984-04-01

    Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table

  5. Radiation induced glioblastoma. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Naoki; Kayama, Takamasa; Sakurada, Kaori; Saino, Makoto; Kuroki, Akira [Yamagata Univ. (Japan). School of Medicine

    2000-05-01

    We report a surgical case of a 54-year-old woman with a radiation induced glioblastoma. At the age of 34, the patient was diagnosed to have a non-functioning pituitary adenoma. It was partially removed followed by 50 Gy focal irradiation with a 5 x 5 cm lateral opposed field. Twenty years later, she suffered from rapidly increasing symptoms such as aphasia and right hemiparesis. MRI showed a large mass lesion in the left temporal lobe as well as small mass lesions in the brain stem and the right medial temporal lobe. These lesions situated within the irradiated field. Magnetic resonance spectroscopy revealed relatively high lactate signal and decreased N-acetyl aspartate, choline, creatine and phosphocreatine signals. Increased lactate signal meant anaerobic metabolism that suggested the existence of a rapidly growing malignant tumor. Thus, we planned surgical removal of the left temporal lesion with the diagnosis of a radiation induced malignant glioma. The histological examination revealed a glioblastoma with radiation necrosis. MIB-1 staining index was 65%. Postoperatively, her symptoms improved, but she died from pneumonia 1 month after the surgery. A autopsy was obtained. The lesion of the left temporal lobe was found to have continuity to the lesion in the midbrain, the pons and the right temporal lobe as well. High MIB-1 staining index suggested that a radiation induced glioblastoma had high proliferative potential comparing with a de novo and secondary glioblastoma. (author)

  6. Indomethacin attenuation of radiation-induced hyperthermia does not modify radiation-induced motor hypoactivity

    Energy Technology Data Exchange (ETDEWEB)

    Ferguson, J.L.; Kandasamy, S.B.; Harris, A.H.; Davis, H.D.; Landauer, M.R. [Armed Forces Radiobiology Research Inst., Bethesda, MD (United States)

    1996-09-01

    Exposure of rats to 5-10 Gy of ionizing radiation produces hyperthermia and reduces motor activity. Previous studies suggested that radiation-induced hyperthermia results from a relatively direct action on the brain and is mediated by prostaglandins. To test the hypothesis that hypoactivity may be, in part, a thermoregulatory response to this elevation in body temperature, adult male rats were given indomethacin (0.0, 0.5, 1.0, and 3.0 mg/kg, intraperitoneally), a blocker of prostaglandin synthesis, and were either irradiated (LINAC 18.6 MeV (nominal) high-energy electrons, 10 Gy at 10 Gy/min, 2.8 {mu}sec pulses at 2 Hz) or sham-irradiated. The locomotor activity of all rats was then measured for 30 min in a photocell monitor for distance traveled and number of vertical movements. Rectal temperatures of irradiated rats administered vehicle only were elevated by 0.9{+-}0.2degC at the beginning and the end of the activity session. Although indomethacin, at the two higher doses tested, attenuated the hyperthermia in irradiated rats by 52-75%, it did not attenuate radiation-induced reductions in motor activity. These results indicate that motor hypoactivity after exposure to 10 Gy of high-energy electrons is not due to elevated body temperature or to the increased synthesis of prostaglandins. (author)

  7. Indomethacin attenuation of radiation-induced hyperthermia does not modify radiation-induced motor hypoactivity

    International Nuclear Information System (INIS)

    Ferguson, J.L.; Kandasamy, S.B.; Harris, A.H.; Davis, H.D.; Landauer, M.R.

    1996-01-01

    Exposure of rats to 5-10 Gy of ionizing radiation produces hyperthermia and reduces motor activity. Previous studies suggested that radiation-induced hyperthermia results from a relatively direct action on the brain and is mediated by prostaglandins. To test the hypothesis that hypoactivity may be, in part, a thermoregulatory response to this elevation in body temperature, adult male rats were given indomethacin (0.0, 0.5, 1.0, and 3.0 mg/kg, intraperitoneally), a blocker of prostaglandin synthesis, and were either irradiated (LINAC 18.6 MeV (nominal) high-energy electrons, 10 Gy at 10 Gy/min, 2.8 μsec pulses at 2 Hz) or sham-irradiated. The locomotor activity of all rats was then measured for 30 min in a photocell monitor for distance traveled and number of vertical movements. Rectal temperatures of irradiated rats administered vehicle only were elevated by 0.9±0.2degC at the beginning and the end of the activity session. Although indomethacin, at the two higher doses tested, attenuated the hyperthermia in irradiated rats by 52-75%, it did not attenuate radiation-induced reductions in motor activity. These results indicate that motor hypoactivity after exposure to 10 Gy of high-energy electrons is not due to elevated body temperature or to the increased synthesis of prostaglandins. (author)

  8. Radiation induces aerobic glycolysis through reactive oxygen species

    International Nuclear Information System (INIS)

    Zhong, Jim; Rajaram, Narasimhan; Brizel, David M.; Frees, Amy E.; Ramanujam, Nirmala; Batinic-Haberle, Ines; Dewhirst, Mark W.

    2013-01-01

    Background and purpose: Although radiation induced reoxygenation has been thought to increase radiosensitivity, we have shown that its associated oxidative stress can have radioprotective effects, including stabilization of the transcription factor hypoxia inducible factor 1 (HIF-1). HIF-1 is known to regulate many of the glycolytic enzymes, thereby promoting aerobic glycolysis, which is known to promote treatment resistance. Thus, we hypothesized that reoxygenation after radiation would increase glycolysis. We previously showed that blockade of oxidative stress using a superoxide dismutase (SOD) mimic during reoxygenation can downregulate HIF-1 activity. Here we tested whether concurrent use of this drug with radiotherapy would reduce the switch to a glycolytic phenotype. Materials and methods: 40 mice with skin fold window chambers implanted with 4T1 mammary carcinomas were randomized into (1) no treatment, (2) radiation alone, (3) SOD mimic alone, and (4) SOD mimic with concurrent radiation. All mice were imaged on the ninth day following tumor implantation (30 h following radiation treatment) following injection of a fluorescent glucose analog, 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG). Hemoglobin saturation was measured by using hyperspectral imaging to quantify oxygenation state. Results: Mice treated with radiation showed significantly higher 2-NBDG fluorescence compared to controls (p = 0.007). Hemoglobin saturation analysis demonstrated reoxygenation following radiation, coinciding with the observed increase in glycolysis. The concurrent use of the SOD mimic with radiation demonstrated a significant reduction in 2-NBDG fluorescence compared to effects seen after radiation alone, while having no effect on reoxygenation. Conclusions: Radiation induces an increase in tumor glucose demand approximately 30 h following therapy during reoxygenation. The use of an SOD mimic can prevent the increase in aerobic glycolysis when used

  9. Radiation-induced mucositis pain in laryngeal cancer

    International Nuclear Information System (INIS)

    Takahashi, Atsuhito; Shoji, Kazuhiko; Iki, Takehiro; Mizuta, Masanobu; Matsubara, Mami

    2009-01-01

    Radiation therapy in those with head and neck malignancies often triggers painful mucositis poorly controlled by nonsteroidal antiinflammatory drugs (NSAIDs). To better understand how radiation-induced pain develops over time, we studied the numerical rating scale (NRS 0-5) pain scores from 32 persons undergoing radiation therapy of 60-72 Gy for newly diagnosed laryngeal cancer. The degree of mucositis was evaluated using Common Terminology Criteria for Adverse Events version3.0 (CTCAE v3.0). We divided the 32 into a conventional fractionation (CF) group of 14 and a hyperfractionation (HF) group of 18, and further divided laryngeal cancer into a small-field group of 23 and a large-field group of 9. The mucositis pain course was similar in CF and HF, but mucositis pain was severer in the HF group, which also required more NSAIDs. Those in the large-field group had severer pain and mucositis and required more NSAIDs than those in the small-field group. We therefore concluded that small/large-field radiation therapy, rather fractionation type, was related to the incidence of radiation-induced mucositis pain. (author)

  10. Radiation-induced soft-tissue and bone sarcoma

    International Nuclear Information System (INIS)

    Kim, J.H.; Chu, F.C.; Woodard, H.Q.; Melamed, R.; Huvos, A.; Cantin, J.

    1978-01-01

    From the records of Memorial Hospital of the past 50 years, 47 cases with an established diagnosis of radiation-induced sarcoma were identified and divided into two groups: the first included 20 cases of soft-tissue sarcoma arising from irradiated tissues, and the second comprised 27 cases of bone sarcoma arising from normal bones in the irradiated field. Medians for the latent periods from irradiation to diagnosis of bone and soft-tissue sarcoma were 11 and 12, years, respectively. In bone sarcomas, the latent period was longer after larger radiation doses and children appeared to be more susceptible to cancer induction than adults. Criteria for establishing the diagnosis of radiation-induced sarcoma and the magnitude of the risk of bone sarcoma are discussed

  11. Radiation-induced ηe-modes

    International Nuclear Information System (INIS)

    Shukla, P.K.; Yu, M.Y.

    1990-01-01

    Impurity radiation in a plasma can cause not only static instabilities, but also dynamic instabilities related to the drift and acoustic waves. Radiative instabilities are of much interest because they are associated with relatively high frequency and short wavelength fluctuations, which have been suspected to be responsible for anomalous electron energy transport in tokamak edge plasmas. In this paper, we consider radiation-induced η e instabilities, taking into account electrostatic effects as well as density and temperature inhomogeneities. Also included are the effects of finite gyroradius and dissipation. It is found that the latter can cause strong linear coupling between the modes of interest. The resulting instabilities can have larger growth rates than the static radiative instability. Analytical expressions for the growth rates and instability regimes are given for the limiting cases of practical interest. In particular, it is shown that the η e -mode can couple to both radiation and dissipation to cause resistive instabilities. The parameter regimes of the original radiative as well as the dissipative modes are thereby broadened and shifted because of the interaction. (author) 3 refs

  12. Radiation induced diffusion as a method to protect surface

    International Nuclear Information System (INIS)

    Baumvol, I.J.R.

    1980-01-01

    Radiation induced diffusion forms a coating adeherent and without interface on the surface of metalic substrates. This coating improves the behaviour of metal to corrosion and abrasion. The effect of radiation induced diffusion of tin and calcium on pure iron surface is described and analyzed in this work. (author) [pt

  13. Radiation-induced cancer

    International Nuclear Information System (INIS)

    Dutrillaux, B.; CEA Fontenay-aux-Roses, 92

    1998-01-01

    The induction of malignant diseases is one of the most concerning late effects of ionising radiation. A large amount of information has been collected form atomic bomb survivors, patients after therapeutic irradiation, occupational follow-up and accidentally exposed populations. Major uncertainties persist in the (very) low range i.e, population and workers radioprotection. A review of the biological mechanisms leading to cancer strongly suggests that the vast majority of radiation-induced malignancies arise as a consequence of recessive mutations can be unveiled by ageing, this process being possibly furthered by constitutional or acquired genomic instability. The individual risk is likely to be very low, probably because of the usual dose level. However, the magnitude of medical exposure and the reliance of our societies on nuclear industry are so high that irreproachable decision-making processes and standards for practice are inescapable. (author)

  14. Methylglyoxal-bis(guanylhydrazone), a polyamine analogue, sensitized γ-radiation-induced cell death in HL-60 leukemia cells Sensitizing effect of MGBG on γ-radiation-induced cell death.

    Science.gov (United States)

    Kim, Jin Sik; Lee, Jin; Chung, Hai Won; Choi, Han; Paik, Sang Gi; Kim, In Gyu

    2006-09-01

    Methylglyoxal-bis(guanylhydrazone) (MGBG), a polyamine analogue, has been known to inhibit the biosynthesis of polyamines, which are important in cell proliferation. We showed that MGBG treatment significantly affected γ-radiation-induced cell cycle transition (G(1)/G(0)→S→G(2)/M) and thus γ-radiation-induced cell death. As determined by micronuclei and comet assay, we showed that it sensitized the cytotoxic effect induced by γ-radiation. One of the reasons is that polyamine depletion by MGBG treatment did not effectively protect against the chemical (OH) or physical damage to DNA caused by γ-radiation. Through in vitro experiment, we confirmed that DNA strand breaks induced by γ-radiation was prevented more effectively in the presence of polyamines (spermine and spermidine) than in the absence of polyamines. MGBG also blocks the cell cycle transition caused by γ-radiation (G(2) arrest), which helps protect cells by allowing time for DNA repair before entry into mitosis or apoptosis, via the down regulation of cyclin D1, which mediates the transition from G(1) to S phase of cell cycle, and ataxia telangiectasia mutated, which is involved in the DNA sensing, repair and cell cycle check point. Therefore, the abrogation of G(2) arrest sensitizes cells to the effect of γ-radiation. As a result, γ-radiation-induced cell death increased by about 2.5-3.0-fold in cells treated with MGBG. However, exogenous spermidine supplement partially relieved this γ-radiation-induced cytotoxicity and cell death. These findings suggest a potentially therapeutic strategy for increasing the cytotoxic efficacy of γ-radiation.

  15. Evidence for Radiation-Induced Disseminated Intravascular Coagulation as a Major Cause of Radiation-Induced Death in Ferrets

    Energy Technology Data Exchange (ETDEWEB)

    Krigsfeld, Gabriel S.; Savage, Alexandria R.; Billings, Paul C.; Lin, Liyong; Kennedy, Ann R., E-mail: akennedy@mail.med.upenn.edu

    2014-03-15

    Purpose: The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Methods and Materials: Ferrets were exposed to 0 to 2 Gy of whole-body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. Results: The lethal dose of radiation to 50% of the population (LD{sub 50}) of the ferrets was established at ∼1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Conclusions: Data presented here provide evidence that death at the LD{sub 50} in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals.

  16. A case of radiation-induced osteosarcoma of the maxilla

    International Nuclear Information System (INIS)

    Tanaka, Rie; Asato, Ryo; Tanaka, Shinzo; Hiratsuka, Yasuyuki; Ito, Juichi

    2003-01-01

    Radiation-induced osteosarcoma in the head and neck region is very rare. A 68-year-old female, who had been treated with radiation for malignant lymphoma of the right maxillary sinus, presented with right cheek swelling. Imaging examinations demonstrated a huge mass occupying the right nasal cavity and paranasal sinuses. Total maxillectomy was performed, and the tumor was histologically diagnosed as osteosarcoma. Diagnosis and treatment for radiation-induced osteosarcoma in the head and neck is discussed. (author)

  17. A case of radiation-induced osteosarcoma of the maxilla

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Rie [Shimada City Hospital, Shizuoka (Japan); Asato, Ryo; Tanaka, Shinzo; Hiratsuka, Yasuyuki; Ito, Juichi [Kyoto Univ. (Japan). Faculty of Medicine

    2003-02-01

    Radiation-induced osteosarcoma in the head and neck region is very rare. A 68-year-old female, who had been treated with radiation for malignant lymphoma of the right maxillary sinus, presented with right cheek swelling. Imaging examinations demonstrated a huge mass occupying the right nasal cavity and paranasal sinuses. Total maxillectomy was performed, and the tumor was histologically diagnosed as osteosarcoma. Diagnosis and treatment for radiation-induced osteosarcoma in the head and neck is discussed. (author)

  18. [The occupational radiation-induced cataract in five industrial radiographers].

    Science.gov (United States)

    Benzarti Mezni, A; Loukil, I; Hriz, N; Kallel, K; Mlaiki, N; Ben Jemaâ, A

    2012-04-01

    The industrial uses of ionizing radiation in Tunisia are expanding, especially in industry and most particularly in the nondestructive testing of welds. Thus workers operating in the non-destructive testing of welds may develop a radiation-induced cataract varying in time to onset depending on the dose. To describe the characteristics of the radiation-induced cataract in patients exposed to ionizing radiation, determine the risk factors of radiation-induced cataracts. This was an anamnestic, clinical, and environmental study of five cases of radiation-induced cataract in workers employed in non-destructive testing of welds. This series of five cases had a mean age of 30.2 years and 5.53 years of work experience, ranging from 14 months to 15 years. All the patients were male and industrial radiographers specialized in nondestructive testing of welds. The average duration of exposure to ionizing radiation was 5.53 years. None of the patients had worn protective gear such as eye goggles. The ophthalmic check-up for the five special industrial radiographers showed punctuate opacities in three cases, punctiform opacities in one eye in one case, and phacosclerosis with bilateral lens multiple crystalline stromal opacities in a case of micro-lens opacities in both eyes with opalescence of both eyes in one case. These cataracts had been declared as occupational diseases. The value of a specialized ophthalmologic surveillance among these workers and the early diagnosis of lens opacities must be emphasized. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  19. Radiation-induced recurrent intestinal pseudo-obstruction

    International Nuclear Information System (INIS)

    Conklin, J.L.; Anuras, S.

    1981-01-01

    The syndrome of intestinal pseudo-obstruction is a complex of signs and symptoms of intestinal obstruction without evidence of mechanical obstruction of the intestinal lumen. A patient with radiation-induced intestinal pseudoobstruction is described. The patient is a 74-year old woman with a history of chronic diarrhea, recurrent episodes of crampy abdominal pain, nausea and vomiting since receiving a 13,000 rad radiation dose to the pelvis in 1954. She has been hospitalized on many occasions for symptoms and signs of bowel obstruction. Upper gastrointestinal contrast roentgenograms with small bowel follow-through done during these episodes revealed multiple dilated loops of small bowel with no obstructing lesion. Barium enemas revealed no obstructing lesion. Each episode resolved with conservative therapy. Other secondary causes for intestinal pseudo-obstruction were ruled out in our patient. She gave no history of familial gastrointestinal disorders. Although postirradiation motility abnormalities have been demonstrated experimentally this is the first report of radiation induced intestinal pseudo-obstruction

  20. Radiation-induced caries as the late effect of radiation therapy in the head and neck region

    Directory of Open Access Journals (Sweden)

    Katarzyna Dobroś

    2015-10-01

    Full Text Available Overall improvement in the nationwide system of medical services has consequently boosted the number of successfully treated patients who suffer from head and neck cancer. It is essential to effectively prevent development of radiation-induced caries as the late effect of radiation therapy. Incidence and severity of radiation-induced changes within the teeth individually vary depending on the patient’s age, actual radiation dose, size of radiation exposure field, patient’s general condition and additional risk factors. Inadequately managed treatment of caries may lead to loss of teeth, as well as prove instrumental in tangibly diminishing individual quality of life in patients. Furthermore, the need to have the teeth deemed unyielding or unsuitable for the application of conservative methods of treatment duly extracted is fraught for a patient with an extra hazard of developing osteoradionecrosis (ORN, while also increasing all attendant therapeutic expenditures. The present paper aims to offer some practical insights into currently available methods of preventing likely development of radiation-induced caries.

  1. Diseases induced by ionising radiation

    International Nuclear Information System (INIS)

    1984-11-01

    An interim report is presented by the Industrial Injuries Advisory Council in accordance with Section 141 of the Social Security Act 1975 on the question whether the terms of prescription for occupational diseases induced by ionising radiation should be amended to cover a wider range of conditions. A lack of persuasive statistical data has prevented reliable estimates of health risks of radiation workers in the UK to be made. However the report gives details of the progress made so far and the difficulties encountered. (U.K.)

  2. Radiation-induced cancers of the head and neck, (3)

    International Nuclear Information System (INIS)

    Umatani, Katsunori; Satoh, Takeo; Yoshino, Kunitoshi; Takagi, Tadashi; Fujii, Takashi; Hatta, Chihiro; Maetani, Chikahide; Lu, Bo

    1989-01-01

    This paper discusses twenty patients with radiation-induced cancers of the head and neck treated in the Department of Otorhinolaryngology, the Center for Adult Diseases, Osaka, from January 1979 to December 1985. The most common site of radiation-induced cancers was the hypopharynx and cervical esophagus (70%). We found synchronous double cancers in 2 out of the 20 patients (10%). One patient had hypopharyngeal cancer and thyroid cancer, and the other had oropharyngeal cancer and thyroid cancer. All of the laryngeal cancers were in the supraglottic area. Cancer of the hypopharynx and cervical esophagus occurred more frequently in females (1:3.7 males-females ratio). Half of the patients (10/20) had received irradiation for tuberculous cervical adenitis and 8 patients had been irradiated for malignant tumors. The averaged latent period in the patients who had irradiated for benign conditions was 37.4 years, and that for malignant diseases was 16.0 years. Therefore the latent period of the former was 2.3 times as long as that of the latter. The incidence of radiation-induced cancers in all the patients who had the cancer of the hypopharynx and cervical esophagus was 9% and that of the laryngeal cancer was 0.7%. The incidence of radiation-induced cancers in the hypopharynx and cervical esophagus remarkably differed from that in the larynx. However, it was suggested that the larynx was as resistant to radiation induction as the hypopharynx. Six of the 20 patients (30%) had radiation-induced thyroid tumors. Among them, the incidence of cancers was 33%. (author)

  3. γ-radiation induced tetracycline removal in an aqueous solution

    International Nuclear Information System (INIS)

    Zhou Fei; Guo Zhaobing; Zhang Chaozhi; Lin Mingyue; Wu Menglong; Zhao Yongfu

    2012-01-01

    Degradation effect of tetracycline (TC) by γ-radiation was investigated in an aqueous solution. The effects of initial concentrations of TC, pH values, combining with H 2 O 2 or CH 3 OH on degradation of TC were studied. Results showed that TC can be effectively degradated by γ-irradiation in an aqueous solution. Degradation of TC could be remarkably improved both in acid solution and alkaline solution, especially when pH value was 9.0. In addition, H 2 O 2 could gently promote degradation of TC induced by γ-radiation. While, CH 3 OH markedly restrained degradation of TC induced by γ-radiation. The degradation mechanism of TC was supposed by results of quantum chemical calculations and LC-MS. Results proved that degradation of TC induced by γ-radiation was mainly ascribed to · OH oxidation. (authors)

  4. Hypofractionated radiation induces a decrease in cell proliferation but no histological damage to organotypic multicellular spheroids of human glioblastomas

    NARCIS (Netherlands)

    Kaaijk, P.; Troost, D.; Sminia, P.; Hulshof, M. C.; van der Kracht, A. H.; Leenstra, S.; Bosch, D. A.

    1997-01-01

    The aim of this study was to examine the effect of radiation on glioblastoma, using an organotypic multicellular spheroid (OMS) model. Most glioblastoma cell lines are, in contrast to glioblastomas in vivo, relatively radiosensitive. This limits the value of using cell lines for studying the

  5. Short-Course Hypofractionated Radiation Therapy With Boost in Women With Stages 0 to IIIa Breast Cancer: A Phase 2 Trial

    International Nuclear Information System (INIS)

    Ahlawat, Stuti; Haffty, Bruce G.; Goyal, Sharad; Kearney, Thomas; Kirstein, Laurie; Chen, Chunxia; Moore, Dirk F.; Khan, Atif J.

    2016-01-01

    Purpose: Conventionally fractionated whole-breast irradiation (WBI) with a boost takes approximately 6 to 7 weeks. We evaluated a short course of hypofractionated (HF), accelerated WBI in which therapy was completed in 3 weeks inclusive of a sequential boost. Methods and Materials: We delivered a whole-breast dose of 36.63 Gy in 11 fractions of 3.33 Gy over 11 days, followed by a lumpectomy bed boost in 4 fractions of 3.33 Gy delivered once daily for a total of 15 treatment days. Acute toxicities were scored using Common Terminology Criteria for Adverse Events version 4. Late toxicities were scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Cosmesis was scored using the Harvard Cosmesis Scale. Our primary endpoint was freedom from locoregional failure; we incorporated early stopping criteria based on predefined toxicity thresholds. Cosmesis was examined as a secondary endpoint. Results: We enrolled 83 women with stages 0 to IIIa breast cancer. After a median follow-up of 40 months, 2 cases of isolated ipsilateral breast tumor recurrence occurred (2 of 83; crude rate, 2.4%). Three-year estimated local recurrence-free survival was 95.9% (95% confidence interval [CI]: 87.8%-98.7%). The 3-year estimated distant recurrence-free survival was 97.3% (95% CI: 89.8%-99.3%). Three-year secondary malignancy-free survival was 94.3% (95% CI: 85.3%-97.8%). Twenty-nine patients (34%) had grade 2 acute toxicity, and 1 patient had a late grade 2 toxicity (fibrosis). One patient had acute grade 3 dermatitis, whereas 2 patients experienced grade 3 late skin toxicity. Ninety-four percent of evaluable patients had good or excellent cosmesis. Conclusions: Our phase 2 institutional study offers one of the shortest courses of HF therapy, delivered in 15 fractions inclusive of a sequential boost. We demonstrated expected low toxicity and high local control rates with good to excellent cosmetic outcomes. This

  6. Involvement of inducible nitric oxide synthase in radiation-induced vascular endothelial damage

    International Nuclear Information System (INIS)

    Hong, Chang-Won; Lee, Joon-Ho; Kim, Suwan; Noh, Jae Myoung; Kim, Young-Mee; Pyo, Hongryull; Lee, Sunyoung

    2013-01-01

    The use of radiation therapy has been linked to an increased risk of cardiovascular disease. To understand the mechanisms underlying radiation-induced vascular dysfunction, we employed two models. First, we examined the effect of X-ray irradiation on vasodilation in rabbit carotid arteries. Carotid arterial rings were irradiated with 8 or 16 Gy using in vivo and ex vivo methods. We measured the effect of acetylcholine-induced relaxation after phenylephrine-induced contraction on the rings. In irradiated carotid arteries, vasodilation was significantly attenuated by both irradiation methods. The relaxation response was completely blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a potent inhibitor of soluble guanylate cyclase. Residual relaxation persisted after treatment with L-N ω -nitroarginine (L-NA), a non-specific inhibitor of nitric oxide synthase (NOS), but disappeared following the addition of aminoguanidine (AG), a selective inhibitor of inducible NOS (iNOS). The relaxation response was also affected by tetraethylammonium, an inhibitor of endothelium-derived hyperpolarizing factor activity. In the second model, we investigated the biochemical events of nitrosative stress in human umbilical-vein endothelial cells (HUVECs). We measured iNOS and nitrotyrosine expression in HUVECs exposed to a dose of 4 Gy. The expression of iNOS and nitrotyrosine was greater in irradiated HUVECs than in untreated controls. Pretreatment with AG, L-N 6 -(1-iminoethyl) lysine hydrochloride (a selective inhibitor of iNOS), and L-NA attenuated nitrosative stress. While a selective target of radiation-induced vascular endothelial damage was not definitely determined, these results suggest that NO generated from iNOS could contribute to vasorelaxation. These studies highlight a potential role of iNOS inhibitors in ameliorating radiation-induced vascular endothelial damage. (author)

  7. Increased radiosensitivity and radiation-induced apoptosis in SRC-3 knockout mice

    International Nuclear Information System (INIS)

    Jin Jie; Wang Yu; Xu Yang; Chen Shilei; Wang Junping; Ran Xinze; Su Yongping; Wang Jin

    2014-01-01

    Steroid receptor coactivator-3 (SRC-3), a multifunctional transcriptional coactivator, plays an important role in regulation of cell apoptosis in chemoresistant cancer cells. However, its role in radiation-induced apoptosis in hematopoietic cells is still unclear. In this study, we used SRC-3 knockout (SRC-3 -/- ) mice to assess the role of SRC-3 in radiation-induced hematopoietic injury in vivo. After a range of doses of irradiation, SRC-3 -/- mice exhibited lower counts of peripheral blood cells and bone marrow (BM) mononuclear cells and excessive BM depression, which resulted in a significantly higher mortality compared with wildtype mice. Moreover, BM mononuclear cells obtained from SRC-3 -/- mice showed a remarkable increase in radiation-induced apoptosis. Collectively, our data demonstrate that SRC-3 plays a role in radiation-induced apoptosis of BM hematopoietic cells. Regulation of SRC-3 might influence the radiosensitivity of hematopoietic cells, which highlights a potential therapeutic target for radiation-induced hematopoietic injury. (author)

  8. Radiation induced changes in the airway - anaesthetic implications

    African Journals Online (AJOL)

    Adele

    CASE REPORT. Southern African Journal of Anaesthesia & Analgesia - May 2004. 19. Radiation ... Summary: Radiation induces a variety of changes in the airway that can potentially lead to difficult intubation. ... Mask holding and ventilation is.

  9. Technique of Injection of Hyaluronic Acid as a Prostatic Spacer and Fiducials Before Hypofractionated External Beam Radiotherapy for Prostate Cancer.

    Science.gov (United States)

    Boissier, Romain; Udrescu, Corina; Rebillard, Xavier; Terrier, Jean-Etienne; Faix, Antoine; Chapet, Olivier; Azria, David; Devonec, Marian; Paparel, Philippe; Ruffion, Alain

    2017-01-01

    To describe a technique combining the implantation of fiducials and a prostatic spacer (hyaluronic acid [HA]) to decrease the rectal toxicity after an image-guided external beam radiotherapy (EBRT) with hypofractionation for prostate cancer and to assess the tolerance and the learning curve of the procedure. Thirty patients with prostate cancer at low or intermediate risk were included in a phase II trial: image-guided EBRT of 62 Gy in 20 fractions of 3.1 Gy with intensity-modulated radiotherapy. A transrectal implantation of 3 fiducials and transperineal injection of 10 cc of HA (NASHA gel spacer, Q-Med AB, Uppsala, Sweden) between the rectum and the prostate was performed by 1 operator. The thickness of HA was measured at 10 points on magnetic resonance imaging to establish a quality score of the injection (maximum score = 10) and determine the learning curve of the procedure. The quality score increased from patients 1-10, 11-20, to 21-30 with respective median scores: 7 [2-10], 5 [4-7], and 8 [3-10]. The average thicknesses of HA between the base, middle part, and apex of the prostate and the rectum were the following: 15.1 mm [6.4-29], 9.8 mm [5-21.2], and 9.9 mm [3.2-21.5]. The injection of the HA induced a median pain score of 4 [1-8] and no residual pain at mid-long term. Creating an interface between the rectum and the prostate and the implantation of fiducials were feasible under local anesthesia with a short learning curve and could become a standard procedure before a hypofractionated EBRT for prostate cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Studies on protective effects of superoxide dismutase on radiation induced-chromosomal aberrations

    International Nuclear Information System (INIS)

    Zheng Siying; Jiang Jiagui; Lin Xingcheng

    1987-09-01

    This study demonstrates that radiation induced-chromosomal aberrations are not only due to the direct effect of radiation h it , but the indirect effect of free radical as well. Therefore, chromosome damage induced by radiation may be reduced by adding exogenous SOD into the radiation exposed lymphocyte culture to eliminate the superoxide free radical which damages DNA. On the other hand, however, the radiosensitivity of lymphocytes can be raised by adding SOD inhibitor (DDC) into the lymphocyte culture, which makes radiation induced-chromosomal damages more severely

  11. Toxic clinical hypoxic radiation sensitizers plus radiation-induced toxicity

    International Nuclear Information System (INIS)

    Richmond, R.C.

    1984-01-01

    The operational definition espoused twelve years ago that clinical hypoxic radiation sensitizers should be nontoxic interferes with the recognition and research of useful radiation sensitizers. Eight years ago the toxic antitumor drug cis-dichlorodiammineplatinum(II) was reported to be a hypoxic radiation sensitizer and the selective antitumor action of this drug was stressed as potentially creating tumor-targeted radiation sensitization. This rationale of oxidative antitumor drugs as toxic and targeted clinical sensitizers is useful, and has led to the study reported here. The antitumor drug cis-(1,1-cyclobutane-dicarboxylato)diammineplatinum(II), or JM-8, is being tested in clinical trials. Cells of S. typhimurium in PBS in the presence of 0.2mM JM-8 are found to be sensitized to irradiation under hypoxic, but not oxic, conditions. JM-8 is nontoxic to bacteria at this concentration, but upon irradiation the JM-8 solution becomes highly toxic. This radiation induced toxicity of JM-8 preferentially develops from hypoxic solution, and thus contributes to the rationale of hypoxic tumor cell destruction

  12. Radiation induced genomic instability

    International Nuclear Information System (INIS)

    Morgan, W.

    2003-01-01

    This presentation will focus on delayed genetic effects occurring in the progeny of cells after exposure to ionizing radiation. We have developed a model system for investigating those genetic effects occurring multiple generations after radiation exposure. The presentation will describe some of the delayed effects observed after radiation exposures including delayed chromosomal rearrangements, and recombination events as determined by a plasmid based assay system. We will present new data on how changes in gene expression as measured by differential display and DNA microarray analysis provides a mechanism by which cells display a memory of irradiation, and introduce candidate genes that may play a role in initiating and perpetuation the unstable phenotype. These results will be discussed in terms of the recently described non-targeted Death Inducing Effect (DIE) where by secreted factors from clones of unstable cells can elicit effects in non irradiated cells and may serve to perpetuate the unstable phenotype in cells that themselves were not irradiated

  13. Carcinogenesis induced by low-dose radiation

    Directory of Open Access Journals (Sweden)

    Piotrowski Igor

    2017-11-01

    Full Text Available Although the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure.

  14. Radiation-induced physical ageing in network arsenic-sulfide/selenide glasses

    International Nuclear Information System (INIS)

    Shpotyuk, M; Golovchak, R; Kozdras, A; Shpotyuk, O

    2010-01-01

    Effect of radiation-induced physical ageing is investigated by differential scanning calorimetry method in As x Se 100-x (10 ≤ x ≤ 42) and As x S 100-x (30 ≤ x ≤ 42) glasses. Obtained results are compared with conventional physical ageing at normal conditions. Significant radiation-induced physical ageing is recorded for glassy As x S 100-x within 30 ≤ x x Se 100-x glasses from the same compositional interval do not show any measurable changes in DSC curves after γ-irradiation. Observed difference in radiation-induced physical ageing in arsenic-sulfide/selenide glasses is explained by a greater lifetime of γ-induced excitations within sulfur-based network in comparison with selenium-based one.

  15. Suppression of radiation-induced in vitro carcinogenesis by ascorbic acid

    International Nuclear Information System (INIS)

    Tauchi, Hiroshi; Sawada, Shozo

    1993-01-01

    The effects of ascorbic acid on radiation-induced in vitro carcinogenesis have been reported using neoplastic transformation system of C3H 10T1/2 cells. In these reports, no suppressive effect on X-ray-induced transformation was observed with 6 weeks' administration of ascorbic acid (daily addition for 5 days per week) by Kennedy (1984), whereas apparent suppression was observed with daily addition for 7 days by Yasukawa et al (1989). We have tested the effects of ascorbic acid on 60 Co gamma-ray or 252 Cf fission neutron-induced transformation in Balb/c 3T3 cells. The transformation induced by both types of radiations was markedly suppressed when ascorbic acid was daily added to the medium during first 8 days of the post-irradiation period. If ascorbic acid was added for a total of 8 days but with a day's interruption in the middle, the suppression of transformation was decreased. These results suggest that continuous presence of ascorbic acid for a certain number of days is needed to suppress radiation-induced transformation. Since ascorbic acid also suppressed the promotion of radiation-induced transformation by TPA when both chemicals were added together into the medium, ascorbic acid might act on the promotion stage of transformation. Therefore, the effect of ascorbic acid on the distribution of protein kinase C activity was also investigated, and possible mechanisms of suppression of radiation-induced transformation by ascorbic acid will be discussed. (author)

  16. Radiation-induced segregation and phase stability in ferritic-martensitic alloy T 91

    Energy Technology Data Exchange (ETDEWEB)

    Wharry, Janelle P.; Jiao Zhijie; Shankar, Vani [University of Michigan, 2355 Bonisteel Blvd, Ann Arbor, MI 48109-2104 (United States); Busby, Jeremy T. [Oak Ridge National Laboratory, 1 Bethel Valley Rd, Oak Ridge, TN 37831 (United States); Was, Gary S., E-mail: gsw@umich.edu [University of Michigan, 2355 Bonisteel Blvd, Ann Arbor, MI 48109-2104 (United States)

    2011-10-01

    Radiation-induced segregation in ferritic-martensitic alloy T 91 was studied to understand the behavior of solutes as a function of dose and temperature. Irradiations were conducted using 2 MeV protons to doses of 1, 3, 7 and 10 dpa at 400 deg. C. Radiation-induced segregation at prior austenite grain boundaries was measured, and various features of the irradiated microstructure were characterized, including grain boundary carbide coverage, the dislocation microstructure, radiation-induced precipitation and irradiation hardening. Results showed that Cr, Ni and Si segregate to prior austenite grain boundaries at low dose, but segregation ceases and redistribution occurs above 3 dpa. Grain boundary carbide coverage mirrors radiation-induced segregation. Irradiation induces formation of Ni-Si-Mn and Cu-rich precipitates that account for the majority of irradiation hardening. Radiation-induced segregation behavior is likely linked to the evolution of the precipitate and dislocation microstructures.

  17. The effects of cysteamine on the radiation-induced apoptosis

    International Nuclear Information System (INIS)

    Choi, Young Min; Cho, Heung Lae; Park, Chang Gyo; Lee, Hyung Sik; Hur, Won Joo

    2000-01-01

    To investigate the pathways of radiation induced apoptosis and the effect of cysteamine (β-mercaptoethylamine), as a radioprotector, on it. HL-60 cells were assigned to control, irradiated, and cysteamine (1 mM, 10 mM) pretreated groups. Irradiation was given in a single fraction of 10 Gy (6 MV x-ray) and cysteamine was administered 1 hour before irradiation. The activities of caspase-8 were measured in control and irradiated group to evaiuate its relation to the radiation induced apoptosis. To evaluate the role of cysteamine in radiation induced apoptosis, the number of viable cells, the expression and activity or caspase-3, and the expression of poly (ADP-ribose) polymerase (PARP) were measured and compared after irradiating the HL cells with cysteamine pretreatment or not. The intracellular caspase-8 activity, known to be related to the death receptor induced apoptosis, was not affected by irradiation( p>0.05). The number of viable cells began to decrease from 6 hours after irradiation (p>0.05), but the number of viable cells in 1 mM cysteamine pretreated group was not decreased after irradiation and was similar to those in the control group. In caspase-3 analyses, known as apoptosis executioner, its expression was not different but its activity was increased by irradialion(p>0.05). However, this increase of activity was suppressed by the pretreatment of 1 mM cysteamine. The cleavage of PARP, thought to be resulted from caspase-3 activation, occurred, after irradiation, which was attenuated by the pretreatment of 1 mM cysteamine. These results show that radiation induced apoptotic process is somewhat different from death receptor induced one and the pretreatment of 1 mM cysteamine has a tendency to decrease the radiation-induced apoptosis in HL-60 cells

  18. Radiation-induced mutagenicity and lethality in Ames tester strains of Salmonella

    International Nuclear Information System (INIS)

    Isildar, M.; Bakale, G.

    1984-01-01

    Mutation and killing induced by X radiation and 60 Co γ radiation were studied in six different histidine-requiring auxotrophs of Salmonella typhimurium. Strain TA100, which is sensitive to base-pair substitutions, and strains TA2637 and TA98, which are sensitive to frameshifts, carry the pKM101 plasmid and exhibit significantly higher radiation-induced mutations compared to their plasmidless parent strains TA1535, TA1537, and TA1538, respectively. Among the plasmid-containing strains, TA98 and TA2637 are much more sensitive to the mutagenic action of radiation than is TA100 based on a comparison with their respective spontaneous mutation rates; however, no uniformity was observed in the responses of the strains to the lethal action of ionizing radiation. The following conclusions are consistent with these observations: (1) the standard Ames Salmonella assay correctly identifies ionizing radiation as a mutagenic agent; (2) frameshift-sensitive parent strains are more sensitive to the mutagenic effects of ionizing radiation than is the only strain studied that is sensitive to base-pair substitutions; and (3) enhancement of mutagenesis and survival is related to plasmid-mediated repair of DNA damage induced by ionizing radiation and does not involve damage induced by Cerenkov-generated uv radiation which is negligible for our irradiation conditions

  19. Radiation-induced cerebrovascular disease in children

    International Nuclear Information System (INIS)

    Wright, T.L.; Bresnan, M.J.

    1976-01-01

    Radiation-induced internal carotid artery occlusion has not been well recognized previously as a cause of childhood cerebrovascular disease. A child who had received radiation as a neonate for a hemangioma involving the left orbit at the age of 6 years experienced a recurrent right-sided paresis, vascular headaches, and speech difficulties. Angiography showed a hypoplastic left carotid artery with occlusion of both the anterior and middle cerebral arteries. Collateral vessels bypassed the occluded-stenotic segments. Review of the literature showed two additional cases of large vessel occlusion in childhood associated with anastomatic telangiectatic vessel development following early radiation therapy of facial hemangioma

  20. Hypofractionated stereotactic radiotherapy of acoustic neuroma. Volume changes and hearing results after 89-month median follow-up

    Energy Technology Data Exchange (ETDEWEB)

    Kranzinger, Manfred; Fastner, Gerd [Paracelsus Medical University Clinics (PMU), University Clinic of Radiotherapy and Radio-Oncology, Salzburg County Hospital, Salzburg (Austria); Zehentmayr, Franz; Sedlmayer, Felix [Paracelsus Medical University Clinics (PMU), University Clinic of Radiotherapy and Radio-Oncology, Salzburg County Hospital, Salzburg (Austria); Salzburg County Hospital, Paracelsus Medical University Clinics, radART - Institute for Research and Development on Advanced Radiation Technologies, Salzburg (Austria); Oberascher, Gerhard [Paracelsus Medical University Clinics (PMU), University Clinic of Ear, Nose and Throat Diseases, Salzburg County Hospital, Salzburg (Austria); Merz, Florian; Rahim, Hassan [Salzburg County Hospital, Paracelsus Medical University Clinics, Medical Radiation Protection Unit, Salzburg (Austria); Nairz, Olaf [Clinic Bad Trissl, Oberaudorf (Germany)

    2014-09-15

    The goal of this work was to evaluate toxicity and local control following hypofractionated stereotactic radiation treatment with special focus on changes in tumor volume and hearing capacity. In all, 29 patients with unilateral acoustic neuroma were treated between 2001 and 2007 within a prospective radiation protocol (7 x 4 Gy ICRU dose). Median tumor volume was 0.9 ml. Follow-up started at 6 months and was repeated annually with MRI volumetry and audiometry. Hearing preservation was defined as preservation of Class A/B hearing according to the guidelines of the American Academy of Otolaryngology (1995). No patient had any intervention after a median imaging follow-up of 89.5 months, one patient showed radiological progression. Transient increase of tumor volume developed in 17/29 patients, whereas 22/29 patients (75.9 %) presented with a volume reduction at last follow-up. A total of 21 patients were eligible for hearing evaluation. Mean pure tone average (PTA) deteriorated from 39.3 to 65.9 dB and mean speech discrimination score (SDS) dropped from 74.3 to 38.1 %. The 5-year actuarial Class A/B hearing preservation rate was 50.0 ± 14.4 %. Radiation increases only minimally, if at all, the hearing deterioration which emerges by observation alone. Presbyacusis is not responsible for this deterioration. Transient tumor enlargement is common. Today radiation of small- and medium-sized acoustic neuroma can be performed with different highly conformal techniques as fractionated treatment or single low-dose radiosurgery with equal results regarding tumor control, hearing preservation, and side effects. Hypofractionation is more comfortable for the patient than conventional regimens and represents a serious alternative to frameless radiosurgery. (orig.) [German] Ziel der Studie war die Evaluierung der Toxizitaet und der lokalen Tumorkontrolle einer hypofraktionierten stereotaktischen Bestrahlung mit besonderem Augenmerk auf Veraenderungen von Tumorvolumen und

  1. Carcinomatous versus radiation-induced brachial plexus neuropathy in breast cancer

    International Nuclear Information System (INIS)

    Bagley, F.H.; Walsh, J.W.; Cady, B.; Salzman, F.A.; Oberfield, R.A.; Pazianos, A.G.

    1978-01-01

    A retrospective study was performed of 18 women in whom ipsilateral brachial plexus neuropathy developed after treatment for carcinoma of the breast. In the absence of metastatic tumor elsewhere, the only distinguishing feature between carcinomatous neuropathy and radiation-induced neuropathy was the symptom-free interval after mastectomy and radiation therapy. Women with an interval of less than a year have radiation-induced neuropathy. Brachial plexus exploration in difficult diagnostic situations will permit early treatment and avoid debilitating loss of function. Brachial plexus exploration for biopsy is safe and free of complications if performed carefully. Treatment of carcinomatous neuropathy is most likely to succeed if the tumor is hormonally sensitive, but radiotherapy may also be effective. Treatment of radiation-induced neuropathy remains largely ineffective

  2. Radiation-induced apoptosis in different pH environments in vitro

    International Nuclear Information System (INIS)

    Lee, Hyung-Sik; Park, Heon J.; Lyons, John C.; Griffin, Robert J.; Auger, Elizabeth A.; Song, Chang W.

    1997-01-01

    Purpose: The effect of environmental pH on the radiation-induced apoptosis in tumor cells in vitro was investigated. Methods and Materials: Mammary adenocarcinoma cells of A/J mice (SCK cells) were irradiated with γ-rays using a 137 Cs irradiator and incubated in media of different pHs. After incubation at 37 deg. C for 24-120 h the extent of apoptosis was determined using agarose gel electrophoresis, TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining, flow cytometry, and release of 3 H from 3 H-thymidine labeled cells. The clonogenicity of the cells irradiated in different pH medium was determined, and the progression of cells through the cell cycle after irradiation in different pHs was also determined with flow cytometry. Results: Irradiation with 2-12 Gy of γ-rays induced apoptosis in SCK cells in pH 7.5 medium within 48 h as judged from the results of four different assays mentioned. Radiation-induced apoptosis declined as the medium pH was lowered from 7.5 to 6.4. Specifically, the radiation-induced degradation of DNA including the early DNA breaks, as determined with the TUNEL method, progressively declined as the medium pH was lowered so that little DNA fragmentation occurred 48 h after irradiation with 12 Gy in pH 6.6 medium. When the cells were irradiated and incubated for 48 h in pH 6.6 medium and the medium was replaced with pH 7.5 medium, DNA fragmentation promptly occurred. DNA fragmentation also occurred even in pH 6.6 medium when the cells were irradiated and maintained in pH 7.5 medium for 8 h or longer post-irradiation before incubation in pH 6.6 medium. The radiation-induced G 2 arrest in pH 6.6 medium lasted markedly longer than that in pH 7.5 medium. Conclusion: Radiation-induced apoptosis in SCK cells in vitro is reversibly suppressed in an acidic environment. Taking the results of four different assays together, it was concluded that early step(s) in the apoptotic pathway, probably the DNA break or upstream of DNA break, is

  3. Hypo-fractionated radiotherapy of breast cancer: long term results of a set of 80 cases treated in the radiotherapy department of the Oran university hospital

    International Nuclear Information System (INIS)

    Boukerche, A.; Yahia, A.; Madouri, R.; Belmiloud, H.; Dali-Youcef, A.F.

    2011-01-01

    The authors report the assessment of the local and locoregional control and of the acute and late toxicity of adjuvant hypo-fractionated radiotherapy in breast cancer treatment. During 1998, 80 women have been treated by conservative or radical surgery and hypo-fractionated tele-cobalto-therapy (36 Gy in five fractions of 3 Gy a week, and a boost of 15 Gy in five fractions in case of conservative surgery). Results are discussed in terms of local and locoregional recurrence, tolerance, late toxicity, global survival, and tumour classification. The irradiation scheme seems perfectly achievable but a greater number of patients and a longer follow-up are required to better assess the efficiency and aesthetic results. Short communication

  4. Low-dose radiation-induced endothelial cell retraction

    International Nuclear Information System (INIS)

    Kantak, S.S.; Onoda, J.M.; Diglio, C.A.; Harper Hospital, Detroit, MI

    1993-01-01

    The data presented here are representative of a series of studies designed to characterize low-dose radiation effects on pulmonary microvascular endothelium. Data suggest that post-irradiation lung injuries (e.g. oedema) may be induced with only a single fraction of therapeutic radiation, and thus microscopic oedema may initiate prior to the lethal effects of radiation on the microvascular endothelium, and much earlier than would be suggested by the time course for clinically-detectable oedema. (author)

  5. Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer.

    Science.gov (United States)

    King, Suzanne N; Dunlap, Neal E; Tennant, Paul A; Pitts, Teresa

    2016-06-01

    Oncologic treatments, such as curative radiotherapy and chemoradiation, for head and neck cancer can cause long-term swallowing impairments (dysphagia) that negatively impact quality of life. Radiation-induced dysphagia comprised a broad spectrum of structural, mechanical, and neurologic deficits. An understanding of the biomolecular effects of radiation on the time course of wound healing and underlying morphological tissue responses that precede radiation damage will improve options available for dysphagia treatment. The goal of this review is to discuss the pathophysiology of radiation-induced injury and elucidate areas that need further exploration.

  6. RhoA GTPase regulates radiation-induced alterations in endothelial cell adhesion and migration

    International Nuclear Information System (INIS)

    Rousseau, Matthieu; Gaugler, Marie-Hélène; Rodallec, Audrey; Bonnaud, Stéphanie; Paris, François; Corre, Isabelle

    2011-01-01

    Highlights: ► We explore the role of RhoA in endothelial cell response to ionizing radiation. ► RhoA is rapidly activated by single high-dose of radiation. ► Radiation leads to RhoA/ROCK-dependent actin cytoskeleton remodeling. ► Radiation-induced apoptosis does not require the RhoA/ROCK pathway. ► Radiation-induced alteration of endothelial adhesion and migration requires RhoA/ROCK. -- Abstract: Endothelial cells of the microvasculature are major target of ionizing radiation, responsible of the radiation-induced vascular early dysfunctions. Molecular signaling pathways involved in endothelial responses to ionizing radiation, despite being increasingly investigated, still need precise characterization. Small GTPase RhoA and its effector ROCK are crucial signaling molecules involved in many endothelial cellular functions. Recent studies identified implication of RhoA/ROCK in radiation-induced increase in endothelial permeability but other endothelial functions altered by radiation might also require RhoA proteins. Human microvascular endothelial cells HMEC-1, either treated with Y-27632 (inhibitor of ROCK) or invalidated for RhoA by RNA interference were exposed to 15 Gy. We showed a rapid radiation-induced activation of RhoA, leading to a deep reorganisation of actin cytoskeleton with rapid formation of stress fibers. Endothelial early apoptosis induced by ionizing radiation was not affected by Y-27632 pre-treatment or RhoA depletion. Endothelial adhesion to fibronectin and formation of focal adhesions increased in response to radiation in a RhoA/ROCK-dependent manner. Consistent with its pro-adhesive role, ionizing radiation also decreased endothelial cells migration and RhoA was required for this inhibition. These results highlight the role of RhoA GTPase in ionizing radiation-induced deregulation of essential endothelial functions linked to actin cytoskeleton.

  7. Radiation-induced osteosarcoma of the calvaria; Case report

    Energy Technology Data Exchange (ETDEWEB)

    Sugita, Yasuo; Shigemori, Minoru; Miyagi, Jun; Ochiai, Satoshi; Lee, Souichi; Watanabe, Toshinori; Abe, Hitoshi; Morimatsu, Minoru [Kurume Univ., Fukuoka (Japan). School of Medicine

    1992-01-01

    The authors report a case of radiation-induced calvarial osteosarcoma. A 58-year-old female received subtotal removal of the pituitary adenoma and 5000 rads postoperative irradiation. Seven years later, an osteoblastic osteosarcoma occurred in the frontotemporal region. She received total tumor removal and chemotherapy. However, computed tomography subsequently revealed multiple small lesions at the margin of the bone flap. A chest x-ray film demonstrated lung metastasis. Local recurrence and lung metastasis require careful attention in radiation-induced osteosarcoma patients. (author).

  8. Effect of dose on radiation-induced conductivity in polymers

    International Nuclear Information System (INIS)

    Tyutnev, A.P.; Saenko, V.S.; Pozhidaev, E.D.; Ikhsanov, R.Sh.

    2007-01-01

    Numerical simulation of radiation-induced conductivity in polymers upon long-term irradiation on the basis of the generalized Rose-Fowler-Vaisberg model, which allows for both dipolar carrier transport and generation of radiation traps during irradiation, was performed. The unusual properties of radiation-induced conductivity, such as the appearance of a maximum on current transients, the absence of a steady state, and a substantial difference between these curves for the first and subsequent irradiation, are rationalized in terms of the formation of free radicals, the major feature of radiolysis in the chemical aspect. This interpretation does not require the involvement of degradation or crosslinking processes, unlike other interpretations that appear in the literature. With the use of low-density polyethylene as an example, it was shown that radiation-induced conductivity both upon pulse and continuous irradiation can satisfactorily be described with the unified set of parameters of the generalized Rose-Fowler-Vaisberg model [ru

  9. Radiation-induced gene amplification in rodent and human cells

    International Nuclear Information System (INIS)

    Luecke-Huhle, C.; Gloss, B.; Herrlich, P.

    1990-01-01

    Ionizing and UV radiations induce amplification of SV40 DNA sequences integrated in the genome of Chinese hamster cells and increase amplification of the dihydrofolate reductase (DHFR) gene during methotrexate selection in human skin fibroblasts of a patient with ataxia telangiectasia. Various types of external (60-Co-γ-rays, 241-Am-α-particles, UV) or internal radiation (caused by the decay of 125 I incorporated into DNA in form of I-UdR) were applied. By cell fusion experiments it could be shown that SV40 gene amplification is mediated by one or several diffusible trans-acting factors induced or activated in a dose dependent manner by all types of radiation. One of these factors binds to a 10 bp sequence within the minimal origin of replication of SV40. In vivo competition with an excess of a synthetic oligonucleotide comprising this sequence blocks radiation-induced amplification. (author) 25 refs.; 8 figs

  10. Radiation-induced spindle cell sarcoma: A rare case report

    Directory of Open Access Journals (Sweden)

    Khan Mubeen

    2009-01-01

    Full Text Available Ionizing radiation has been known to induce malignant transformation in human beings. Radiation-induced sarcomas are a late sequel of radiation therapy. Most sarcomas have been reported to occur after exposure to a radiation dose of 55 Gray (Gy and above, with a dose ranging from 16 to 112 Gys. Spindle cell sarcomas, arising after radiotherapy given to treat the carcinoma of head and neck region is a very uncommon sequel. This is a rare case report of spindle cell sarcoma of left maxilla, in a 24-year-old male, occurring as a late complication of radiotherapy with Cobalt-60 given for the treatment of retinoblastoma of the left eye 21 years back.

  11. Radiation induced microbial pesticide

    International Nuclear Information System (INIS)

    Kim, Ki Yup; Lee, Young Keun; Kim, Jae Sung; Kim, Jin Kyu; Lee, Sang Jae

    2000-01-01

    To control plant pathogenic fungi, 4 strains of bacteria (K1, K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 13 kinds of fungi. Mutants of K1 and YS1 strains were induced by gamma-ray radiation and showed promising antifungal activities. These wild type and mutants showed resistant against more than 27 kinds of commercial pesticides among 30 kinds of commercial pesticides test particularly, YS1-1006 mutant strain showed resistant against hydrogen oxide. And mutants had increased antifungal activity against Botryoshaeria dothidea. These results suggested that radiation could be an useful method for the induction of functional mutants. (author)

  12. Radiation-induced chondrosarcoma of the maxilla 7-year after combined chemoradiation for tonsillar lymphoma.

    Science.gov (United States)

    Mohammadianpanah, M; Gramizadeh, B; Omidvari, Sh; Mosalaei, A

    2004-01-01

    Radiation-induced sarcoma is a rare complication of radiation therapy. We report a case of radiation-induced chondrosarcoma of the maxilla. An 80-year-old Persian woman developed radiation-induced chondrosarcoma of the left maxilla 7 years after combined chemotherapy and external beam radiation therapy for the Ann Arbor stage IE malignant lymphoma of the right tonsil. She underwent suboptimal tumour resection and died due to extensive locoregional disease 8 months later. An English language literature search of Medline using the terms chondrosarcoma, radiation-induced sarcoma and maxilla revealed only one earlier reported case. We describe the clinical and pathological features of this case and review the literature on radiation-induced sarcomas.

  13. Radiation-induced chondrosarcoma of the maxilla 7-year after combined chemoradiation for tonsillar lymphoma

    Directory of Open Access Journals (Sweden)

    Mohammadianpanah M

    2004-07-01

    Full Text Available Radiation-induced sarcoma is a rare complication of radiation therapy. We report a case of radiation-induced chondrosarcoma of the maxilla. An 80-year-old Persian woman developed radiation-induced chondrosarcoma of the left maxilla 7 years after combined chemotherapy and external beam radiation therapy for the Ann Arbor stage IE malignant lymphoma of the right tonsil. She underwent suboptimal tumour resection and died due to extensive locoregional disease 8 months later. An English language literature search of Medline using the terms chondrosarcoma, radiation-induced sarcoma and maxilla revealed only one earlier reported case. We describe the clinical and pathological features of this case and review the literature on radiation-induced sarcomas.

  14. Radiation-induced physical ageing in network arsenic-sulfide/selenide glasses

    Energy Technology Data Exchange (ETDEWEB)

    Shpotyuk, M; Golovchak, R; Kozdras, A; Shpotyuk, O, E-mail: shpotyuk@novas.lviv.ua

    2010-11-15

    Effect of radiation-induced physical ageing is investigated by differential scanning calorimetry method in As{sub x}Se{sub 100-x} (10 {<=} x {<=} 42) and As{sub x}S{sub 100-x} (30 {<=} x {<=} 42) glasses. Obtained results are compared with conventional physical ageing at normal conditions. Significant radiation-induced physical ageing is recorded for glassy As{sub x}S{sub 100-x} within 30 {<=} x < 40 range, while As{sub x}Se{sub 100-x} glasses from the same compositional interval do not show any measurable changes in DSC curves after {gamma}-irradiation. Observed difference in radiation-induced physical ageing in arsenic-sulfide/selenide glasses is explained by a greater lifetime of {gamma}-induced excitations within sulfur-based network in comparison with selenium-based one.

  15. ROS Mediates Radiation-Induced Differentiation in Human Lung Fibroblast

    International Nuclear Information System (INIS)

    Park, Sa Rah; Ahn, Ji Yeon; Kim, Mi Hyeung; Lim, Min Jin; Yun, Yeon Sook; Song, Jie Young

    2009-01-01

    One of the most common tumors worldwide is lung cancer and the number of patients with lung cancer received radiotherapy is increasing rapidly. Although radiotherapy may have lots of advantages, it can also induce serious adverse effects such as acute radiation pneumonitis and pulmonary fibrosis. Pulmonary fibrosis is characterized by excessive production of smooth muscle actin-alpha (a-SMA) and accumulation of extracellular matrix (ECM) such as collagen and fibronectin. There has been a great amount of research about fibrosis but the exact mechanism causing the reaction is not elucidated especially in radiation-induced fibrosis. Until now it has been known that several factors such as transforming growth factor (TGF-b), tumor necrosis factor (TNF), IL-6, platelet-derived growth factor (PDGF) and reactive oxygen species are related to fibrosis. It is also reported that reactive oxygen species (ROS) can be induced by radiation and can act as a second messenger in various signaling pathways. Therefore we focused on the role of ROS in radiation induced fibrosis. Here, we suggest that irradiation generate ROS mainly through NOX4, result in differentiation of lung fibroblast into myofibroblast

  16. Inhibition of radiation-induced polyuria by histamine receptor antagonists

    Energy Technology Data Exchange (ETDEWEB)

    Donlon, M.A.; Melia, J.A.; Helgeson, E.A.; Wolfe, W.W.

    1986-03-01

    In previous studies the authors have demonstrated that gamma radiation results in polyuria, which is preceded by polydypsia. This suggests that the increased thirst elicited by radiation causes increased urinary volume (UV). Histamine, which is released following radiation exposure, also elicits drinking by nonirradiated rats when administered exogenously. In this study the authors have investigated both the role of water deprivation and the effect of histamine receptor antagonists (HRA) on radiation-induced polyuria. Sprague-Dawley rats were housed individually in metabolic cages. Water was allowed ad libitum except in deprivation experiments where water was removed for 24 hr immediately following radiation. Cimetidine (CIM), an H2 HRA, and dexbromopheniramine (DXB), an H1 HRA, were administered i.p. (16 and 1 mg/kg, respectively) 30 min prior to irradiation (950 rads from a cobalt source). UV was determined at 24-hr intervals for 3 days preceding irradiation and 24 hr postirradiation. UV in DXB treated rats was significantly reduced 24 hr postirradiation (CON = 427 +/- 54%; DXB = 247 +/- 39% of preirradiated CON) compared to postirradiation control values. CIM did not affect postirradiation UV. These data suggest that radiation-induced polyuria is caused by polydypsia which is, in part, mediated by histamine induced by an H1 receptor.

  17. Inhibition of radiation-induced polyuria by histamine receptor antagonists

    International Nuclear Information System (INIS)

    Donlon, M.A.; Melia, J.A.; Helgeson, E.A.; Wolfe, W.W.

    1986-01-01

    In previous studies the authors have demonstrated that gamma radiation results in polyuria, which is preceded by polydypsia. This suggests that the increased thirst elicited by radiation causes increased urinary volume (UV). Histamine, which is released following radiation exposure, also elicits drinking by nonirradiated rats when administered exogenously. In this study the authors have investigated both the role of water deprivation and the effect of histamine receptor antagonists (HRA) on radiation-induced polyuria. Sprague-Dawley rats were housed individually in metabolic cages. Water was allowed ad libitum except in deprivation experiments where water was removed for 24 hr immediately following radiation. Cimetidine (CIM), an H2 HRA, and dexbromopheniramine (DXB), an H1 HRA, were administered i.p. (16 and 1 mg/kg, respectively) 30 min prior to irradiation (950 rads from a cobalt source). UV was determined at 24-hr intervals for 3 days preceding irradiation and 24 hr postirradiation. UV in DXB treated rats was significantly reduced 24 hr postirradiation (CON = 427 +/- 54%; DXB = 247 +/- 39% of preirradiated CON) compared to postirradiation control values. CIM did not affect postirradiation UV. These data suggest that radiation-induced polyuria is caused by polydypsia which is, in part, mediated by histamine induced by an H1 receptor

  18. Changes of the liver volume and the Child-Pugh score after high dose hypofractionated radiotherapy in patients with small hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kim, Young Il; Park, Hee Chul; Lim, Do Hoon; Park, Hyo Jung; Park, Su Yeon; Kim, Jin Sung; Han, Young Yih; Kang, Sang Won; Paik, Seung Woon

    2012-01-01

    To investigate the safety of high dose hypofractionated radiotherapy (RT) in patients with small hepatocellular carcinoma (HCC) in terms of liver volumetric changes and clinical liver function. We retrospectively reviewed 16 patients with small HCC who were treated with high dose hypofractionated RT between 2006 and 2009. The serial changes of the liver volumetric parameter were analyzed from pre-RT and follow-up (FU) computed tomography (CT) scans. We estimated linear time trends of whole liver volume using a linear mixed model. The serial changes of the Child-Pugh (CP) scores were also analyzed in relation to the volumetric changes. Mean pre-RT volume of entire liver was 1,192.2 mL (range, 502.6 to 1,310.2 mL) and mean clinical target volume was 14.7 mL (range, 1.56 to 70.07 mL). Fourteen (87.5%) patients had 4 FU CT sets and 2 (12.5%) patients had 3 FU CT sets. Mean interval between FU CT acquisition was 2.5 months. After considering age, gender and the irradiated liver volume as a fixed effects, the mixed model analysis confirmed that the change in liver volume is not significant throughout the time course of FU periods. Majority of patients had a CP score change less than 2 except in 1 patient who had CP score change more than 3. The high dose hypofractionated RT for small HCC is relatively safe and feasible in terms of liver volumetric changes and clinical liver function.

  19. Current study on ionizing radiation-induced mitochondial DNA damage and mutations

    International Nuclear Information System (INIS)

    Zhou Xin; Wang Zhenhua; Zhang Hong

    2012-01-01

    Current advance in ionizing radiation-induced mitochondrial DNA damage and mutations is reviewed, in addition with the essential differences between mtDNA and nDNA damage and mutations. To extent the knowledge about radiation induced mitochondrial alterations, the researchers in Institute of Modern Physics, Chinese Academy of Sciences developed some technics such as real-time PCR, long-PCR for accurate quantification of radiation induced damage and mutations, and in-depth investigation about the functional changes of mitochondria based on mtDNA damage and mutations were also carried out. In conclusion, the important role of mitochondrial study in radiation biology is underlined, and further study on mitochondrial study associated with late effect and metabolism changes in radiation biology is pointed out. (authors)

  20. Pathophysiological Responses in Rat and Mouse Models of Radiation-Induced Brain Injury.

    Science.gov (United States)

    Yang, Lianhong; Yang, Jianhua; Li, Guoqian; Li, Yi; Wu, Rong; Cheng, Jinping; Tang, Yamei

    2017-03-01

    The brain is the major dose-limiting organ in patients undergoing radiotherapy for assorted conditions. Radiation-induced brain injury is common and mainly occurs in patients receiving radiotherapy for malignant head and neck tumors, arteriovenous malformations, or lung cancer-derived brain metastases. Nevertheless, the underlying mechanisms of radiation-induced brain injury are largely unknown. Although many treatment strategies are employed for affected individuals, the effects remain suboptimal. Accordingly, animal models are extremely important for elucidating pathogenic radiation-associated mechanisms and for developing more efficacious therapies. So far, models employing various animal species with different radiation dosages and fractions have been introduced to investigate the prevention, mechanisms, early detection, and management of radiation-induced brain injury. However, these models all have limitations, and none are widely accepted. This review summarizes the animal models currently set forth for studies of radiation-induced brain injury, especially rat and mouse, as well as radiation dosages, dose fractionation, and secondary pathophysiological responses.

  1. Cell kinetic studies on radiation induced leukemogenesis

    International Nuclear Information System (INIS)

    Nakao, Isamu; Suzuki, Gen; Imai, Yasufumi; Kawase, Yoshiko; Nose, Masako; Hirashima, Kunitake; Bessho, Masami

    1989-01-01

    The purpose of this study was threefold: (1) to determine the clonal origin of radiation-induced thymic lymphoma in mice with cellular mosaicism for phosphoglycerate kinase; (2) to determine the incidence and latent period of myeloid leukemia and thymic lymphoma induced by whole-body exposure to median doses (3.0 Gy or less) in RFM/MsNrs-2 mice; and (3) to examine the influence of human recombinant interleukin-2 (hrIL-2). Thymic lymphoma was of a single cell origin. The incidence of radiation-induced myeloid leukemia and thymic lymphoma in RFM mice increased in a dose dependent fashion. Mean latent periods of both myeloid leukemia and thymic lymphoma after irradiation became shorter in proportion to radiation doses. When hrIL-2 was injected to RFM mice receiving 3.0 Gy, mean survivals were shorter in thymoma-bearing mice than the control mice. This suggested that hrIL-2 shortens the promotion step of thymoma. Administration of hrIL-2 failed to alter the incidence of myeloid leukemia or the mean survival of mice having myeloid leukemia, indicating that the protocol of hrIL-2 administration was not so sufficient as to alter the myeloid leukemogenesis. (Namekawa, K)

  2. Image Guidance and Assessment of Radiation Induced Gene Therapy

    National Research Council Canada - National Science Library

    Pelizzari, Charles

    2004-01-01

    Image guidance and assessment techniques are being developed for combined radiation/gene therapy, which utilizes a radiation-inducible gene promoter to cause expression of tumor necrosis factor alpha...

  3. The genetics of radiation-induced osteosarcoma

    International Nuclear Information System (INIS)

    Rosemann, M.; Kuosaite, V.; Nathrath, M.; Atkinson, M.J.

    2002-01-01

    Individual genetic variation can influence susceptibility to the carcinogenic effects of many environmental carcinogens. In radiation-exposed populations those individuals with a greater genetically determined susceptibility would be at greater risk of developing cancer. To include this modification of risk into radiation protection schemes it is necessary to identify the genes responsible for determining individual sensitivity. Alpha-particle-induced osteosarcoma in the mouse has been adopted as a model of human radiation carcinogenesis, and genome-wide screens have been conducted for allelic imbalance and genetic linkage. These studies have revealed a series of genes involved in determining the sensitivity to radiogenic osteosarcoma formation. (author)

  4. Radiation induced DNA damage and repair in mutagenesis

    International Nuclear Information System (INIS)

    Strniste, G.F.; Chen, D.J.; Okinaka, R.T.

    1987-01-01

    The central theme in cellular radiobiological research has been the mechanisms of radiation action and the physiological response of cells to this action. Considerable effort has been directed toward the characterization of radiation-induced DNA damage and the correlation of this damage to cellular genetic change that is expressed as mutation or initiating events leading to cellular transformation and ultimately carcinogenesis. In addition, there has been a significant advancement in their understanding of the role of DNA repair in the process of mutation leading to genetic change in cells. There is extensive literature concerning studies that address radiation action in both procaryotic and eucaryotic systems. This brief report will make no attempt to summarize this voluminous data but will focus on recent results from their laboratory of experiments in which they have examined, at both the cellular and molecular levels, the process of ionizing radiation-induced mutagenesis in cultured human cells

  5. Study on DNA damages induced by UV radiation

    International Nuclear Information System (INIS)

    Doan Hong Van; Dinh Ba Tuan; Tran Tuan Anh; Nguyen Thuy Ngan; Ta Bich Thuan; Vo Thi Thuong Lan; Tran Minh Quynh; Nguyen Thi Thom

    2015-01-01

    DNA damages in Escherichia coli (E. coli) exposed to UV radiation have been investigated. After 30 min of exposure to UV radiation of 5 mJ/cm"2, the growth of E. coli in LB broth medium was about only 10% in compared with non-irradiated one. This results suggested that the UV radiation caused the damages for E. coli genome resulted in reduction in its growth and survival, and those lesions can be somewhat recovered. For both solutions of plasmid DNAs and E. coli cells containing plasmid DNA, this dose also caused the breakage on single and double strands of DNA, shifted the morphology of DNA plasmid from supercoiled to circular and linear forms. The formation of pyrimidine dimers upon UV radiation significantly reduced when the DNA was irradiated in the presence of Ganoderma lucidum extract. Thus, studies on UV-induced DNA damage at molecular level are very essential to determine the UV radiation doses corresponding to the DNA damages, especially for creation and selection of useful radiation-induced mutants, as well as elucidation the protective effects of the specific compounds against UV light. (author)

  6. Radiation-induced Pulmonary Damage in Lung Cancer Patients

    International Nuclear Information System (INIS)

    Chung, Su Mi; Choi, Ihl Bohng; Kang, Mi Mun; Kim, In Ah; Shinn, Kyung Sub

    1993-01-01

    Purpose: A retrospective analysis was performed to evaluate the incidence of radiation induced lung damage after the radiation therapy for the patients with carcinoma of the lung. Method and Materials: Sixty-six patients with lung cancer (squamous cell carcinoma 27, adenocarcinoma 14, large cell carcinoma 2, small cell carcinoma 13, unknown 10) were treated with definitive, postoperative or palliative radiation therapy with or without chemotherapy between July 1987 and December 1991. There were 50 males and 16 females with median age of 63 years(range: 33-80 years). Total lung doses ranged from 500 to 6,660 cGy (median 3960 cGy) given in 2 to 38 fractions (median 20) over a range of 2 to 150 days (median 40 days) using 6 MV or 15 MV linear accelerator. To represent different fractionation schedules of equivalent biological effect, the estimated single dose(ED) model, ED=D·N-0.377·T-0.058 was used in which D was the lung dose in cGy, N was the number of fractions, and T was the overall treatment time in days. The range of ED was 370 to 1357. The endpoint was a visible increase in lung density within the irradiated volume on chest X-ray as observed independently by three diagnostic radiologists. Patients were grouped according to ED, treatment duration, treatment modality and age, and the percent incidence of pulmonary damage for each group was determined. Result: In 40 of 66 patients, radiation induced change was seen on chest radiographs between 11 days and 314 days after initiation of radiation therapy. The incidence of radiation pneumonitis was increased according to increased ED, which was statistically significant (p=0.001). Roentgenographic charges consistent with radiation pneumonitis were seen in 100% of patients receiving radiotherapy after lobectomy or pneumonectomy, which was not statistically significant. In 32 patients who also received chemotherapy, there was no difference in the incidence of radiation induced charge between the group with radiation

  7. Characterization of radiation-induced emesis in the ferret

    International Nuclear Information System (INIS)

    King, G.L.

    1988-01-01

    Forty-eight ferrets (Mustela putorius furo) were individually head-shielded and radiated with bilateral 60 Co gamma radiation at 100 cGy min-1 at doses ranging between 49 and 601 cGy. The emetic threshold was observed at 69 cGy, the ED50 was calculated at 77 cGy, and 100% incidence of emesis occurred at 201 cGy. With increasing doses of radiation, the latency to first emesis after radiation decreased dramatically, whereas the duration of the prodromal period increased. Two other sets of experiments suggest that dopaminergic mechanisms play a minor role in radiation-induced emesis in the ferret. Twenty-two animals were injected either intravenously or subcutaneously with 30 to 300 micrograms/kg of apomorphine. Fewer than 50% of the animals vomited to 300 micrograms/kg apomorphine; central dopaminergic receptor activation was apparent at all doses. Another eight animals received 1 mg/kg domperidone prior to either 201 (n = 4) or 401 (n = 4) cGy radiation and their emetic responses were compared with NaCl-injected-irradiated controls (n = 8). At 201 cGy, domperidone significantly reduced only the total time in emetic behavior. At 401 cGy, domperidone had no salutary effect on radiation-induced emesis. The emetic responses of the ferret to radiation and apomorphine are compared with these responses in other vomiting species

  8. Radiation induced estane polymer crosslinking

    International Nuclear Information System (INIS)

    Fletcher, M.; Foster, P.

    1997-01-01

    The exposure of polymeric materials to radiation has been known to induce the effects of crosslinking and degradation. The crosslinking phenomena comes about when two long chain polymers become linked together by a primary bond that extends the chain and increases the viscosity, molecular weight and the elastic modules of the polymer. This process has been observed in relatively short periods of time with fairly high doses of radiation, on the order of several megarads/hour. This paper address low dose exposure over long periods of time to determine what the radiation effects are on the polymeric binder material in PBX 9501. An experimental sample of binder material without explosives will be placed into a thermal and radiation field produced from a W-48 put mod 0. Another sample will be placed in a thermal environment without the radiation. The following is the test plan that was submitted to the Pantex process. The data presented here will be from the first few weeks of exposure and this test will be continued over the next few years. Subsequent data will hopefully be presented in the next compatibility and aging conference

  9. [Induced thymus aging: radiation model and application perspective for low intensive laser radiation].

    Science.gov (United States)

    Sevost'ianova, N N; Trofimov, A V; Lin'kova, N S; Poliakova, V O; Kvetnoĭ, I M

    2010-01-01

    The influence of gamma-radiation on morphofunctional state of thymus is rather like as natural thymus aging. However gamma-radiation model of thymus aging widely used to investigate geroprotectors has many shortcomings and limitations. Gamma-radiation can induce irreversible changes in thymus very often. These changes are more intensive in comparison with changes, which can be observed at natural thymus aging. Low intensive laser radiation can not destroy structure of thymus and its effects are rather like as natural thymus aging in comparison with gamma-radiation effects. There are many parameters of low intensive laser radiation, which can be changed to improve morphofunctional thymus characteristics in aging model. Using low intensive laser radiation in thymus aging model can be very perspective for investigations of aging immune system.

  10. Radioprotective effect of Rapana thomasiana hemocyanin in gamma induced acute radiation syndrome

    International Nuclear Information System (INIS)

    Kindekov, Ivan; Vassilieva, Vladimir; Aljakova, Mitko; Mileva, Milka; Krastev, Dimo; Raynova, Yuliana; Idakieva, Krassimira; Doumanov, Lyuba

    2014-01-01

    The radioprotective effect of Rapana thomasiana hemocyanin (RtH) against radiation-induced injuries (stomach ulcers, survival time and endogenous haemopoiesis) and post-radiation recovery was investigated in male albino mice (C3H strain). Radiation course was in a dose of 7.5 Gy (LD 100/30 - dose that kills 100% of the mice at 30 days) from "1"3"7Cs with a dose of 2.05 Gy/ min. Radiation injuries were manifested by inducing 2 hematopoietic form of acute radiation syndrome. RtH was administered intraperitoneally in a single dose of 50, 100, 150 and 200 mg/kg body weight (b. w.) once a day for five consecutive days before irradiation. The results obtained showed that radiation exposure led to (1) 100% mortality rate, (2) ulceration in the stomach mucosa and (3) decrease formation of spleen colonies as a marker of endogenous haemopoiesis. Administration of RtH at a dose of 200 mg/kg provided better protection against radiation-induced stomach ulceration, mitigated the lethal effects of radiation exposure and recovered endogenous haemopoiesis versus irradiated but not supplemented mice. It could be expected that RtH will find a use in mitigating radiation induced injury and enhanced radiorecovery. Keywords: Rapana thomasiana hemocyanin; acute radiation syndrome; radioprotective effect; spleen colony assay; stomach ulcerations

  11. Modulating factors in the expression of radiation-induced oncogenic transformation

    International Nuclear Information System (INIS)

    Hall, E.J.; Hei, T.K.

    1990-01-01

    Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitaive are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given dose of radiation, and retinoids, selenium, vitamin E, and 5-aminobenzamide that inhibit the expression of transformation. Densely ionizing α-particles, similar to those emitted by radon daughters, are highly effective in inducing transformations and appear to interact in a supra-additive fashion with asbestos fibers. The activation of a known dominant oncogene has not yet been demonstrated in radiation-induced oncogenic transformation. The most likely mechanism for radiation activation of an oncogene would be via the production of a chromosomal translocation. Radiation also efficiently induces deletions and may thus lead to the loss of a suppressor gene

  12. A randomized hypofractionation dose escalation trial for high risk prostate cancer patients: interim analysis of acute toxicity and quality of life in 124 patients

    International Nuclear Information System (INIS)

    Norkus, Darius; Valuckas, Konstantinas Povilas; Karklelyte, Agata; Engels, Benedikt; Versmessen, Harijati; Griskevicius, Romas; De Ridder, Mark; Storme, Guy; Aleknavicius, Eduardas; Janulionis, Ernestas

    2013-01-01

    The α/β ratio for prostate cancer is postulated being in the range of 0.8 to 2.2 Gy, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. To do so, we carried out a randomized trial comparing hypofractionated and conventionally fractionated image-guided intensity modulated radiotherapy (IG-IMRT) in high-risk prostate cancer. Here, we report on acute toxicity and quality of life (QOL) for the first 124 randomized patients. The trial compares 76 Gy in 38 fractions (5 fractions/week) (Arm 1) to 63 Gy in 20 fractions (4 fractions/week) (Arm 2) (IG-IMRT). Prophylactic pelvic lymph node irradiation with 46 Gy in 23 fractions sequentially (Arm 1) and 44 Gy in 20 fractions simultaneously (Arm 2) was applied. All patients had long term androgen deprivation therapy (ADT) started before RT. Both physician-rated acute toxicity and patient-reported QOL using EPIC questionnaire are described. There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity. Compared to conventional fractionation (Arm 1), GI and GU toxicity both developed significantly earlier but also disappeared earlier in the Arm 2, reaching significant differences from Arm 1 at week 8 and 9. In multivariate analyses, only parameter shown to be related to increased acute Grade ≥1 GU toxicity was the study Arm 2 (p = 0.049). There were no statistically significant differences of mean EPIC scores in any domain and sub-scales. The clinically relevant decrease (CRD) in EPIC urinary domain was significantly higher in Arm 2 at month 1 with a faster recovery at month 3 as compared to Arm 1. Hypofractionation at 3.15 Gy per fraction to 63 Gy within 5 weeks was well tolerated. The GI and GU physician-rated acute toxicity both developed earlier but recovered faster using hypofractionation. There was a correlation between acute toxicity and bowel and urinary QOL outcomes. Longer follow-up is needed to determine the significance of these

  13. Expanding the use of real-time electromagnetic tracking in radiation oncology.

    Science.gov (United States)

    Shah, Amish P; Kupelian, Patrick A; Willoughby, Twyla R; Meeks, Sanford L

    2011-11-15

    In the past 10 years, techniques to improve radiotherapy delivery, such as intensity-modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT) for both inter- and intrafraction tumor localization, and hypofractionated delivery techniques such as stereotactic body radiation therapy (SBRT), have evolved tremendously. This review article focuses on only one part of that evolution, electromagnetic tracking in radiation therapy. Electromagnetic tracking is still a growing technology in radiation oncology and, as such, the clinical applications are limited, the expense is high, and the reimbursement is insufficient to cover these costs. At the same time, current experience with electromagnetic tracking applied to various clinical tumor sites indicates that the potential benefits of electromagnetic tracking could be significant for patients receiving radiation therapy. Daily use of these tracking systems is minimally invasive and delivers no additional ionizing radiation to the patient, and these systems can provide explicit tumor motion data. Although there are a number of technical and fiscal issues that need to be addressed, electromagnetic tracking systems are expected to play a continued role in improving the precision of radiation delivery.

  14. Prone Hypofractionated Whole-Breast Radiotherapy Without a Boost to the Tumor Bed: Comparable Toxicity of IMRT Versus a 3D Conformal Technique

    Energy Technology Data Exchange (ETDEWEB)

    Hardee, Matthew E.; Raza, Shahzad; Becker, Stewart J.; Jozsef, Gabor; Lymberis, Stella C. [Department of Radiation Oncology, New York University School of Medicine, New York, NY (United States); Hochman, Tsivia; Goldberg, Judith D. [Division of Biostatistics, New York University School of Medicine, New York, NY (United States); DeWyngaert, Keith J. [Department of Radiation Oncology, New York University School of Medicine, New York, NY (United States); Formenti, Silvia C., E-mail: silvia.formenti@nyumc.org [Department of Radiation Oncology, New York University School of Medicine, New York, NY (United States)

    2012-03-01

    Purpose: We report a comparison of the dosimetry and toxicity of three-dimensional conformal radiotherapy (3D-CRT) vs. intensity-modulated radiotherapy (IMRT) among patients treated in the prone position with the same fractionation and target of the hypofractionation arm of the Canadian/Whelan trial. Methods and Materials: An institutional review board-approved protocol identified a consecutive series of early-stage breast cancer patients treated according to the Canadian hypofractionation regimen but in the prone position. Patients underwent IMRT treatment planning and treatment if the insurance carrier approved reimbursement for IMRT; in case of refusal, a 3D-CRT plan was used. A comparison of the dosimetric and toxicity outcomes during the acute, subacute, and long-term follow-up of the two treatment groups is reported. Results: We included 97 consecutive patients with 100 treatment plans in this study (3 patients with bilateral breast cancer); 40 patients were treated with 3D-CRT and 57 with IMRT. IMRT significantly reduced the maximum dose (Dmax median, 109.96% for 3D-CRT vs. 107.28% for IMRT; p < 0.0001, Wilcoxon test) and improved median dose homogeneity (median, 1.15 for 3D-CRT vs. 1.05 for IMRT; p < 0.0001, Wilcoxon test) when compared with 3D-CRT. Acute toxicity consisted primarily of Grade 1 to 2 dermatitis and occurred in 92% of patients. Grade 2 dermatitis occurred in 13% of patients in the 3D-CRT group and 2% in the IMRT group. IMRT moderately decreased rates of acute pruritus (p = 0.03, chi-square test) and Grade 2 to 3 subacute hyperpigmentation (p = 0.01, Fisher exact test). With a minimum of 6 months' follow-up, the treatment was similarly well tolerated in either group, including among women with large breast volumes. Conclusion: Hypofractionated breast radiotherapy is well tolerated when treating patients in the prone position, even among those with large breast volumes. Breast IMRT significantly improves dosimetry but yields only a modest

  15. Radiation-induced chondrosarcomas: A case report with review of literature

    Directory of Open Access Journals (Sweden)

    Gupta G

    2010-01-01

    Full Text Available Radiation therapy has become an important component of various cancer treatments. The development of second malignancy as a result of radiation therapy is a well-known sinister complication. However, radiation-induced sarcomas (RIS are rare complications of radiation therapy. The timescale between completion of the radiotherapy and the development of a second malignancy, known as the latent period, can vary widely from as little as 5 years to 50 years later. Radiation-induced sarcomas per se are very rare and those with histomorphology of chondrosarcomas are even rarer. We report a rare case of RIS of left iliac bone in a 62-year-old lady after combined chemotherapy and external beam radiation therapy for cervical carcinoma (stage IIb. This case is being reported for its extreme rarity, vivid histology and clinical presentation.

  16. Hypofractionation results in reduced tumor cell kill compared to conventional fractionation for tumors with regions of hypoxia.

    Science.gov (United States)

    Carlson, David J; Keall, Paul J; Loo, Billy W; Chen, Zhe J; Brown, J Martin

    2011-03-15

    Tumor hypoxia has been observed in many human cancers and is associated with treatment failure in radiation therapy. The purpose of this study is to quantify the effect of different radiation fractionation schemes on tumor cell killing, assuming a realistic distribution of tumor oxygenation. A probability density function for the partial pressure of oxygen in a tumor cell population is quantified as a function of radial distance from the capillary wall. Corresponding hypoxia reduction factors for cell killing are determined. The surviving fraction of a tumor consisting of maximally resistant cells, cells at intermediate levels of hypoxia, and normoxic cells is calculated as a function of dose per fraction for an equivalent tumor biological effective dose under normoxic conditions. Increasing hypoxia as a function of distance from blood vessels results in a decrease in tumor cell killing for a typical radiotherapy fractionation scheme by a factor of 10(5) over a distance of 130 μm. For head-and-neck cancer and prostate cancer, the fraction of tumor clonogens killed over a full treatment course decreases by up to a factor of ∼10(3) as the dose per fraction is increased from 2 to 24 Gy and from 2 to 18 Gy, respectively. Hypofractionation of a radiotherapy regimen can result in a significant decrease in tumor cell killing compared to standard fractionation as a result of tumor hypoxia. There is a potential for large errors when calculating alternate fractionations using formalisms that do not account for tumor hypoxia. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Bystander effects in UV-induced genomic instability: Antioxidants inhibit delayed mutagenesis induced by ultraviolet A and B radiation

    Directory of Open Access Journals (Sweden)

    Dahle Jostein

    2005-01-01

    Full Text Available Abstract Background Genomic instability is characteristic of many types of human cancer. Recently, we reported that ultraviolet radiation induced elevated mutation rates and chromosomal instability for many cell generations after ultraviolet irradiation. The increased mutation rates of unstable cells may allow them to accumulate aberrations that subsequently lead to cancer. Ultraviolet A radiation, which primarily acts by oxidative stress, and ultraviolet B radiation, which initially acts by absorption in DNA and direct damage to DNA, both produced genomically unstable cell clones. In this study, we have determined the effect of antioxidants on induction of delayed mutations by ultraviolet radiation. Delayed mutations are indicative of genomic instability. Methods Delayed mutations in the hypoxanthine phosphoribosyl transferase (hprt gene were detected by incubating the cells in medium selectively killing hprt mutants for 8 days after irradiation, followed by a 5 day period in normal medium before determining mutation frequencies. Results The UVB-induced delayed hprt mutations were strongly inhibited by the antioxidants catalase, reduced glutathione and superoxide dismutase, while only reduced glutathione had a significant effect on UVA-induced delayed mutations. Treatment with antioxidants had only minor effects on early mutation frequenies, except that reduced glutathione decreased the UVB-induced early mutation frequency by 24 %. Incubation with reduced glutathione was shown to significantly increase the intracellular amount of reduced glutathione. Conclusion The strong effects of these antioxidants indicate that genomic instability, which is induced by the fundamentally different ultraviolet A and ultraviolet B radiation, is mediated by reactive oxygen species, including hydrogen peroxide and downstream products. However, cells take up neither catalase nor SOD, while incubation with glutathione resulted in increased intracellular levels of

  18. Radiation-Induced Esophagitis is Mitigated by Soy Isoflavones

    Directory of Open Access Journals (Sweden)

    Matthew D Fountain

    2016-11-01

    Full Text Available Introduction: Lung cancer patients receiving radiotherapy present with acute esophagitis and chronic fibrosis, as a result of radiation injury to esophageal tissues. We have shown that soy isoflavones alleviate pneumonitis and fibrosis caused by radiation toxicity to normal lung. The effect of soy isoflavones on esophagitis histopathological changes induced by radiation was investigated. Methods: C57BL/6 mice were treated with 10 Gy or 25 Gy single thoracic irradiation and soy isoflavones for up to 16 weeks. Damage to esophageal tissues was assessed by H&E, Masson’s Trichrome and Ki-67 staining at 1, 4, 10, 16 weeks after radiation. The effects on smooth muscle cells and leukocyte infiltration were determined by immunohistochemistry using anti-αSMA and anti-CD45 respectively. Results: Radiation caused thickening of esophageal tissue layers that was significantly reduced by soy isoflavones. Major radiation alterations included hypertrophy of basal cells in mucosal epithelium and damage to smooth muscle cells in muscularis mucosae as well as disruption of collagen fibers in lamina propria connective tissue with leukocyte infiltration. These effects were observed as early as one week after radiation and were more pronounced with a higher dose of 25 Gy. Soy isoflavones limited the extent of tissue damage induced by radiation both at 10 and 25 Gy.Conclusions: Soy isoflavones have a radioprotective effect on the esophagus, mitigating the early and late effects of radiation injury in several esophagus tissue layers. Soy could be administered with radiotherapy to decrease the incidence and severity of esophagitis in lung cancer patients receiving thoracic radiation therapy.

  19. Dose rate effectiveness in radiation-induced teratogenesis in mice

    International Nuclear Information System (INIS)

    Kato, F.; Ootsuyama, A.; Norimura, T.

    2000-01-01

    To investigate the role of p53 gene in tissue repair of teratogenic injury, we compared incidence of radiation-induced malformations in homozygous p53(-/-) mice, heterozygous p53(+/-) mice and wild-type p53(+/+) mice. After X-irradiation with 2 Gy at high dose rate on 9.5 days of gestation, p53(-/-) mice showed higher incidences of anomalies and higher resistance to prenatal deaths than p53(+/+) mice. This reciprocal relationship of radiosensitivity to anomalies and deaths supports the notion that embryos or fetuses have a p53-dependent 'guardian' that aborts cells bearing radiation-induced teratogenic DNA damage. In fact, after X-irradiation, the number of apoptotic cells was greatly increased in p53(+/+) fetuses but not in p53(-/-) fetuses. The same dose of γ-ray exposure at low dose rate on 9.5-10.5 day of gestation produced significant reduction of radiation-induced malformation in p53(+/+) and p53(+/-) mice, remained teratogenic for p53(-/-) mice. These results suggest that complete elimination of teratogenic damage from irradiated tissues requires the concerted cooperation of two mechanisms; proficient DNA repair and the p53-dependent apoptotic tissue repair. When concerted DNA repair and apoptosis functions efficiently, there is a threshold dose-rate for radiation-induced malformations. (author)

  20. Radiation-induced premature menopause: a misconception

    International Nuclear Information System (INIS)

    Madsen, Berit L.; Giudice, Linda; Donaldson, Sarah S.

    1995-01-01

    Purpose: To disprove the common view that women who have undergone irradiation to fields excluding the pelvis are at risk for radiation-induced premature menopause, we reviewed menstrual function and fertility among women treated with subtotal lymphoid irradiation for Hodgkin's Disease. Methods and Materials: Treatment and follow-up records of all women less than age 50 at the time of diagnosis of Stage I or II supradiaphragmatic Hodgkin's Disease, treated with subtotal lymphoid irradiation alone and enrolled in radiotherapy trials from 1967 to 1985, were reviewed. In addition, patients were surveyed regarding their menstrual status and fertility history. Results: Thirty-six women, aged 10 to 40 years, with normal menstrual function at the time of Hodgkin's diagnosis, were identified. Mean follow-up was 14 years, with a range of 1.25-22.75 years. The average radiation dose to mantle and paraaortic fields was 40-44 Gy; the calculated scatter radiation dose to the pelvis at the ovaries was 3.2 Gy. There were 38 pregnancies in 18 women; all offspring are normal. One of 36 women (2.7%) experienced premature menopause. The reported rate of premature menopause in women who have not undergone irradiation is 1-3%; not significantly different than the rate in our study. There is a syndrome whereby antibodies to several endocrine organs occur (including the ovary), which is associated with premature ovarian failure. This syndrome may be associated with prior radiation to the thyroid, such as that given by mantle-irradiation for Hodgkin's Disease. We report such a case. Conclusion: There is little risk of premature menopause in women treated with radiation fields that exclude the pelvis. Women with presumed radiation-induced premature menopause warrant an evaluation to exclude other causes of ovarian failure, such as autoimmune disorders

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

    Science.gov (United States)

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

    2006-01-01

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

  2. Better flocculants by radiation induced polymerization

    International Nuclear Information System (INIS)

    Laizier, J.; Gaussens, G.

    1978-01-01

    The use of radiation induced polymerization should theoritically allow to prepare better flocculants. The testings of several products prepared by such a process shows that better properties are indeed obtained: better efficiencies, lower amounts needed, better overall properties [fr

  3. Effect of epicatechin against radiation-induced oral mucositis: in vitro and in vivo study.

    Directory of Open Access Journals (Sweden)

    Yoo Seob Shin

    Full Text Available PURPOSE: Radiation-induced oral mucositis limits the delivery of high-dose radiation to head and neck cancer. This study investigated the effectiveness of epicatechin (EC, a component of green tea extracts, on radiation-induced oral mucositis in vitro and in vivo. EXPERIMENTAL DESIGN: The effect of EC on radiation-induced cytotoxicity was analyzed in the human keratinocyte line HaCaT. Radiation-induced apoptosis, change in mitochondrial membrane potential (MMP, reactive oxygen species (ROS generation and changes in the signaling pathway were investigated. In vivo therapeutic effects of EC for oral mucositis were explored in a rat model. Rats were monitored by daily inspections of the oral cavity, amount of oral intake, weight change and survival rate. For histopathologic evaluation, hematoxylin-eosin staining and TUNEL staining were performed. RESULTS: EC significantly inhibited radiation-induced apoptosis, change of MMP, and intracellular ROS generation in HaCaT cells. EC treatment markedly attenuated the expression of p-JNK, p-38, and cleaved caspase-3 after irradiation in the HaCaT cells. Rats with radiation-induced oral mucositis showed decreased oral intake, weight and survival rate, but oral administration of EC significantly restored all three parameters. Histopathologic changes were significantly decreased in the EC-treated irradiated rats. TUNEL staining of rat oral mucosa revealed that EC treatment significantly decreased radiation-induced apoptotic cells. CONCLUSIONS: This study suggests that EC significantly inhibited radiation-induced apoptosis in keratinocytes and rat oral mucosa and may be a safe and effective candidate treatment for the prevention of radiation-induced mucositis.

  4. The influence of infrared radiation on short-term ultraviolet-radiation-induced injuries

    International Nuclear Information System (INIS)

    Kaidbey, K.H.; Witkowski, T.A.; Kligman, A.M.

    1982-01-01

    Because heat has been reported to influence adversely short- and long-term ultraviolet (UV)-radiation-induced skin damage in animals, we investigated the short-term effects of infrared radiation on sunburn and on phototoxic reactions to topical methoxsalen and anthracene in human volunteers. Prior heating of the skin caused suppression of the phototoxic response to methoxsalen as evidenced by an increase in the threshold erythema dose. Heat administered either before or after exposure to UV radiation had no detectable influence on sunburn erythema or on phototoxic reactions provoked by anthracene

  5. Investigation of the role of oncornavirus in radiation-induced osteosarcomas

    International Nuclear Information System (INIS)

    Frazier, M.E.; Park, J.F.; Jee, W.S.S.; Taylor, G.

    1975-01-01

    Viruses of the RNA tumor group are etiologic agents of spontaneously occurring neoplastic disease in a number of animal species. These oncornaviruses possess certain biochemical properties which permit them to be easily detected in infected cells, including RNA-instructed DNA polymerase (RIDP) and a closely associated 70S RNA genome in a cytoplasmic particulate fraction having a density of 1.15-1.20 g/ml. Tissues from three dogs with radiation-induced lung tumors and four dogs without tumors did not contain RIDP. However, RIDP was detected in materials prepared from five beagles with radiation-induced osteosarcomas. The presence of RIDP in these radiation-induced osteosarcomas can be considered indicative of retravirus or oncornavirus infection

  6. Radiation-induced cationic curing of vinyl ethers

    International Nuclear Information System (INIS)

    Lapin, S.C.

    1992-01-01

    Recently there has been an increasing interest in nonacrylate radiation-curable coatings. Vinyl ethers are particularly reactive under cationic polymerization reaction conditions. The high efficiency of the photoacid initiators combined with the high reactivity of vinyl ether monomers makes this a potentially very useful system. This chapter discusses the preparation of vinyl ethers, introduces vinyl ether-functional monomers and oligomers, describes radiation-induced cationic polymerization of vinyl ethers, and discusses various coating systems. Throughout the chapter, an emphasis is placed on radiation-curable coating applications. 64 refs., 5 figs., 11 tabs

  7. Radiation-induced life-shortening and premature aging

    International Nuclear Information System (INIS)

    Walburg, H.E. Jr.

    1975-01-01

    Data from a number of studies on irradiated laboratory animals showed that almost none of the characteristic lesions associated with senescence that were studied adequately reflects a radiation effect analogous to premature aging. In fact, most of the age-related changes showed no effect of radiation at all, and many of those that did (for example, graying of hair, sterility, cataract formation) did not appear to be due to similar mechanisms. It is concluded that, in the light of more recent information, the hypothesis of radiation-induced premature aging requires reassessment. (80 references) (CH)

  8. Incorporating Cancer Stem Cells in Radiation Therapy Treatment Response Modeling and the Implication in Glioblastoma Multiforme Treatment Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Victoria Y.; Nguyen, Dan; Pajonk, Frank; Kupelian, Patrick; Kaprealian, Tania; Selch, Michael; Low, Daniel A.; Sheng, Ke, E-mail: ksheng@mednet.ucla.edu

    2015-03-15

    Purpose: To perform a preliminary exploration with a simplistic mathematical cancer stem cell (CSC) interaction model to determine whether the tumor-intrinsic heterogeneity and dynamic equilibrium between CSCs and differentiated cancer cells (DCCs) can better explain radiation therapy treatment response with a dual-compartment linear-quadratic (DLQ) model. Methods and Materials: The radiosensitivity parameters of CSCs and DCCs for cancer cell lines including glioblastoma multiforme (GBM), non–small cell lung cancer, melanoma, osteosarcoma, and prostate, cervical, and breast cancer were determined by performing robust least-square fitting using the DLQ model on published clonogenic survival data. Fitting performance was compared with the single-compartment LQ (SLQ) and universal survival curve models. The fitting results were then used in an ordinary differential equation describing the kinetics of DCCs and CSCs in response to 2- to 14.3-Gy fractionated treatments. The total dose to achieve tumor control and the fraction size that achieved the least normal biological equivalent dose were calculated. Results: Smaller cell survival fitting errors were observed using DLQ, with the exception of melanoma, which had a low α/β = 0.16 in SLQ. Ordinary differential equation simulation indicated lower normal tissue biological equivalent dose to achieve the same tumor control with a hypofractionated approach for 4 cell lines for the DLQ model, in contrast to SLQ, which favored 2 Gy per fraction for all cells except melanoma. The DLQ model indicated greater tumor radioresistance than SLQ, but the radioresistance was overcome by hypofractionation, other than the GBM cells, which responded poorly to all fractionations. Conclusion: The distinct radiosensitivity and dynamics between CSCs and DCCs in radiation therapy response could perhaps be one possible explanation for the heterogeneous intertumor response to hypofractionation and in some cases superior outcome from

  9. Incorporating Cancer Stem Cells in Radiation Therapy Treatment Response Modeling and the Implication in Glioblastoma Multiforme Treatment Resistance

    International Nuclear Information System (INIS)

    Yu, Victoria Y.; Nguyen, Dan; Pajonk, Frank; Kupelian, Patrick; Kaprealian, Tania; Selch, Michael; Low, Daniel A.; Sheng, Ke

    2015-01-01

    Purpose: To perform a preliminary exploration with a simplistic mathematical cancer stem cell (CSC) interaction model to determine whether the tumor-intrinsic heterogeneity and dynamic equilibrium between CSCs and differentiated cancer cells (DCCs) can better explain radiation therapy treatment response with a dual-compartment linear-quadratic (DLQ) model. Methods and Materials: The radiosensitivity parameters of CSCs and DCCs for cancer cell lines including glioblastoma multiforme (GBM), non–small cell lung cancer, melanoma, osteosarcoma, and prostate, cervical, and breast cancer were determined by performing robust least-square fitting using the DLQ model on published clonogenic survival data. Fitting performance was compared with the single-compartment LQ (SLQ) and universal survival curve models. The fitting results were then used in an ordinary differential equation describing the kinetics of DCCs and CSCs in response to 2- to 14.3-Gy fractionated treatments. The total dose to achieve tumor control and the fraction size that achieved the least normal biological equivalent dose were calculated. Results: Smaller cell survival fitting errors were observed using DLQ, with the exception of melanoma, which had a low α/β = 0.16 in SLQ. Ordinary differential equation simulation indicated lower normal tissue biological equivalent dose to achieve the same tumor control with a hypofractionated approach for 4 cell lines for the DLQ model, in contrast to SLQ, which favored 2 Gy per fraction for all cells except melanoma. The DLQ model indicated greater tumor radioresistance than SLQ, but the radioresistance was overcome by hypofractionation, other than the GBM cells, which responded poorly to all fractionations. Conclusion: The distinct radiosensitivity and dynamics between CSCs and DCCs in radiation therapy response could perhaps be one possible explanation for the heterogeneous intertumor response to hypofractionation and in some cases superior outcome from

  10. Radiation-induced electron paramagnetic resonance signal and soybean isoflavones content

    International Nuclear Information System (INIS)

    Oliveira, Marcos R.R. de; Mandarino, José M.G.; Mastro, Nelida L. del

    2012-01-01

    Electron Paramagnetic Resonance (EPR) is a well-known spectroscopic technique that detects paramagnetic centers and can detect free radicals with high sensitivity. In food, free radicals can be generated by several commonly used industrial processes, such as radiosterilization or heat treatment. EPR spectroscopy is used to detect radioinduced free radicals in food. In this work the relation between EPR signal induced by gamma irradiation treatment and soybean isoflavones content was investigated. Present results did not show correlation between total isoflavones content and the EPR signal. Nevertheless, some isoflavone contents had a negative correlation with the radiation-induced EPR signal. - Highlights: ► Electron Paramagnetic Resonance (EPR) detects free radicals. ► Ionizing radiation as free radicals inducer. ► Total soybean isoflvones do not correlate with radiation-induced EPR intensity but a soybean glucosyl glucoside isoflavone does.

  11. Total-dose radiation-induced degradation of thin film ferroelectric capacitors

    International Nuclear Information System (INIS)

    Schwank, J.R.; Nasby, R.D.; Miller, S.L.; Rodgers, M.S.; Dressendorfer, P.V.

    1990-01-01

    Thin film PbZr y Ti 1-y O 3 (PZT) ferroelectric memories offer the potential for radiation-hardened, high-speed nonvolatile memories with good retention and fatigue properties. In this paper we explore in detail the radiation hardness of PZT ferroelectric capacitors. Ferroelectric capacitors were irradiated using x-ray and Co-60 sources to dose levels up to 16 Mrad(Si). The capacitors were characterized for their memory properties both before and after irradiation. The radiation hardness was process dependent. Three out of four processes resulted in capacitors that showed less than 30% radiation-induced degradation in retained polarization charge and remanent polarization after irradiating to 16 Mrad(Si). On the other hand, one of the processes showed significant radiation-induced degradation in retained polarization charge and remanent polarization at dose levels above 1 Mrad(Si). The decrease in retained polarization charge appears to be due to an alteration of the switching characteristics of the ferroelectric due to changes in the internal fields. The radiation-induced degradation is recoverable by a postirradiation biased anneal and can be prevented entirely if devices are cycled during irradiation. The authors have developed a model to simulate the observed degradation

  12. Effects of an Amifostine analogue on radiation induced lung inflammation and fibrosis

    International Nuclear Information System (INIS)

    Arora, Aastha; Bhuria, Vikas; Soni, Ravi; Singh, Saurabh; Hazari, Puja Panwar; Bhatt, Anant Narayan; Dwarakanath, B.S.; Pathak, Uma; Mathur, Shweta; Sandhir, Rajat

    2014-01-01

    Radiation-induced pulmonary toxicity causes significant morbidity and mortality in patients irradiated for thoracic malignancies as well as in victims of accidental radiation exposure. We have recently established the efficacy of an analogue of Amifostine (DRDE-30) in reducing the mortality of whole body irradiated mice. The widely used radioprotector Amifostine has been found to reduce the incidence of radiation induced pneumonitis during radiation therapy for non small cell lung carcinoma. In the present study, we investigated the potential of DRDE-30 in ameliorating the radiation induced lung damage. Intra-peritoneal administration of DRDE-30 at 220 mg/kg b.wt 30 min. prior to 13.5 Gy thoracic radiation enhanced the 24-month survival of C57BL/6 mice to 80% compared to 0% with radiation alone. Reduced protein content and cell number in the broncheo-alveolar lavage fluid suggested reduction in radiation induced vascular permeability in DRDE-30 treated mice. Higher levels of MnSOD and Catalase observed under these conditions indicated that strengthening of the anti-oxidant defense system by DRDE-30 could also contribute to the protection against radiation induced lung damage. Reduced levels of p-p38 observed under these conditions suggested down-regulation of the p38/MAP kinase pathway as one of the plausible mechanisms underlying anti-inflammatory effects of DRDE-30, while lower levels of Vimentin seen, indicated inhibition of epithelial to mesenchymal transition revealing its anti-fibrotic effect as well. Structural analysis with X-ray CT indicated comparable lung architecture in control and drug treated mice in terms of reduced opacity, which correlated well with the lung morphology (H and E staining) and reduced collagen deposition (trichrome staining). These results demonstrate the potential of DRDE-30 in reducing radiation induced pulmonary toxicity by attenuating the inflammatory and fibrotic responses. (author)

  13. Naturally occurring and radiation-induced tumors in SPF mice, and genetic influence in radiation leukemogenesis

    International Nuclear Information System (INIS)

    Kasuga, T.

    1979-01-01

    The data obtained so far in this study point to a strong genetic influence not only on the types and incidence of naturally occurring and radiation-induced tumors but also on radiation leukemogenesis. (Auth.)

  14. Radiation-induced-radioresistance: mechanisms and modification radioprotection

    International Nuclear Information System (INIS)

    Bala, Madhu

    2005-01-01

    Full text: The term radiation-induced-radioresistance (RIR) has been chosen to explain a particular class of resistance against lethal doses of radiation, which is transient and is induced by pre-exposure to low doses of radiation. This is a genetically governed phenomenon and is different from adaptation which in one of its several senses, refers to evolutionary transformation into new behavioural patterns. RIR is understood to be an evolutionarily conserved fundamental cellular defense mechanism. Small doses of radiation acting as stress stimuli evoke a concerted action of molecular pathways which help the organism to cope-up with the genotoxic effects of lethal doses of radiation given subsequently. Such molecular pathways are a complex interplay of genetic and biochemical entities and are increasingly becoming the focus of research world over. Most of our information on this subject has been gathered from prokaryotes, simpler eukaryotes, human cells and the epidemiological studies. A number of genes such as GADD 45, CDKN1A, PBP74, DIR1, DDR have been reported by to participate in RIR. However, till date, the mechanism of RIR remain poorly understood. In this deliberation some of our findings on mechanisms of RIR will be presented. Further, modification of RIR by a metabolic modifier, presently under clinical investigations for tumor radiotherapy, will also be presented

  15. Radiation-induced malignant tumours: a specific cytogenetic profile?

    International Nuclear Information System (INIS)

    Chauveinc, L.; Gaboriaux, G.; Dutrillaux, A. M.; Dutrillaux, B.; Chauveinc, L.; Ricoul, M.; Sabatier, L.; Dutrillaux, B.

    1997-01-01

    To date, there is no criterion enabling to determine the spontaneous or radio-induced origin of malignant tumour occurring in a previously irradiated patient. Biological studies are rare. The cytogenetic data which could be found in the literature for eleven radio-induced tumours suggest that aneuploidies and polyclonality are frequent events. We studied, by R-Banding cytogenetic technique, five patients with short-term cultures (3 cases), short and long-term cultures (1 case) and xeno-grafting on nude pattern a high rate of balanced translocations, numerous random break points and a polyclonal evolution (10 clones). All other tumours, including the xeno-grafting sarcoma, had a monoclonal profile with complex karyotypes, hypo-diploid formulas and many deletions. These results show that the mechanism of radiation-induced tumours frequently involves chromosomes losses and deletions. The most likely explanation is that these alterations unmask radiation induced recessive mutations of tumour suppressor genes. (authors)

  16. Effects of ceramide inhibition on radiation-induced apoptosis in human leukemia MOLT-4 cells

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Eriko; Inanami, Osamu; Asanuma, Taketoshi; Kuwabara, Mikinori [Hokkaido Univ., Graduate School of Veterinary Medicine, Sapporo, Hokkaido (Japan)

    2006-03-15

    In the present study, using inhibitors of ceramide synthase (fumonisin B{sub 1}), ketosphinganine synthetase (L-cycloserine), acid sphingomyelinase (D609 and desipramine) and neutral sphingomyelinase (GW4869), the role of ceramide in X-ray-induced apoptosis was investigated in MOLT-4 cells. The diacylglycerol kinase (DGK) assay showed that the intracellular concentration of ceramide increased time-dependently after X irradiation of cells, and this radiation-induced accumulation of ceramide did not occur prior to the appearance of apoptotic cells. Treatment with D609 significantly inhibited radiation-induced apoptosis, but did not inhibit the increase of intracellular ceramide. Treatment with desipramine or GW4869 prevented neither radiation-induced apoptosis nor the induced increase of ceramide. On the other hand, fumonisin B{sub 1} and L-cycloserine had no effect on the radiation-induced induction of apoptosis, in spite of significant inhibition of the radiation-induced ceramide. From these results, it was suggested that the increase of the intracellular concentration of ceramide was not essential for radiation-induced apoptosis in MOLT-4 cells. (author)

  17. Effects of ceramide inhibition on radiation-induced apoptosis in human leukemia MOLT-4 cells

    International Nuclear Information System (INIS)

    Takahashi, Eriko; Inanami, Osamu; Asanuma, Taketoshi; Kuwabara, Mikinori

    2006-01-01

    In the present study, using inhibitors of ceramide synthase (fumonisin B 1 ), ketosphinganine synthetase (L-cycloserine), acid sphingomyelinase (D609 and desipramine) and neutral sphingomyelinase (GW4869), the role of ceramide in X-ray-induced apoptosis was investigated in MOLT-4 cells. The diacylglycerol kinase (DGK) assay showed that the intracellular concentration of ceramide increased time-dependently after X irradiation of cells, and this radiation-induced accumulation of ceramide did not occur prior to the appearance of apoptotic cells. Treatment with D609 significantly inhibited radiation-induced apoptosis, but did not inhibit the increase of intracellular ceramide. Treatment with desipramine or GW4869 prevented neither radiation-induced apoptosis nor the induced increase of ceramide. On the other hand, fumonisin B 1 and L-cycloserine had no effect on the radiation-induced induction of apoptosis, in spite of significant inhibition of the radiation-induced ceramide. From these results, it was suggested that the increase of the intracellular concentration of ceramide was not essential for radiation-induced apoptosis in MOLT-4 cells. (author)

  18. Free radicals in wood induced by γ-radiation

    International Nuclear Information System (INIS)

    Xu Honglin; Zhang Wenhui

    1994-01-01

    The free radicals in wood induced by γ-radiation were studied by electron spin resonance. The fine structure of the ESR signal from sawdust samples irradiated could be resolved into various radicals. These free radicals have a very long lifetime. The major spectrum for the free radicals will exponentially increased along with the radiation dose according to Y 1-Exp(-α a D). The intensity of radiation radicals is dependent on tree species. The stronger the intensity of mechanic free radicals is, the stronger the intensity of radiation free radicals

  19. Laser radiation effect on radiation-induced defects in heavy ion tracks in dielectrics

    International Nuclear Information System (INIS)

    Egorov, A.N.; Zhiryakov, B.M.; Kushin, V.V.; Lyapidevskij, V.K.; Khokhlov, N.B.

    1988-01-01

    Possibility of laser radiation resonance effect on radiation-induced defects in heavy ion tracks in dielectric materials is investigated. Absorption spectra in infrared, visible and ultraviolet ranges for cellulose nitrate samples irradiated by 6 MeV/nucleon 58 Ni ions and reactor gamma radiation are measured. Absorption spectra for irradiated and reference samples are presented. Two absorption bands λ 1 =0.33 μm (E 1 =3.9 eV) and λ 2 =0.72 μm (E 2 =1.7 eV) are detected. Etching rate decrease in a track under laser radiation effect is noticed. 3 refs.; 1 fig

  20. Anti-apoptotic peptides protect against radiation-induced cell death

    International Nuclear Information System (INIS)

    McConnell, Kevin W.; Muenzer, Jared T.; Chang, Kathy C.; Davis, Chris G.; McDunn, Jonathan E.; Coopersmith, Craig M.; Hilliard, Carolyn A.; Hotchkiss, Richard S.; Grigsby, Perry W.; Hunt, Clayton R.

    2007-01-01

    The risk of terrorist attacks utilizing either nuclear or radiological weapons has raised concerns about the current lack of effective radioprotectants. Here it is demonstrated that the BH4 peptide domain of the anti-apoptotic protein Bcl-xL can be delivered to cells by covalent attachment to the TAT peptide transduction domain (TAT-BH4) and provide protection in vitro and in vivo from radiation-induced apoptotic cell death. Isolated human lymphocytes treated with TAT-BH4 were protected against apoptosis following exposure to 15 Gy radiation. In mice exposed to 5 Gy radiation, TAT-BH4 treatment protected splenocytes and thymocytes from radiation-induced apoptotic cell death. Most importantly, in vivo radiation protection was observed in mice whether TAT-BH4 treatment was given prior to or after irradiation. Thus, by targeting steps within the apoptosis signaling pathway it is possible to develop post-exposure treatments to protect radio-sensitive tissues

  1. SU-F-J-130: Margin Determination for Hypofractionated Partial Breast Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Geady, C [Ryerson University (Canada); Keller, B; Hahn, E; Vesprini, D; Soliman, H; Lee, J [University of Toronto, Sunnybrook Health Sciences Center, Toronto, Ontario (Canada); Ruschin, M; McCann, C [University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Makhani, N; Bosnic, S [Sunnybrook Health Sciences Center, Toronto, Ontario (Canada)

    2016-06-15

    Purpose: To determine the Planning Target Volume (PTV) margin for Hypofractionated Partial Breast Irradiation (HPBI) using the van Herk formalism (M=2.5∑+0.7σ). HPBI is a novel technique intended to provide local control in breast cancer patients not eligible for surgical resection, using 40 Gy in 5 fractions prescribed to the gross disease. Methods: Setup uncertainties were quantified through retrospective analysis of cone-beam computed tomography (CBCT) data sets, collected prior to (prefraction) and after (postfraction) treatment delivery. During simulation and treatment, patients were immobilized using a wing board and an evacuated bag. Prefraction CBCT was rigidly registered to planning 4-dimensional computed tomography (4DCT) using the chest wall and tumor, and translational couch shifts were applied as needed. This clinical workflow was faithfully reproduced in Pinnacle (Philips Medical Systems) to yield residual setup and intrafractional error through translational shifts and rigid registrations (ribs and sternum) of prefraction CBCT to 4DCT and postfraction CBCT to prefraction CBCT, respectively. All ten patients included in this investigation were medically inoperable; the median age was 84 (range, 52–100) years. Results: Systematic (and random) setup uncertainties (in mm) detected for the left-right, craniocaudal and anteroposterior directions were 0.4 (1.5), 0.8 (1.8) and 0.4 (1.0); net uncertainty was determined to be 0.7 (1.5). Rotations >2° in any axis occurred on 8/72 (11.1%) registrations. Conclusion: Preliminary results suggest a non-uniform setup margin (in mm) of 2.2, 3.3 and 1.7 for the left-right, craniocaudal and anteroposterior directions is required for HPBI, given its immobilization techniques and online setup verification protocol. This investigation is ongoing, though published results from similar studies are consistent with the above findings. Determination of margins in breast radiotherapy is a paradigm shift, but a necessary

  2. Attenuation of a radiation-induced conditioned taste aversion after the development of ethanol tolerance

    International Nuclear Information System (INIS)

    Hunt, W.A.; Rabin, B.M.

    1988-01-01

    An attempt to reduce a radiation-induced conditioned taste aversion (CTA) was undertaken by rendering animals tolerant to ethanol. Ethanol tolerance, developed over 5 days, was sufficient to block a radiation-induced taste aversion, as well as an ethanol-induced CTA. Several intermittent doses of ethanol, which did not induce tolerance but removed the novelty of the conditioning stimulus, blocked an ethanol-induced CTA but not the radiation-induced CTA. A CTA induced by doses of radiation up to 500 rads was attenuated. These data suggest that radioprotection developing in association with ethanol tolerance is a result of a physiological response to the chronic presence of ethanol not to the ethanol itself

  3. PAI-1-dependent endothelial cell death determines severity of radiation-induced intestinal injury.

    Directory of Open Access Journals (Sweden)

    Rym Abderrahmani

    Full Text Available Normal tissue toxicity still remains a dose-limiting factor in clinical radiation therapy. Recently, plasminogen activator inhibitor type 1 (SERPINE1/PAI-1 was reported as an essential mediator of late radiation-induced intestinal injury. However, it is not clear whether PAI-1 plays a role in acute radiation-induced intestinal damage and we hypothesized that PAI-1 may play a role in the endothelium radiosensitivity. In vivo, in a model of radiation enteropathy in PAI-1 -/- mice, apoptosis of radiosensitive compartments, epithelial and microvascular endothelium was quantified. In vitro, the role of PAI-1 in the radiation-induced endothelial cells (ECs death was investigated. The level of apoptotic ECs is lower in PAI-1 -/- compared with Wt mice after irradiation. This is associated with a conserved microvascular density and consequently with a better mucosal integrity in PAI-1 -/- mice. In vitro, irradiation rapidly stimulates PAI-1 expression in ECs and radiation sensitivity is increased in ECs that stably overexpress PAI-1, whereas PAI-1 knockdown increases EC survival after irradiation. Moreover, ECs prepared from PAI-1 -/- mice are more resistant to radiation-induced cell death than Wt ECs and this is associated with activation of the Akt pathway. This study demonstrates that PAI-1 plays a key role in radiation-induced EC death in the intestine and suggests that this contributes strongly to the progression of radiation-induced intestinal injury.

  4. Breast cancer induced by protracted radiation exposures

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1997-01-01

    The experience at Hiroshima/Nagasaki demonstrated that breast cancer can be induced by single doses of ionizing radiation following latencies of 10-40 years. Several epidemiological studies, usually involving ancillary low-LET radiation to the breast, have demonstrated that breast cancer can be induced by protracted exposures, with similar latencies, and with similar dependencies on dose. Radiobiologically these results suggest that the target cells involved were deficient in repair of low-LET damage even when the protraction was over months to years. Since three-quarters of breast tumors originate in the ducts where their proliferation is controlled by menstrual-cycle timed estrogen/progesterone secretions, these cells periodically were in cycle. Thus, the two main elements of a conceptual model for radon-induced lung cancer -- kinetics and deficient repair -- are satisfied. The model indicates that breast cancer could be the cumulative effect of protracted small exposures, the risk from any one of which ordinarily would be quite small. (author)

  5. Radiation-induced void swelling in metals and alloys

    International Nuclear Information System (INIS)

    Zelinskij, V.F.; Neklyudov, I.M.; Ozhigov, L.S.; Reznichenko, Eh.A.; Rozhkov, V.V.; Chernyaeva, T.T.

    1979-01-01

    Main regularities in the development of radiation-induced void swelling are considered. Special attention is paid to consideration of a possibility to obtain information on material behaviour under conditions of reactor irradiation proceeding from the data of simulation experiments and to methods of rate control, for the processes which occur in material during irradiation and further annealing by the way of rationalized alloying, of thermomechanical treatment and programmed change of irradiation conditions under operation. Problems of initiation and growth of voids in irradiated materials are discussed as well as the ways to decrease the rate of radiation-induced void swelling

  6. Radiation-induced attenuation in integrated optical materials

    International Nuclear Information System (INIS)

    Evans, B.D.

    1989-01-01

    This paper reports that three materials commonly employed in opto-electronic integrated circuits evaluated for radiation-induced optical attenuation in the range 300 nm to 3000 nm. These include optically clear epoxy and crystalline lithium niobate after Co-60 exposure and crystalline tellurium dioxide after mixed gamma/fast-neutron exposure. In all these materials, however, induced loss was restricted to shorter wavelengths; attenuation induced at the telecommunications windows near 850, 1300 and 1550 nm was <0.1 dB/cm

  7. Radiation-induced tritium labelling and product analysis

    Energy Technology Data Exchange (ETDEWEB)

    Peng, C.T. (California Univ., San Francisco, CA (United States). Dept. of Pharmaceutical Chemistry)

    1993-05-01

    By-products formed in radiation-induced tritium labelling are identified by co-chromatography with authentic samples or by structure prediction using a quantitative structure-retention index relationship. The by-products, formed from labelling of steroids, polynuclear aromatic hydrocarbons, 7-membered heterocyclic ring structures, 1,4-benzodiazepines, 1-haloalkanes, etc. with activated tritium and adsorbed tritium, are shown to be specifically labelled and anticipated products from known chemical reactions. From analyses of the by-products, one can conclude that the hydrogen abstraction by tritium atoms and the substitution by tritium ions are the mechanisms of labelling. Classification of the tritium labelling methods, on the basis of the type of tritium reagent, clearly shows the active role played by tritium atoms and ions in radiation-induced methods. (author).

  8. Second primary tumor and radiation induced neoplasma in the uterine cancer

    International Nuclear Information System (INIS)

    Sakurai, Tomoyasu; Nishio, Masamichi; Kagami, Yoshikazu; Murakami, Yoshitaka; Narimatsu, Naoto; Kanemoto, Toshitaka

    1984-01-01

    This report is concerned with multiple primary cancers developing in invasive uterine cancer. Second primary tumors were recorded 27 women with a total of 30 non-uterine cancer (exception of radiation-induced cancer). 17 patients of radiation-induced neoplasm were observed (Rectal cancer 4, soft part sarcoma 4, cancer of urinary bladder 3, bone tumor 3, uterin cancer 2 and cancer of Vulva 1). One case is 4 legions (corpus, sigma, thymoma and stomach), 2 cases are 3 lesions (uterine cervix, stomach and maxillay siuis: uterine cervix, thyroidal gland and radiation-induced soft part sarcoma). Only 5 of these 17 patients were known irradiated dose (50 Gy--55 Gy), however others unknown. The mean latent periods of 17 cases of radiation induced neoplasms are 19.4 years. 16 patients of late second cancers of the cervix appearing from 11 to 36 years (average 19.5 years) after initial radiotherapy were recorded. (author)

  9. Radiobiological evaluation of the radiation dose as used in high-precision radiotherapy. Effect of prolonged delivery time and applicability of the linear-quadratic model

    International Nuclear Information System (INIS)

    Shibamoto, Yuta; Otsuka, Shinya; Iwata, Hiromitsu; Sugie, Chikao; Ogino, Hiroyuki; Tomita, Natsuo

    2012-01-01

    Since the dose delivery pattern in high-precision radiotherapy is different from that in conventional radiation, radiobiological assessment of the physical dose used in stereotactic irradiation and intensity-modulated radiotherapy has become necessary. In these treatments, the daily dose is usually given intermittently over a time longer than that used in conventional radiotherapy. During prolonged radiation delivery, sublethal damage repair takes place, leading to the decreased effect of radiation. This phenomenon is almost universarily observed in vitro. In in vivo tumors, however, this decrease in effect can be counterbalanced by rapid reoxygenation, which has been demonstrated in a laboratory study. Studies on reoxygenation in human tumors are warranted to better evaluate the influence of prolonged radiation delivery. Another issue related to radiosurgery and hypofractionated stereotactic radiotherapy is the mathematical model for dose evaluation and conversion. Many clinicians use the linear-quadratic (LQ) model and biologically effective dose (BED) to estimate the effects of various radiation schedules, but it has been suggested that the LQ model is not applicable to high doses per fraction. Recent experimental studies verified the inadequacy of the LQ model in converting hypofractionated doses into single doses. The LQ model overestimates the effect of high fractional doses of radiation. BED is particularly incorrect when it is used for tumor responses in vivo, since it does not take reoxygenation into account. For normal tissue responses, improved models have been proposed, but, for in vivo tumor responses, the currently available models are not satisfactory, and better ones should be proposed in future studies. (author)

  10. Establishment of a Radiation-Induced Fibrosis Model in BALB/c Mice

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Seung Hee; Lee, Sang Wook; Moon, Soo Young; Oh, Jeong Yoon; Yang, Youn Joo; Park, Jin Hong [Dept. of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2010-11-15

    Although radiation-induced fibrosis is one of the common sequelae occurring after irradiation of skin and soft tissues, the treatment methods are not well standardized. This study aimed to establish the skin fibrosis mouse model by fractionated radiation for the further mechanism studies or testing the efficacy of therapeutic candidates. The right hind limbs of BALB/c mice received two fractions of 20 Gy using a therapeutic linear accelerator. Early skin damages were scored and tissue fibrosis was assessed by the measurement of a leg extension. Morphological changes were assessed by H and E staining and by Masson's Trichrome staining. TGF-{beta}1 expression from soft tissues was also detected by immunohistochemistry and PCR. Two fractions of 20 Gy irradiation were demonstrated as being enough to induce early skin damage effects such as erythema, mild skin dryness, dry and wet desquamation within several weeks of radiation. After 13 weeks of irradiation, the average radiation-induced leg contraction was 11.1 {+-} 6.2 mm. Morphologic changes in irradiated skin biopsies exhibited disorganized collagen and extracellular matrix fibers, as well as the accumulation of myofibroblasts compared to the non-irradiated skin. Moreover, TGF-{beta}1 expression in tissue was increased by radiation. These results show that two fractions of 20 Gy irradiation can induce skin fibrosis in BALB/c mice accompanied by other common characteristics of skin damages. This animal model can be a useful tool for studying skin fibrosis induced by radiation.

  11. Function and regulation of ATF 3 expression induced by ionizing radiation

    International Nuclear Information System (INIS)

    Fan, Feiyue; Wang, Yong; Du, Liqin; Zhan, Qimin

    2008-01-01

    Full text: Ionizing radiation results in a series of damages of mammalian cells as a genotoxic stress. There are some genes expressed after cells damaged, in which ATF 3, a member of ATF/CREB family of transcription factors, is one of them. In this report, we demonstrate that ATF 3 can be induced by ionizing radiation. The induction of ATF 3 protein requires normal status of p53 function in cells. There are some quantitative relationships between ATF 3 induction and dosages of radiation or time post-irradiation. In another word, ATF 3 expression induced by ionizing radiation present dose- and time-dependent. The regulation of ATF 3 expression refers to program of promoter and transcription. Radiation induces ATF 3 expression by activating the promoter and RNA transcription. In method of tetracycline-inducible system (tet-off), we have found that over-expression of ATF 3 protein brings caspase/PARP proteins into cleavage, which induces cell programmed death, and suppresses cell growth. Meanwhile, it was found that ATF 3 expression could slow down progression of cell from G 1 to S phase. It indicates ATF 3 protein might play a negative role in the control of cell cycle progression. It is very excited that expression of ATF 3 protein did not only suppress cell growth, but also demonstrated protecting effect of cell growth suppression resulting from ionizing radiation. It is suggested that ATF 3 protein might take part in the damage repair process of cells. (author)

  12. Patient outcomes of monotherapy with hypofractionated three-dimensional conformal radiation therapy for stage T2 or T3 non-small cell lung cancer: a retrospective study

    International Nuclear Information System (INIS)

    Sakaguchi, Masakuni; Maebayashi, Toshiya; Aizawa, Takuya; Ishibashi, Naoya; Fukushima, Shoko; Abe, Osamu; Saito, Tsutomu

    2016-01-01

    Hypofractionated three-dimensional conformal radiation therapy (3D-CRT) is a treatment option for patients with early-stage non-small cell lung cancer (NSCLC) who are medically unable to tolerate surgery and who are not amenable to treatment with stereotactic body radiotherapy. This study assessed the efficacy and safety of 3D-CRT as a monotherapy in patients with localized stage T2 or T3 NSCLC. This retrospective study consisted of 29 patients (20 males) aged 56–89 years (median, 76 years) with histologically confirmed NSCLC who underwent 3D-CRT between 2005 and 2014. The median duration of patient observation was 17.0 months (range, 1.0–64.0 months). Complete and partial responses occurred in 13.8 and 44.8 % of patients, respectively, and the overall response rate was 58.2 %. Meanwhile, the 1- and 3-year survival rates were 65.8 and 33.8 %, respectively. In T2 NSCLC, the median survival time (MST) was 12 months, and the 1- and 3-year survival rates were 62.4 and 21.4 %, respectively. In T3 NSCLC, the MST was 17 months, and the 1- and 3-year survival rates were 72.9 and 48.6 %, respectively. Severe toxicities (Common Terminology Criteria Grade 3) were not observed. The mean biologically effective dose required to improve local control exceeded 80 Gy (range, 67.2–96.0 Gy). These findings support a role for 3D-CRT as a treatment option for patients who refuse or could not tolerate surgical therapy with early-stage NSCLC. Although this was a small, retrospective study, it may form the basis for future, larger controlled studies on 3D-CRT as a monotherapy for NSCLC

  13. Radiation induced peroxidation in model lipid systems

    International Nuclear Information System (INIS)

    Dahlan, K.Z.B.H.M.

    1981-08-01

    In the studies of radiation induced lipid peroxidation, lecithin-liposomes and aqueous micellar solutions of sodium linoleate (or linoleic acid) have been used as models of lipid membrane systems. The liposomes and aqueous linoleate micelles were irradiated in the presence of O 2 and N 2 O/O 2 (80/20 v/v). The peroxidation was initiated using gamma radiation from 60 Co radiation source and was monitored by measuring the increase in absorbance of conjugated diene at 232 nm and by the thiobarbituric acid (TBA) test. The oxidation products were also identified by GLC and GLC-MS analysis. (author)

  14. Comparison of gamma radiation - induced effects in two human prostate cancer cells

    International Nuclear Information System (INIS)

    Vucic, V.; Adzic, M.; Ruzdijic, S.; Radojcic, M.B. . E-mail address of corresponding author: vesnav@vin.bg.ac.yu; Vucic, V.)

    2005-01-01

    In this study, the effects of gamma radiation on two hormone refractory human prostate cancer cell lines, DU 145 and PC-3, were followed. It was shown that gamma radiation induced significant inhibition of cell proliferation and viability in dose dependent manner. Antiproliferative effects of radiation were similar in both cell lines, and more pronounced than cytotoxic effects. In addition to that, PC-3 cell line was more resistant to radiation -induced cytotoxicity. (author)

  15. A case of radiation-induced cancer of the hypopharynx

    International Nuclear Information System (INIS)

    Miyamoto, Kouji; Shimizu, Yukio; Yura, Jirou; Itoh, Yasufumi; Ikeda, Tsuneko; Outsubo, Toshio; Saitou, Hitoshi

    2001-01-01

    We report a case of radiation-induced cancer of the hypopharynx in a 65-year-old woman. The patient had received radiation treatment for Basedow's disease for several years starting at the age of 10 years. On June 26, 1993, she was examined at our hospital because of hoarseness and dysphagia. On July 22, right lobectomy was performed for suspected thyroid cancer. During this operation, endoscopy revealed hypopharyngeal cancer. Twenty-two days after surgery, total pharyngolaryngectomy and total esophagectomy were performed and a pharyngogastrostomy and a permanent tracheostomy were created. Histologic examination revealed moderately differentiated squamous cell cancer. This case was diagnosed as radiation-induced caner according to the diagnostic criteria of Sakai. (author)

  16. A case of radiation-induced cancer of the hypopharynx

    Energy Technology Data Exchange (ETDEWEB)

    Miyamoto, Kouji; Shimizu, Yukio; Yura, Jirou; Itoh, Yasufumi; Ikeda, Tsuneko [Matsunami General Hospital, Kasamatsu, Gifu (Japan); Outsubo, Toshio; Saitou, Hitoshi

    2001-06-01

    We report a case of radiation-induced cancer of the hypopharynx in a 65-year-old woman. The patient had received radiation treatment for Basedow's disease for several years starting at the age of 10 years. On June 26, 1993, she was examined at our hospital because of hoarseness and dysphagia. On July 22, right lobectomy was performed for suspected thyroid cancer. During this operation, endoscopy revealed hypopharyngeal cancer. Twenty-two days after surgery, total pharyngolaryngectomy and total esophagectomy were performed and a pharyngogastrostomy and a permanent tracheostomy were created. Histologic examination revealed moderately differentiated squamous cell cancer. This case was diagnosed as radiation-induced caner according to the diagnostic criteria of Sakai. (author)

  17. Radiation-Induced Bystander Response: Mechanism and Clinical Implications

    OpenAIRE

    Suzuki, Keiji; Yamashita, Shunichi

    2014-01-01

    Significance: Absorption of energy from ionizing radiation (IR) to the genetic material in the cell gives rise to damage to DNA in a dose-dependent manner. There are two types of DNA damage; by a high dose (causing acute or deterministic effects) and by a low dose (related to chronic or stochastic effects), both of which induce different health effects. Among radiation effects, acute cutaneous radiation syndrome results from cell killing as a consequence of high-dose exposure.

  18. Imaging Features that Discriminate between Foci Induced by High- and Low-LET Radiation in Human Fibroblasts

    International Nuclear Information System (INIS)

    Costes, Sylvain V.; Boissiere, Arnaud; Ravani, Shraddha; Romano, Raquel; Parvin, Bahram; Barcellos-Hoff, Mary Helen

    2006-01-01

    In this study, we investigated the formation of radiation-induced foci in normal human fibroblasts exposed to X rays or 130 keV/mum nitrogen ions using antibodies to phosphorylated protein kinase ataxia telangiectasia mutated (ATMp) and histone H2AX(gamma-H2AX). High-content automatic image analysis was used to quantify the immunofluorescence of radiation-induced foci. The size of radiation-induced foci increased for both proteins over a 2-h period after nitrogen-ion irradiation, while the size of radiation-induced foci did not change after exposure to low-LET radiation. The number of radiation-induced ATMp foci showed a more rapid rise and greater frequency after X-ray exposure and was resolved more rapidly such that the frequency of radiation-induced foci decreased by 90 percent compared to 60 percent after exposure to high-LET radiation 2 h after 30 cGy. In contrast, the kinetics of radiation-induced gamma-H2AX focus formation was similar for high- and low-LET radiation in that it reached a plateau early and remained constant for up to 2 h. High-resolution 3D images of radiation-induced gamma-H2AX foci and dosimetry computation suggest that multiple double-strand breaks from nitrogen ions are encompassed within large nuclear domains of 4.4 Mbp. Our work shows that the size and frequency of radiation-induced foci vary as a function of radiation quality, dose, time and protein target. Thus, even though double-strand breaks and radiation-induced foci are correlated, the dynamic nature of both contradicts their accepted equivalence for low doses of different radiation qualities

  19. MRI appearance of radiation-induced changes of normal cervical tissues

    International Nuclear Information System (INIS)

    Noemayr, A.; Lell, M.; Bautz, W.; Sweeney, R.; Lukas, P.

    2001-01-01

    Irradiation causes specific MRI changes in anatomic morphology and signal intensity. To avoid misinterpretation, it is important to consider the potential radiation changes of normal tissue in MRI. The aim of this study was to describe the detected radiation effects on normal cervical tissues in MRI. Pretreatment and posttreatment MRI of 52 patients with primary neck tumors were evaluated retrospectively. The MR imaging was performed before initiating radiotherapy and at the end of the treatment period. Patients underwent follow-up studies within 24 months after the end of irradiation. Edema was the main radiation-induced effect. It was detected in the epiglottis, larynx, pharynx wall, retro- and parapharyngeal space, salivary glands, muscles, and subcutaneous tissue. In some cases the bone marrow of the mandible showed edema, due to osteonecrosis. We additionally detected fluid accumulation in the mastoid cells. Radiation caused volume reduction of the parotid gland, thickening of the pharynx wall, and fatty degeneration of bone marrow. Magnetic resonance imaging is an excellent method of depicting radiation-induced changes of normal tissue. Especially T2-weighted sequences allow the detection of even slight edema. It is important to be aware of the most common radiation-induced changes in MRI and to take them into account when assessing an examination. (orig.)

  20. 3D ultrasound Nakagami imaging for radiation-induced vaginal fibrosis

    Science.gov (United States)

    Yang, Xiaofeng; Rossi, Peter; Shelton, Joseph; Bruner, Debrorah; Tridandapani, Srini; Liu, Tian

    2014-03-01

    Radiation-induced vaginal fibrosis is a debilitating side-effect affecting up to 80% of women receiving radiotherapy for their gynecological (GYN) malignancies. Despite the significant incidence and severity, little research has been conducted to identify the pathophysiologic changes of vaginal toxicity. In a previous study, we have demonstrated that ultrasound Nakagami shape and PDF parameters can be used to quantify radiation-induced vaginal toxicity. These Nakagami parameters are derived from the statistics of ultrasound backscattered signals to capture the physical properties (e.g., arrangement and distribution) of the biological tissues. In this paper, we propose to expand this Nakagami imaging concept from 2D to 3D to fully characterize radiation-induced changes to the vaginal wall within the radiation treatment field. A pilot study with 5 post-radiotherapy GYN patients was conducted using a clinical ultrasound scanner (6 MHz) with a mechanical stepper. A serial of 2D ultrasound images, with radio-frequency (RF) signals, were acquired at 1 mm step size. The 2D Nakagami shape and PDF parameters were calculated from the RF signal envelope with a sliding window, and then 3D Nakagami parameter images were generated from the parallel 2D images. This imaging method may be useful as we try to monitor radiation-induced vaginal injury, and address vaginal toxicities and sexual dysfunction in women after radiotherapy for GYN malignancies.

  1. Radiation-induced loss of unsaturation in 1,2-polybutadiene

    International Nuclear Information System (INIS)

    Golub, M.A.; Cormia, R.D.

    1982-01-01

    The radiation induced loss of unsaturation and methyl production in 1,2-polybutadiene (VB) was studied using IR spectroscopy. It was found that G(-1,2), which depends on the initial vinyl content, decreased from approximately 550 for VB with 98.5% 1,2 initially, to approximately 270 for VB with 85% 1,2 initially. G(-trans-1,4) ranged from approximately 21 for VB with 14% trans-1,4 to nearly zero for VB with less than 1% trans-1,4 initially. Methyl production was found to equal one methyl group formed for every 4-5 vinyl units consumed in the radiation-cyclized VB, in contrast to one methyl formed for every two vinyls reacted during cationic cyclization to give monocyclic structures. The IR spectra of gamma-irradiated VB were very similar to the spectra of UV-irradiated or thermally-treated VB at the same residual vinyl contents. It is suggested that the radiation-induced cyclization of VB occurs by a nonionic, nonradical 'energy chain' mechanism, which apparently holds for the cyclization of VB, whether induced by gamma-rays, UV radiation, or heat

  2. Radiation induced structural changes in alpha-copper-zinc alloys

    International Nuclear Information System (INIS)

    Schuele, W.; Gieb, M.

    1991-01-01

    During irradiation of alpha-copper-zinc alloys with high energy electrons and protons a decrease of the electrical resistivity due to an increase of the degree of short range order is observed through radiation enhanced diffusion followed by an increase of the electrical resistivity through the formation of radiation induced interstitial clusters. The initial formation rate of interstitial clusters increases about linearly with the displacement rate for electron and proton irradiation. The largest initial formation rate is found between 60 and 130 0 C becoming negligibly small above 158 0 C and decreases drastically below 60 0 C. The dynamic steady state interstitial cluster concentration increases with decreasing irradiation temperature in the investigated temperature range between 158 and 40 0 C. Above 158 0 C the formation rate of interstitial clusters is negligibly small. Thus the transition temperature for radiation induced interstitial cluster formation is 158 0 C, depending mainly on the migration activation energy of vacancies. The radiation induced interstitial clusters are precipitates in those alloys in which the diffusion rate of the undersized component atoms via an interstitialcy diffusion mechanism is larger than that of the other atoms

  3. Study of radiation induced structural changes in nitrile rubber

    International Nuclear Information System (INIS)

    Cardona, F.; Hill, D.J.T.; Pomery, P.J.; Whittaker, A.K.

    1996-01-01

    Full text: Copolymers of butadiene (BD) and acrylonitrile (AN) (NBR rubber), have become important commercial material. NBR rubbers are part of a larger classification of products often referred to as special-purpose rubbers. Oil resistance is the most important property of nitrile rubbers, and refer to the ability of the vulcanised product to retain its original physical properties such as modulus, tensile strength, abrasion resistance and dimensions, while in contact with oils and fuels. Despite these reported advantages very few studies have been conducted on the radiation yields and structural changes in nitrile rubbers during exposure to high energy radiation. In this study we are investigating the stability against gamma and UV radiation, to different doses in vacuum, of butadiene, acrylonitrile and NBR copolymers with different composition ratio BD/AN. The mechanism of radiation induced structural changes is being investigated using experimental techniques such as ESR, NMR (Solid-state), FT-IR, RAMAN and UV spectroscopy. Also is being investigated the effect of irradiation on the mechanical properties of stressed and unstressed samples by TGA, DSC, DMA, Instron and Creep Test measurements. So far the main effect have been a marked radiation-induced loss of unsaturation in the butadiene units, cis to trans isomerization and formation of crosslink structures (intermolecular and intramolecular). One of the main challenges in the studies of NBR polymers is to observe directly the crosslinks produces by the radiation induced chemical reactions. IR spectroscopy is unsuitable because of the low molar absorbity of the peaks related to intermolecular crosslinking and the overlapping of the peaks (1630-1670 cm-1) related to intramolecular crosslinking (cyclization), with conjugated and nonconjugated (-C=C-; -C=N-) double bonds. A. K. Whittaker has shown that crosslink structures in PBD can be detected and measured directly using solid-state 13 C NMR. This technique

  4. Susceptibility to radiation-induced mammary carcinoma in genetically resistant Copenhagen rats

    International Nuclear Information System (INIS)

    Kamiya, Kenji; Nitta, Yumiko; Gould, M.N.

    2000-01-01

    The objective of this experiment was to compare the cellular basis of mammary cancer induction by a chemical carcinogen with induction by ionizing radiation in three strains of rats (inbred that have different genetic susceptibilities: COP rats, F344 rats, and WF rats). Rats were given a single intraperitoneal injection of 50 mg MNU/kg body weight as a mammary-tumor-inducing chemical carcinogen and were irradiated with a 3.0 Gy dose of 60 Co gamma rays at a dose rate of 26.58±1.19 cGy/min. The rats were inspected weekly, and they were killed and necropsied whenever palpable tumors were detected or they became moribund. The histopathological and immunohistochemical characteristics of the mammary tumors were investigated. A transplantation experiment using selected primary mammary tumors that developed in COP rats exposed to gamma rays was also performed to investigate the transplantability of mammary tumors induced by ionizing radiation. The sensitivity of the WF and F344 rats and the resistance of the COP rats to mammary carcinoma induction by the chemical carcinogen MNU was confirmed. In contrast to the chemical carcinogens, no difference in susceptibility to radiation induction of mammary carcinomas was detected among the three strains of rats, and immunohistochemical examination indicated that the radiation-induced carcinomas consisted of more highly differentiated cells than the MNU-induced cancers. The results of the experiment appear to support the hypothesis that differentiated mammary gland tissue is more resistant to chemical carcinogens than to cancer induction by radiation. The authors conclude that radiation-induced cancers in rats may develop via different pathways or from different cell populations than chemically induced cancers. (K.H.)

  5. Susceptibility to radiation-induced mammary carcinoma in genetically resistant Copenhagen rats

    Energy Technology Data Exchange (ETDEWEB)

    Kamiya, Kenji; Nitta, Yumiko [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine; Gould, M.N.

    2000-07-01

    The objective of this experiment was to compare the cellular basis of mammary cancer induction by a chemical carcinogen with induction by ionizing radiation in three strains of rats (inbred that have different genetic susceptibilities: COP rats, F344 rats, and WF rats). Rats were given a single intraperitoneal injection of 50 mg MNU/kg body weight as a mammary-tumor-inducing chemical carcinogen and were irradiated with a 3.0 Gy dose of {sup 60} Co gamma rays at a dose rate of 26.58{+-}1.19 cGy/min. The rats were inspected weekly, and they were killed and necropsied whenever palpable tumors were detected or they became moribund. The histopathological and immunohistochemical characteristics of the mammary tumors were investigated. A transplantation experiment using selected primary mammary tumors that developed in COP rats exposed to gamma rays was also performed to investigate the transplantability of mammary tumors induced by ionizing radiation. The sensitivity of the WF and F344 rats and the resistance of the COP rats to mammary carcinoma induction by the chemical carcinogen MNU was confirmed. In contrast to the chemical carcinogens, no difference in susceptibility to radiation induction of mammary carcinomas was detected among the three strains of rats, and immunohistochemical examination indicated that the radiation-induced carcinomas consisted of more highly differentiated cells than the MNU-induced cancers. The results of the experiment appear to support the hypothesis that differentiated mammary gland tissue is more resistant to chemical carcinogens than to cancer induction by radiation. The authors conclude that radiation-induced cancers in rats may develop via different pathways or from different cell populations than chemically induced cancers. (K.H.)

  6. Radiation-Induced Breast Cancer Incidence and Mortality From Digital Mammography Screening: A Modeling Study.

    Science.gov (United States)

    Miglioretti, Diana L; Lange, Jane; van den Broek, Jeroen J; Lee, Christoph I; van Ravesteyn, Nicolien T; Ritley, Dominique; Kerlikowske, Karla; Fenton, Joshua J; Melnikow, Joy; de Koning, Harry J; Hubbard, Rebecca A

    2016-02-16

    Estimates of risk for radiation-induced breast cancer from mammography screening have not considered variation in dose exposure or diagnostic work-up after abnormal screening results. To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening while considering exposure from screening and diagnostic mammography and dose variation among women. 2 simulation-modeling approaches. U.S. population. Women aged 40 to 74 years. Annual or biennial digital mammography screening from age 40, 45, or 50 years until age 74 years. Lifetime breast cancer deaths averted (benefits) and radiation-induced breast cancer incidence and mortality (harms) per 100,000 women screened. Annual screening of 100,000 women aged 40 to 74 years was projected to induce 125 breast cancer cases (95% CI, 88 to 178) leading to 16 deaths (CI, 11 to 23), relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95th percentile were projected to develop 246 cases of radiation-induced breast cancer leading to 32 deaths per 100,000 women. Women with large breasts requiring extra views for complete examination (8% of population) were projected to have greater radiation-induced breast cancer risk (266 cancer cases and 35 deaths per 100,000 women) than other women (113 cancer cases and 15 deaths per 100,000 women). Biennial screening starting at age 50 years reduced risk for radiation-induced cancer 5-fold. Life-years lost from radiation-induced breast cancer could not be estimated. Radiation-induced breast cancer incidence and mortality from digital mammography screening are affected by dose variability from screening, resultant diagnostic work-up, initiation age, and screening frequency. Women with large breasts may have a greater risk for radiation-induced breast cancer. Agency for Healthcare Research and Quality, U.S. Preventive Services Task Force, National Cancer Institute.

  7. Molecular analysis of radiation-induced experimental tumors in mice

    International Nuclear Information System (INIS)

    Niwa, O.; Muto, M.; Suzuki, F.

    1992-01-01

    Molecular analysis was made on mouse tumors induced by radiation and chemicals. Expression of oncogenes was studied in 12 types of 178 mouse tumors. Southern blotting was done on tumors in which overexpression of oncogenes was noted. Amplification of the myc oncogene was found in chemically induced sarcomas, but not those induced by radiations. Radiogenic thymomas were studied in detail. These thymomas were induced in two different ways. The first was thymomas induced by direct irradiation of F1 mice between C57BL/6NxC3H/He. Southern analysis of DNA revealed deletion of specific minisatellite bands in these tumors. DNA from directly induced thymomas induced focus formation when transfected into normal Golden hamster cells. The mouse K-ras oncogene was detected in these transformants. The second type of thymomas was induced by X-irradiation of thymectomized B10.thy1.2 mice in which normal thymus from congenic B10,thy1.1. mice was grafted. Thymomas of the donor origin was analysed by transfection and the transformants by DNA from those indirectly induced thymomas did not contain activated ras oncogenes. (author)

  8. Hypofractionated stereotactic radiotherapy to the rat hippocampus. Determination of dose response and tolerance

    International Nuclear Information System (INIS)

    Ernst-Stecken, A.; Roedel, F.; Grabenbauer, G.; Sauer, R.; Jeske, I.; Bluemcke, I.; Hess, A.; Ganslandt, O.; Brune, K.

    2007-01-01

    Purpose: To determine the effect of hypofractionated stereotactic radiotherapy (hfSRT) on adult rat brain tissue (necrosis, impact on blood-brain barrier, signal changes on high-field magnetic resonance imaging [MRI]). Material and Methods: Adult male Wistar rats underwent MRI and CT scanning of the brain and respective images were introduced into the Novalis trademark radiosurgery device (BrainLab, Feldkirchen, Germany). All animals (body weight 350 g) were irradiated weekly with doses of 2 x 10 Gy (n = 3 animals), 3 x 10 Gy (n = 3 animals) and 4 x 10 Gy (n = 3 animals), targeted to the left hippocampus after image-guided positioning. 4.7-T T2-weighted MRI scanning was performed in each animal. Animals were sacrificed 8, 12, and 16 weeks after hfSRT and brains were immersion-fixed in 4% paraformaldehyde for subsequent histopathologic analysis. Results: In concordance with isodose distributions, pathologic signal hyperintensities in MRI were recorded from 4 x 10 Gy after 8 weeks, 3 x 10 Gy after 12 weeks, while 2 x 10 Gy induced slight detectable alterations only after 16 weeks. Subsequent histopathologic analysis revealed hippocampal cell necrosis with significantly earlier and stronger occurrence for higher doses (40 Gy > 30 Gy > 20 Gy). Pial microvessel permeability also increased after 40 Gy, whereas 30 Gy induced moderate changes. Conclusion: Conclusion: Partial-brain irradiation with hfSRT (Novalis trademark System) was successfully adopted for small animals and histopathologic analysis confirmed its repositioning accuracy. The neuropathologic effects correlated with dose and observation time. The approach will be further developed for quality assurance in hfSRT of normal brain tissue, as well as novel treatment modalities in epileptic rats and orthotopic tumor models. (orig.)

  9. Perspectives in the paradigm of radiation-induced carcinogenesis

    International Nuclear Information System (INIS)

    Sugakhara, T.; Vatanabe, M.; Niva, O.; Nikajdo, O.

    1995-01-01

    Carcinogenesis is analysed as a multistage process consisting of initiation, promotion and progression. This model includes the mutation of oncogenes and the loss of hetrezygosity by tumor-suppressor genes. The threshold concept of radiation cancerogenesis is proposed, under which ionizing radiation can induce in somatic cell genetic effects a s result of DNA damage and epigenetic changes as well. The epigenetic changes (through DNA or cytoplasma) can be stabilized as mutations observed in many cancer cells and play a dominant role in radiation cancerogenesis induction. The ration of epigenetic and genetic effects largely depends on radiation doses

  10. Stimulation of respiration in rat thymocytes induced by ionizing radiation

    International Nuclear Information System (INIS)

    Gudz, T.I.; Pandelova, I.G.; Novgorodov, S.A.

    1994-01-01

    The effect of X irradiation on the respiration of rat thymocytes was studied. An increase in the rate of O 2 uptake was observed 1 h after cells were irradiated with doses of 6-10 Gy. The radiation-induced increase in respiration could be blocked by oligomycin, an inhibitor of mitochondrial ATP synthase, suggesting control by increased cytoplasmic ATP turnover. The stimulation of respiration was not associated with changes in the activity of mitochondrial electron transfer enzymes or permeability of the inner membrane. Several inhibitors of processes which used ATP were screened for their effects on the basal respiration rate and on the radiation response. In irradiated thymocytes, an enhancement of inhibition of respiration by ouabain, La 3+ and cycloheximide was observed. These results indicate that the radiation-induced stimulation of respiration is due to changes in ion homeostasis and protein synthesis. The effect of X irradiation was shown to be independent of the redox status of nonprotein thiols and was not associated with detectable changes in some products of lipid peroxidation. The radiation-induced decrease in activity of superoxide dismutase suggests free radical involvement in deleterious effects of radiation. 43 refs., 2 figs., 3 tabs

  11. Physiological bases and treatment to the radiation-induced emetic reflex

    International Nuclear Information System (INIS)

    Mulen Napoles, Barbara M.; Torres Babie, Priscilla; Ropero Toirac, Ramon de J.

    2002-01-01

    In the course of the specific oncologic treatment, there are frequent complications such as nausea and vomiting. The radiation-induced emetic reflex depends on various factors: primary site of radiation, administered dose, fractioning, irradiated volume, the sensory and psychic characteristics of the patient as well as the chemotherapy association. It is known that the afferent path to the so-called center of vomiting is determined by chemical mediators, protuberance receptors of the intracranial pressure and the unleashing chemoreceptor zone. In radiation-induced emesis, the exact mechanism is yet to be determined but it is known that radiation stimulates the production of chemical mediators and serotonin released by enterochromaffin cells that act upon the center of vomiting and vagal nucleus. Most of patients who are exposed to irradiation of their upper and middle hemibody as well as all the patients exposed to whole-body irradiation present with nausea and vomiting. The therapeutical anti-emetic recommendations are based on the neurochemical control of vomiting and the emetogenic effect of radiotherapy. 5HT3 receptor-antagonists are evaluated as effective agents in the control of radiation-induced emesis

  12. The process and promotion of radiation-induced cell death

    International Nuclear Information System (INIS)

    Sasaki, Hiroshi

    1998-01-01

    Radiation-induced cell death is divided into reproductive and interphase death, whose process can be revealed by time-lapse observations. Pedigree analyses of progenies derived from a surviving progenitor cell have shown that moribund cells appear in clusters among cells which are apparently undamaged (lethal sectoring). Sister cell fusion, which likely results from chromosome bridge, is the most frequently observed cell abnormality leading to reproductive death. While interphase death does not occur unless the dose exceeds 10 Gy for low LET radiation such as X-rays, high-LET radiation is very effective at inducing interphase death (RBE: ≅3 at 230 keV/μm). Expression or fixation of potentially lethal damage (PLD) is closely associated with cell cycle events and enhanced by inducing premature chromosome condensation (PCC) at a nonpermissive temperature in tsBN2 cells with a ts-defect in RCC1 protein (a regulator of chromatin condensation) which monitors the completion of DNA replication. Furthermore, higher-order structural changes in nuclear matrix such as induced by leptomycin B, an inhibitor of CRM1 (chromosome region maintenance) protein, also play an important role in the fixation of PLD. (author)

  13. SU-F-J-124: Reduction in Dosimetric Impact of Motion Using VMAT Compared to IMRT in Hypofractionated Prostate Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ravindranath, B; Xiong, J; Happersett, L; Mageras, G; Zhang, P; Hunt, M [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

    2016-06-15

    Purpose: To quantify and compare the dosimetric impact of motion management correction strategies during VMAT and IMRT for hypofractionated prostate treatment. Methods: Two arc VMAT and 9 field IMRT plans were generated for two prostate cancer patients undergoing hypofractionated radiotherapy (7.5Gy × 5 and 8Gy × 5). 212 motion traces were retrospectively extracted from treatment records of prostate cancer patients with implanted Calypso beacons. Dose to the CTV and normal tissues was reconstructed for each trace and plan taking into account the actual treatment delivery time. Following motion correction scenarios were simulated: (1) VMAT plan – (a) No correction, (b) correction between arcs, (c) correction every 20 degrees of gantry rotation and (2) IMRT plan - (a) No correction,(b) correction between fields. Two mm action threshold for position correction was assumed. The 5–95% confidence interval (CI) range was extracted from the family of DVHs for each correction scenario. Results: Treatment duration for 8Gy plan (VMAT vs IMRT) was 3 vs 12 mins and for 7.5Gy plan was 3 vs 9 mins. In the absence of correction, the VMAT 5–−95% CI dose spread was, on average, less than the IMRT dose spread by 2% for CTVD95, 9% for rectalwall (RW) D1cc and 9% for bladderwall (BW) D53. Further, VMAT b/w arcs correction strategy reduced the spread about the planned value compared to IMRT b/w fields correction by: 1% for CTVD95, 2.6% for RW1cc and 2% for BWD53. VMAT 20 degree strategy led to greater reduction in dose spread compared to IMRT by: 2% for CTVD95, 4.5% for RW1cc and 6.7% for BWD53. Conclusion: In the absence of a correction strategy, the limited motion during VMAT’s shorter delivery times translates into less motion-induced dosimetric degradation than IMRT. Performing limited periodic motion correction during VMAT can yield excellent conformity to planned values that is superior to IMRT. This work was partially supported by Varian Medical Systems.

  14. A juvenile case of radiation-induced meningioma two years after radiation for craniopharyngioma

    International Nuclear Information System (INIS)

    Kano, Tomoaki; Zama, Akira; Ono, Nobuo; Nakamura, Tadashi; Tamura, Masaru; Ohe, Tihiro; Nakazato, Yoichi

    1994-01-01

    The patient was a 7-years-old boy who received radiation therapy of 50 Gy after total gross removal of a craniopharyngioma. After two years a follow up CT scan showed a new enhanced lesion in the right temporal tip within the previous irradiation field. Total removal of the tumor was performed and its histological examination showed it to be an atypical meningioma. This atypical meningioma satisfied Cahan's criteria. So we diagnosed this atypical meningioma as radiation-induced meningioma. Immunohistochemically this meningioma stained for Vimentin. An electron microscopical examination showed neither desmosome nor interdigitation. The score of Ki-67 and BrdU-L. I was very small. Compared with previously reported juvenile radiation-induced meningioma, the latency was very short. The patient received growth hormone (GH) replacement therapy. We suspected relation between GH replacement therapy and short latency. He was discharged without any new neurological deficits and we haven't detected tumor recurrence for two years. (author)

  15. A juvenile case of radiation-induced meningioma two years after radiation for craniopharyngioma

    Energy Technology Data Exchange (ETDEWEB)

    Kano, Tomoaki; Zama, Akira; Ono, Nobuo; Nakamura, Tadashi; Tamura, Masaru; Ohe, Tihiro; Nakazato, Yoichi (Gunma Univ., Maebashi (Japan). School of Medicine)

    1994-04-01

    The patient was a 7-years-old boy who received radiation therapy of 50 Gy after total gross removal of a craniopharyngioma. After two years a follow up CT scan showed a new enhanced lesion in the right temporal tip within the previous irradiation field. Total removal of the tumor was performed and its histological examination showed it to be an atypical meningioma. This atypical meningioma satisfied Cahan's criteria. So we diagnosed this atypical meningioma as radiation-induced meningioma. Immunohistochemically this meningioma stained for Vimentin. An electron microscopical examination showed neither desmosome nor interdigitation. The score of Ki-67 and BrdU-L. I was very small. Compared with previously reported juvenile radiation-induced meningioma, the latency was very short. The patient received growth hormone (GH) replacement therapy. We suspected relation between GH replacement therapy and short latency. He was discharged without any new neurological deficits and we haven't detected tumor recurrence for two years. (author).

  16. Treatment of Radiation Induced Biological Changes by Bone Marrow Transplantation

    International Nuclear Information System (INIS)

    El-Missiry, M.A.; Shehata, G.; Roushdy, H.M; Fayed, Th.A.

    1999-01-01

    Preventing the propagation of radiation induced oxidative damage has been a subject of considerable investigations. The ultimate goal of the present study is to use bone marrow cells to ameliorate or to treat the radiation sickness. Transplantation of bone marrow cell has shown promising results in the present experimental radiation treatment. In this report, suspension of bone marrow cells was injected into rats 12 h. after exposure to 4.5 Gy whole body gamma irradiation. Significant results were recorded on the successful control of the radiation induced disorders in a number of biochemical parameters including certain enzymatic and nonenzymatic antioxidants (superoxide dismutase and glutathione) and certain parameters related to kidney function including creatinine, urea as well as Atpase Activity in blood serum, urine and kidney tissue

  17. Caffeine Markedly Enhanced Radiation-Induced Bystander Effects

    International Nuclear Information System (INIS)

    Jiang Erkang; Wu Lijun

    2009-01-01

    In this paper it is shown that incubation with 2 mM caffeine enhanced significantly the MN (micronucleus) formation in both the 1 cGy α-particle irradiated and non-irradiated bystander regions. Moreover, caffeine treatment made the non-irradiated bystander cells more sensitive to damage signals. Treated by c-PTIO(2-(4-carboxy-phenyl)- 4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide), a nitric oxide (NO) scavenger, the MN frequencies were effectively inhibited, showing that nitric oxide might be very important in mediating the enhanced damage. These results indicated that caffeine enhanced the low dose α-particle radiation-induced damage in irradiated and non-irradiated bystander regions, and therefore it is important to investigate the relationship between the radiosensitizer and radiation-induced bystander effects (RIBE). (ion beam bioengineering)

  18. Non-radiation induced signals in TL dosimetry

    International Nuclear Information System (INIS)

    German, U.; Weinstein, M.

    2002-01-01

    One source of background signals, which are non-radiation related, is the reader system and it includes dark current, external contaminants and electronic spikes. These factors can induce signals equivalent to several hundredths of mSv. Mostly, the effects are minimised by proper design of the TLD reader, but some effects are dependent on proper operation of the system. The other main group of background signals originate in the TL crystal and is due to tribothermoluminescence, dirt, chemical reactions and stimulation by visible or UV light. These factors can have a significant contribution, equivalent to over several mSv, depending on whether the crystal is bare or protected by PTFE. Working in clean environments, monitoring continuously the glow curve and performing glow curve deconvolution are suggested to minimise non-radiation induced spurious signals. (author)

  19. Radiation-induced transmission spectral variations of Ce3+-doped heavy germanate glasses

    International Nuclear Information System (INIS)

    Yang Yunxia; Baccaro, S.; Cecilia, A.; Rao Jinhua; Zhang Junbiao; Xia Fang; Chen Guorong

    2005-01-01

    Radiation-induced transmission spectral variations of Ce 3+ -doped heavy germanate glasses used as scintillating materials are presented. Glass matrix contains mainly GeO 2 , BaO and Gd 2 O 3 with a density higher than 5 g/cm 3 . Glasses are melted in the different atmosphere. The transmission spectra of glasses before and after radiation treatments are measured and compared. Unlike exhibiting the monotonous deterioration effect on the glass matrix, radiation plays the radiation protection role, even making enhanced transmission of Ce 3+ -doped glasses, depending upon glass melting atmosphere and radiation dose. Radiation-induced reducing and oxidizing mechanism is proposed to explain phenomena

  20. Binding of radiation-induced phenylalanine radicals to DNA

    International Nuclear Information System (INIS)

    Schans, G.P. van der; Rijn, C.J.S. van; Bleichrodt, J.F.

    1975-11-01

    When an aqueous solution of double-stranded DNA of bacteriophage PM2 containing phenylalanine and saturated with N 2 O is irradiated with γ-rays, radiation-induced phenylalanine radicals are bound covalently. Under the conditions used about 25 phenylalanine molecules may be bound per lethal hit. Also for single-stranded PM2 DNA, most of the phenylalanine radicals bound are non-lethal. Evidence is presented that in double-stranded DNA an appreciable fraction of the single-strand breaks is induced by phenylalanine radicals. Radiation products of phenylalanine and the phenylalanine bound to the DNA decrease the sensitivity of the DNA to the induction of single-strand breaks. There are indications that the high efficiency of protection by radiation products of phenylalanine is due to their positive charge, which will result in a relatively high concentration of these compounds in the vicinity of the negatively charged DNA molecules

  1. Investigation of radiation-induced multilayered signalling response of the inflammatory pathway

    International Nuclear Information System (INIS)

    Babini, G.; Ugolini, M.; Morini, J.; Baiocco, G.; Ottolenghi, A.; Mariotti, L.; Tabarelli de Fatis, P.; Liotta, M.

    2015-01-01

    Ionising radiation exposure of cells might induce the perturbation of cell functions and, in particular, the activation or inhibition of several important pathways. This perturbation can cause the deregulation of both intra- and extra-cellular signalling cascades (such as the inflammatory pathway) and alter not only the behaviour of directly exposed cells but also the neighbouring nonirradiated ones, through the so-called bystander effect. The aim of the present work was to investigate the complex nonlinear interactions between the inflammatory pathway and other strictly interlaced signalling pathways, such as Erk1/2 and Akt/PKB, focusing on the radiation-induced perturbation of such pathways in the dose range of 0 -2 Gy. The results show how radiation affects these interconnected pathways and how confounding factors, such as the change of culture medium, can hide radiation-induced perturbations. (authors)

  2. Influence of radiation-induced apoptosis on development brain in molecular regulation

    International Nuclear Information System (INIS)

    Gu Guixiong

    2000-01-01

    An outline of current status on the influence of radiation on the development brain was given. Some genes as immediate early gene, Bcl-2 family, p53, heat shock protein and AT gene play an important regulation role in ionizing radiation-induced development brain cells apoptosis. And such biological factor as nerve growth factor, interleukin-1, tumor necrosis factor, basic fibroblast growth factor, transforming growth factor and so on have a vital protection function against ionizing radiation-induced cells apoptosis

  3. Radiation-induced reactions in polydimethyl siloxanes

    International Nuclear Information System (INIS)

    Menhofer, H.

    1988-01-01

    The dissertation reports an investigation into the behaviour of polydimethyl soloxanes (PDMS) subject to the radiation field of a 60 Co-γ radiation source at different irradiation conditions. Several different analytical methods have been applied for the detection of chemical changes in the material and their effects on the polymeric segment mobility. Application of the ESR-spintrap technique identifies the primary radicals x CH 3 , -Si x , and -Si-CH 2 x , induced by the radiolysis of the PDMS. The individual rates of radical formation have been found to be strongly dependent on temperature. (orig./LU) [de

  4. Injection profiles with radiation induced copolymers

    International Nuclear Information System (INIS)

    Knight, B.L.; Rhudy, J.S.; Gogarty, W.B.

    1976-01-01

    The injectivity profile of a heterogeneous formation and/or vertical conformance is improved by injecting an aqueous solution into the formation, the solution containing a polymer obtained as a product of radiation-induced polymerization of acrylamide and/or methacrylamide and acrylic acid, methacrylic acid, and/or alkali metal salts thereof. The polymerization is preferably carried out in a 10 to 60 percent aqueous solution with gamma radiation; the aqueous monomer solution preferably contains 25 to 99 percent acrylamide and 1 to 75 percent sodium acrylate. Immiscible, miscible, or miscible-like displacing processes can be used in conjunction with this invention. 20 claims

  5. Radiation-induced mutations in mammals

    International Nuclear Information System (INIS)

    Ehling, U.H.

    1993-01-01

    The aims of the proposed project are to provide a better basis for extrapolation of animal data to man. Genetic endpoint, strain and species comparisons are made, which will provide critical experimental data regarding strategies in extrapolating laboratory animal data to man. Experiments were conducted to systematically compare the spontaneous and radiation-induced mutation rates for recessive specific-locus, dominant cataract and enzyme activity alleles in the mouse as well as a comparison of the mutation rate in the mouse and hamster for dominant cataract and enzyme activity alleles. The comparison of the radiation-dose response for recessive specific-locus and dominant cataract mutations are extended. Selected mutations are characterized at the genetic, biochemical and molecular levels. (R.P.) 5 refs., 3 tabs

  6. Thioredoxin mitigates radiation-induced hematopoietic stem cell injury in mice

    Directory of Open Access Journals (Sweden)

    Pasupathi Sundaramoorthy

    2017-11-01

    Full Text Available Abstract Background Radiation exposure poses a significant threat to public health. Hematopoietic injury is one of the major manifestations of acute radiation sickness. Protection and/or mitigation of hematopoietic stem cells (HSCs from radiation injury is an important goal in the development of medical countermeasure agents (MCM. We recently identified thioredoxin (TXN as a novel molecule that has marked protective and proliferative effects on HSCs. In the current study, we investigated the effectiveness of TXN in rescuing mice from a lethal dose of total body radiation (TBI and in enhancing hematopoietic reconstitution following a lethal dose of irradiation. Methods We used in-vivo and in-vitro methods to understand the biological and molecular mechanisms of TXN on radiation mitigation. BABL/c mice were used for the survival study and a flow cytometer was used to quantify the HSC population and cell senescence. A hematology analyzer was used for the peripheral blood cell count, including white blood cells (WBCs, red blood cells (RBCs, hemoglobin, and platelets. Colony forming unit (CFU assay was used to study the colongenic function of HSCs. Hematoxylin and eosin staining was used to determine the bone marrow cellularity. Senescence-associated β-galactosidase assay was used for cell senescence. Western blot analysis was used to evaluate the DNA damage and senescence protein expression. Immunofluorescence staining was used to measure the expression of γ-H2AX foci for DNA damage. Results We found that administration of TXN 24 h following irradiation significantly mitigates BALB/c mice from TBI-induced death: 70% of TXN-treated mice survived, whereas only 25% of saline-treated mice survived. TXN administration led to enhanced recovery of peripheral blood cell counts, bone marrow cellularity, and HSC population as measured by c-Kit+Sca-1+Lin– (KSL cells, SLAM + KSL cells and CFUs. TXN treatment reduced cell senescence and radiation-induced

  7. Search for the lowest irradiation dose from literatures on radiation-induced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yoshizawa, Y; Kusama, T [Tokyo Univ. (Japan). Faculty of Medicine

    1975-12-01

    A survey of past case reports concerning radiation-induced breast cancer was carried out in order to find the lowest irradiation dose. The search of literature published since 1951 revealed 10 cases of radiation-induced breast cancer. Only 5 cases had precise descriptions of the irradiation dose. The lowest irradiation dose was estimated at 1470 rads in the case of external X-ray irradiation for tuberous angioma. All of cases of radiation-induced breast cancer had received radiation for the treatment of nonmalignant tumors, such as pulmonary tuberculosis, mastitis, and tuberous angioma. There also were three statistical studies. The first concerned atomic bomb survivors, the second, pulmoanry tuberculous patients subjected to frequent fluoroscopies, and the third, patients of acute post partum mastitis. These statistical studies had revealed a significant increase in the incidence of breast cancer in the irradiated group, but there was little information about the lowest irradiation dose. It was noticed that radiation-induced breast cancer was more numerous in the upper inner quadrant of the breast. Most histopathological findings of radiation-induced breast cancer involved duct cell carcinoma. The latent period was about 15 years.

  8. Visual sensations induced by Cherenkov radiation

    International Nuclear Information System (INIS)

    McNulty, P.J.; Pease, V.P.; Bond, V.P.

    1975-01-01

    Pulses of relativistic singly charged particles entering the eyeball induce a variety of visual phenomena by means of Cerenkov radiation generated during their passage through the vitreous. These phenomena are similar in appearance to many of the visual sensations experienced by Apollo astronauts exposed to the cosmic rays in deep space

  9. Hypofractionated Prostate Radiotherapy with or without Conventionally Fractionated Nodal Irradiation: Clinical Toxicity Observations and Retrospective Daily Dosimetry.

    Science.gov (United States)

    McDonald, Andrew M; Bishop, Justin M; Jacob, Rojymon; Dobelbower, Michael C; Kim, Robert Y; Yang, Eddy S; Smith, Heather; Wu, Xingen; Fiveash, John B

    2012-01-01

    Purpose. To evaluate toxicity associated with the addition of elective nodal irradiation (ENI) to a hypofractionated regimen for the treatment of prostate cancer. Methods and Materials. Fifty-seven patients received pelvic image-guided IMRT to 50.4 Gy in 28 fractions with a hypofractionated simultaneous boost to the prostate to 70 Gy. Thirty-one patients received prostate-only treatment to 70 Gy in 28 fractions. Results. Median followup was 41.1 months. Early grade ≥2 urinary toxicity rates were 49% (28 of 57) for patients receiving ENI and 58% (18 of 31) for those not (P = 0.61). Early grade ≥2 rectal toxicity rates were 40% (23 of 57) and 23% (7 of 31), respectively (P = 0.09). The addition of ENI resulted in a 21% actuarial rate of late grade ≥2 rectal toxicity at 4 years, compared to 0% for patients treated to the prostate only (P = 0.02). Retrospective daily dosimetry of patients experiencing late rectal toxicity revealed an average increase of 2.67% of the rectal volume receiving 70 Gy compared to the original plan. Conclusions. The addition of ENI resulted in an increased risk of late rectal toxicity. Grade ≥2 late rectal toxicity was associated with worse daily rectal dosimetry compared to the treatment plan.

  10. Expanding the use of real‐time electromagnetic tracking in radiation oncology

    Science.gov (United States)

    Kupelian, Patrick A.; Willoughby, Twyla R.; Meeks, Sanford L.

    2011-01-01

    In the past 10 years, techniques to improve radiotherapy delivery, such as intensity‐modulated radiation therapy (IMRT), image‐guided radiation therapy (IGRT) for both inter‐ and intrafraction tumor localization, and hypofractionated delivery techniques such as stereotactic body radiation therapy (SBRT), have evolved tremendously. This review article focuses on only one part of that evolution, electromagnetic tracking in radiation therapy. Electromagnetic tracking is still a growing technology in radiation oncology and, as such, the clinical applications are limited, the expense is high, and the reimbursement is insufficient to cover these costs. At the same time, current experience with electromagnetic tracking applied to various clinical tumor sites indicates that the potential benefits of electromagnetic tracking could be significant for patients receiving radiation therapy. Daily use of these tracking systems is minimally invasive and delivers no additional ionizing radiation to the patient, and these systems can provide explicit tumor motion data. Although there are a number of technical and fiscal issues that need to be addressed, electromagnetic tracking systems are expected to play a continued role in improving the precision of radiation delivery. PACS number: 87.63.‐d PMID:22089017

  11. Challenges in Clinical Management of Radiation-Induced Illnesses in Exploration Spaceflight

    Science.gov (United States)

    Blue, Rebecca; Chancellor, Jeffery; Suresh, Rahul; Carnell, Lisa; Reyes, David; Nowadly, Craig; Antonsen, Erik

    2018-01-01

    Historical solar particle events (SPEs) provide context for some understanding of acute radiation exposure risk to astronauts traveling outside of low Earth orbit. Modeling of potential doses delivered to exploration crewmembers anticipates limited radiation-induced health impacts, including prodromal symptoms of nausea, emesis, and fatigue, but suggests that more severe clinical manifestations are unlikely. Recent large animal-model research in space-analogs closely mimicking SPEs has identified coagulopathic events independent of the hematopoietic sequelae of higher radiation doses, similar in manifestation to disseminated intravascular coagulation (DIC). We explored the challenges of clinical management of radiation-related clinical manifestations, using currently accepted modeling techniques and anticipated physiological sequelae, to identify medical capabilities needed to successfully manage SPE-induced radiation illnesses during exploration spaceflight.

  12. [Radiation-induced bystander effect: the important part of ionizing radiation response. Potential clinical implications].

    Science.gov (United States)

    Wideł, Maria; Przybyszewski, Waldemar; Rzeszowska-Wolny, Joanna

    2009-08-18

    It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the "bystander effect" or "radiation-induced bystander effect" (RIBE). This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy), but also after conventional irradiation (X-rays, gamma rays) at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not definitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effect may have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation field and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The bystander effect may be a

  13. Radiation-induced bystander effect: The important part of ionizing radiation response. Potential clinical implications

    Directory of Open Access Journals (Sweden)

    Maria Wideł

    2009-08-01

    Full Text Available It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the “bystander effect” or “radiation-induced bystander effect” (RIBE. This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy, but also after conventional irradiation (X-rays, gamma rays at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not defi nitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effectmay have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation fi eld and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The

  14. Radiation-induced optic neuropathy: A magnetic resonance imaging study

    International Nuclear Information System (INIS)

    Guy, J.; Mancuso, A.; Beck, R.; Moster, M.L.; Sedwick, L.A.; Quisling, R.G.; Rhoton, A.L. Jr.; Protzko, E.E.; Schiffman, J.

    1991-01-01

    Optic neuropathy induced by radiation is an infrequent cause of delayed visual loss that may at times be difficult to differentiate from compression of the visual pathways by recurrent neoplasm. The authors describe six patients with this disorder who experienced loss of vision 6 to 36 months after neurological surgery and radiation therapy. Of the six patients in the series, two had a pituitary adenoma and one each had a metastatic melanoma, multiple myeloma, craniopharyngioma, and lymphoepithelioma. Visual acuity in the affected eyes ranged from 20/25 to no light perception. Magnetic resonance (MR) imaging showed sellar and parasellar recurrence of both pituitary adenomas, but the intrinsic lesions of the optic nerves and optic chiasm induced by radiation were enhanced after gadolinium-diethylenetriaminepenta-acetic acid (DTPA) administration and were clearly distinguishable from the suprasellar compression of tumor. Repeated MR imaging showed spontaneous resolution of gadolinium-DTPA enhancement of the optic nerve in a patient who was initially suspected of harboring recurrence of a metastatic malignant melanoma as the cause of visual loss. The authors found the presumptive diagnosis of radiation-induced optic neuropathy facilitated by MR imaging with gadolinium-DTPA. This neuro-imaging procedure may help avert exploratory surgery in some patients with recurrent neoplasm in whom the etiology of visual loss is uncertain

  15. Factors that modify risks of radiation-induced cancer

    International Nuclear Information System (INIS)

    Fabrikant, J.I.

    1988-11-01

    The collective influence of biologic and physical factors that modify risks of radiation-induced cancer introduces uncertainties sufficient to deny precision of estimates of human cancer risk that can be calculated for low-dose radiation in exposed populations. The important biologic characteristics include the tissue sites and cell types, baseline cancer incidence, minimum latent period, time-to-tumor recognition, and the influence of individual host (age and sex) and competing etiologic influences. Physical factors include radiation dose, dose rate, and radiation quality. Statistical factors include time-response projection models, risk coefficients, and dose-response relationships. Other modifying factors include other carcinogens, and other biological sources (hormonal status, immune status, hereditary factors)

  16. Radiation-induced creep and swelling

    International Nuclear Information System (INIS)

    Heald, P.T.

    1977-01-01

    The physical basis for radiation induced creep and swelling is reviewed. The interactions between the point defects and dislocations are recalled since these interactions are ultimately responsible for the observable deformation phenomena. Both the size misfit interaction and the induced inhomogeneity interaction are considered since the former gives rise to irradiation swelling while the latter, which depends on both internal and external stresses, results in irradiation creep. The defect kinetics leading to the deformation processes are discussed in terms of chemical rate theory. The rate equations for the spatially averaged interstitial and vacancy concentrations are expressed in terms of the microstructural sink strengths and the solution of these equations leads to general expressions for the deformation rates

  17. Radiological-morphological synopsis of radiation-induced lung fibrosis

    International Nuclear Information System (INIS)

    Bublitz, G.

    1977-01-01

    As delayed radiation damage after treatment of bronchial carcinoma and mamma carcinoma, fibroses occur as a reaction of the tissues. They have become a clinical-functional syndrome because of their uniform clinicaL-radiological symptomatology and pathophysiology. Pulmonary fibrosis as delayed radiation damage has a special importance with its two different radiation effects on connective tissue: a) on existing structures, b) delayed alterations of the connective tissue. As seen from experiments on lungs of men and rats, radiation-induced alterations can be measured by testing the different solubilities of the collagen types. In addition to the pathologically disordered collagen production, 9 weeks after the irradiation the radiation fibrosis leads to an isolated increase of insoluble collagen corresponding to the formation of metabolism-resistant fibrils. (MG) [de

  18. Modulation of radiation-induced apoptosis and G2/M block in murine T-lymphoma cells

    International Nuclear Information System (INIS)

    Palayoor, S.T.; Macklis, R.M.; Bump, E.A.; Coleman, C.N.

    1995-01-01

    Radiation-induced apoptosis in lymphocyte-derived cell lines is characterized by endonucleolytic cleavage of cellular DNA within hours after radiation exposure. We have studied this phenomenon qualitatively (DNA gel electrophoresis) and quantitatively (diphenylamine reagent assay) in murine EL4 T-lymphoma cells exposed to 137 Cs γ irradiation. Fragmentation was discernible within 18-24 h after exposure. It increased with time and dose and reached a plateau after 8 Gy of γ radiation. We studied the effect of several pharmacological agents on the radiation-induced G 2 /M block and DNA fragmentation. The agents which reduced the radiation-induced G 2 /M-phase arrest (caffeine, theobromine, theophylline and 2-aminopurine) enhanced the degree of DNA fragmentation at 24 h. In contrast, the agents which sustained the radiation-induced G 2 /M-phase arrest (TPA, DBcAMP, IBMX and 3-aminobenzamide) inhibited the DNA fragmentation at 24 h. These studies on EL4 lymphoma cells are consistent with the hypothesis that cells with radiation-induced genetic damage are eliminated by apoptosis subsequent to a G 2 /M block. Furthermore, it may be possible to modulate the process of radiation-induced apoptosis in lymphoma cells with pharmacological agents that modify the radiation-induced G 2 /M block, and to use this effect in the treatment of patients with malignant disease. 59 refs., 7 figs

  19. Radiation-Induced Bystander Response: Mechanism and Clinical Implications

    Science.gov (United States)

    Suzuki, Keiji; Yamashita, Shunichi

    2014-01-01

    Significance: Absorption of energy from ionizing radiation (IR) to the genetic material in the cell gives rise to damage to DNA in a dose-dependent manner. There are two types of DNA damage; by a high dose (causing acute or deterministic effects) and by a low dose (related to chronic or stochastic effects), both of which induce different health effects. Among radiation effects, acute cutaneous radiation syndrome results from cell killing as a consequence of high-dose exposure. Recent advances: Recent advances in radiation biology and oncology have demonstrated that bystander effects, which are emerged in cells that have never been exposed, but neighboring irradiated cells, are also involved in radiation effects. Bystander effects are now recognized as an indispensable component of tissue response related to deleterious effects of IR. Critical issues: Evidence has indicated that nonapoptotic premature senescence is commonly observed in various tissues and organs. Senesced cells were found to secrete various proteins, including cytokines, chemokines, and growth factors, most of which are equivalent to those identified as bystander factors. Secreted factors could trigger cell proliferation, angiogenesis, cell migration, inflammatory response, etc., which provide a tissue microenvironment assisting tissue repair and remodeling. Future directions: Understandings of the mechanisms and physiological relevance of radiation-induced bystander effects are quite essential for the beneficial control of wound healing and care. Further studies should extend our knowledge of the mechanisms of bystander effects and mode of cell death in response to IR. PMID:24761341

  20. A novel topical protectant for the prevention of β-radiation induced moist desquamation

    International Nuclear Information System (INIS)

    Ma, L.; Wilcock, S.; Rezvani, M.; Hsia, C.

    2003-01-01

    Full text: Effective therapies for the prevention of radiation-induced skin burns that could be readily deployed under a nuclear accident or nuclear terrorism scenario are urgently needed. In this report we describe the efficacy of a novel radioprotectant (DMZ911) in a model of b-radiation induced moist desquamation (MD) in pig skin. DMZ911 is a nitroxide-based topical cream that effectively delivers the nitroxide into viable skin cells. Stable nitroxide compounds have been shown to be effective against both X-ray and ?-ray-induced damage in vivo and in vitro. A pig skin model of β-radiation-induced MD was employed in this study. Exposure to 30 Gy was used to induce skin lesions involving >80% moist desquamation in prescribed test sites on flank skin of female Large White pigs. DMZ911 or placebo was applied to various test sites 2 hours prior to radiation exposure. Lesions were scored based on the area of the test site containing 50% MD (severe) as determined by clinical assessment using blinded observers. Treatment with DMZ911 resulted in a 31% net reduction in MD when compared to placebo treated sites following an 8-week study period. This reduction was observed whether all sites or only those with severe MD were considered. Skin damage (as indicated by MD) from radiation exposure was significantly reduced by 31% (p = 0.05) following pretreatment with the novel topical radioprotectant DMZ911. This observation suggests that skin lesion development from radiation-induced oxidative damage cascades may be successfully inhibited by treatment with DMZ911. This topical therapeutic agent represents a novel treatment for nuclear radiation induced skin injury. DMZ911 may have unique applications in radiation oncology, cosmetic and therapeutic UV, laser, glycolic and dermabrasion procedures

  1. Caspase-independent cell death mediated by apoptosis-inducing factor (AIF) nuclear translocation is involved in ionizing radiation induced HepG2 cell death

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Hengwen [Department of Radiation, Cancer Center of Guangdong General Hospital (Guangdong Academy of Medical Science), Guangzhou, 510080, Guangdong (China); Yang, Shana; Li, Jianhua [Department of Physiology, Guangzhou Medical University, Guangzhou, 510182, Guangdong (China); Zhang, Yajie [Department of Pathology, Guangzhou Medical University, Guangzhou, 510182, Guangdong (China); Gao, Dongsheng [Department of Oncology, Guangdong Medical College Affiliated Pengpai Memorial Hospital, Hai Feng, 516400, Gungdong (China); Zhao, Shenting, E-mail: zhaoshenting@126.com [Department of Physiology, Guangzhou Medical University, Guangzhou, 510182, Guangdong (China)

    2016-03-25

    Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The aim of radiotherapy is to eradicate cancer cells with ionizing radiation. Except for the caspase-dependent mechanism, several lines of evidence demonstrated that caspase-independent mechanism is directly involved in the cell death responding to irradiation. For this reason, defining the contribution of caspase-independent molecular mechanisms represents the main goal in radiotherapy. In this study, we focused on the role of apoptosis-inducing factor (AIF), the caspase-independent molecular, in ionizing radiation induced hepatocellular carcinoma cell line (HepG2) cell death. We found that ionizing radiation has no function on AIF expression in HepG2 cells, but could induce AIF release from the mitochondria and translocate into nuclei. Inhibition of AIF could reduce ionizing radiation induced HepG2 cell death. These studies strongly support a direct relationship between AIF nuclear translocation and radiation induced cell death. What's more, AIF nuclear translocation is caspase-independent manner, but not caspase-dependent manner, in this process. These new findings add a further attractive point of investigation to better define the complex interplay between caspase-independent cell death and radiation therapy. - Highlights: • AIF nuclear translocation is involved in ionizing radiation induced hepatocellular carcinoma cell line HepG2 cell death. • AIF mediated cell death induced by ionizing radiation is caspase-independent. • Caspase-independent pathway is involved in ionzing radiation induced HepG2 cell death.

  2. Caspase-independent cell death mediated by apoptosis-inducing factor (AIF) nuclear translocation is involved in ionizing radiation induced HepG2 cell death

    International Nuclear Information System (INIS)

    Sun, Hengwen; Yang, Shana; Li, Jianhua; Zhang, Yajie; Gao, Dongsheng; Zhao, Shenting

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The aim of radiotherapy is to eradicate cancer cells with ionizing radiation. Except for the caspase-dependent mechanism, several lines of evidence demonstrated that caspase-independent mechanism is directly involved in the cell death responding to irradiation. For this reason, defining the contribution of caspase-independent molecular mechanisms represents the main goal in radiotherapy. In this study, we focused on the role of apoptosis-inducing factor (AIF), the caspase-independent molecular, in ionizing radiation induced hepatocellular carcinoma cell line (HepG2) cell death. We found that ionizing radiation has no function on AIF expression in HepG2 cells, but could induce AIF release from the mitochondria and translocate into nuclei. Inhibition of AIF could reduce ionizing radiation induced HepG2 cell death. These studies strongly support a direct relationship between AIF nuclear translocation and radiation induced cell death. What's more, AIF nuclear translocation is caspase-independent manner, but not caspase-dependent manner, in this process. These new findings add a further attractive point of investigation to better define the complex interplay between caspase-independent cell death and radiation therapy. - Highlights: • AIF nuclear translocation is involved in ionizing radiation induced hepatocellular carcinoma cell line HepG2 cell death. • AIF mediated cell death induced by ionizing radiation is caspase-independent. • Caspase-independent pathway is involved in ionzing radiation induced HepG2 cell death.

  3. Effects of phenobarbital on taste aversion induced by x-radiation

    International Nuclear Information System (INIS)

    Jolicoeur, F.B.; Wayner, M.J.; Rondeau, D.B.; Merkel, A.D.; Bassano, D.A.

    1979-01-01

    The effects of phenobarbital on taste aversion induced by x-radiation were examined. Rats were adapted to a 23 hr 50 min water deprivation schedule. On the Treatment Day animals were given a novel 0.125% Na saccharin solution during the 10 min drinking session and were then exposed to 100 rads of x-radiation. The saccharin solution was presented again on six subsequent Test Days. Phenobarbital in doses of 20, 40, 60 and 80 mg/kg was adminstered 15 min prior to drinking on the first Test Day. Results demonstrate the phenobarbital in all doses tested has a significant attenuating effect on radiation induced taste aversion

  4. Ability of radiation therapists to assess radiation-induced skin toxicity

    International Nuclear Information System (INIS)

    Acharya, Urvi; Cox, Jennifer; Rinks, Marianne; Gaur, Pankaj; Back, Michael

    2013-01-01

    Radiation therapy has seen enhancement of the radiation therapist (RT) role, with RTs and nurses performing duties that were traditionally in the radiation oncologist's (RO) domain. This study aimed to assess whether RTs can consistently grade radiation-induced skin toxicity and their concordance with the gradings given by ROs. Digital photographs of skin reactions were taken at weeks 1, 3 and 6 of radiotherapy on nine patients with breast cancer. The randomly ordered photographs were reviewed once by eight ROs and four RO registrars and on two occasions separated by 6 weeks by 17 RTs. All graded the skin toxicities using the revised Radiation Therapy Oncology Group system. No significant difference was seen between the median scores of the RTs at the first scoring session and the RO/Registrar group. The RTs at both measurement times showed greater inter-rater reliability than the RO/Registrars (W=0.6866, time 1 and 0.6981 time 2, vs. 0.6517), with the experienced RTs the most consistent (W=0.7078). The RTs also showed high intra-rater reliability (rho=0.8461, P<0.0010). These results from RTs with no specific preparation indicate that experienced RTs could assess breast cancer skin toxicity as part of their role.

  5. Understanding the role of p53 in adaptive response to radiation-induced germline mutations

    International Nuclear Information System (INIS)

    Langlois, N.L.; Quinn, J.S.; Somers, C.M.; Boreham, D.R.; Mitchel, R.E.J.

    2003-01-01

    Full text: Radiation-induced adaptive response is now a widely studied area of radiation biology. Studies have demonstrated reduced levels of radiation-induced biological damage when an 'adaptive dose' is given before a higher 'challenge dose' compared to when the challenge dose is given alone. It has been shown in some systems to be a result of inducible cellular repair systems. The adaptive response has been clearly demonstrated in many model systems, however its impact on heritable effects in the mammalian germline has never been studied. Expanded Simple Tandem Repeat (ESTR) loci have been used as markers demonstrating that induced heritable mutations in mice follow a dose-response relationship. Recent data in our laboratory show preliminary evidence of radiation-induced adaptive response suppressing germline mutations at ESTR loci in wild type mice. The frequency of heritable mutations was significantly reduced when a priming dose of 0.1 Gy was given 24 hours prior to a 1 Gy acute challenging dose. We are now conducting a follow-up study to attempt to understand the mechanism of this adaptive response. P53 is known to play a significant role in governing apoptosis, DNA repair and cancer induction. In order to determine what function p53 has in the adaptive response for heritable mutations, we have mated radiation treated Trp53+/- male mice (C57Bl) to untreated, normal females (C57Bl). Using DNA fingerprinting, we are investigating the rate of inherited radiation-induced mutations on pre- and post-meiotic radiation-treated gametocytes by examining mutation frequencies in offspring DNA. If p53 is integral in the mechanism of adaptive response, we should not see an adaptive response in radiation-induced heritable mutations in these mice. This research is significant in that it will provide insight to understanding the mechanism behind radiation-induced adaptive response in the mammalian germline

  6. Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation-induced genomic instability and bystander effects in vitro

    Science.gov (United States)

    Morgan, William F.

    2003-01-01

    A long-standing dogma in the radiation sciences is that energy from radiation must be deposited in the cell nucleus to elicit a biological effect. A number of non-targeted, delayed effects of ionizing radiation have been described that challenge this dogma and pose new challenges to evaluating potential hazards associated with radiation exposure. These effects include induced genomic instability and non-targeted bystander effects. The in vitro evidence for non-targeted effects in radiation biology will be reviewed, but the question as to how one extrapolates from these in vitro observations to the risk of radiation-induced adverse health effects such as cancer remains open.

  7. Radiation-induced cancer of the skin in man

    International Nuclear Information System (INIS)

    Kiyono, Kunihiro; Moriya, Kumiko; Kobayashi, Toshio

    1981-01-01

    Eight cases of radiation induced cancer of the skin observed at the Shinshu University during 30 years from 1951 to 1938 were reported. All of the tumors were squamous cell carcinomas; 7 out of 8 cases occurred in males. Primary conditions for which irradiation was given were 6 cases of benign disorders of various skin disease and 2 cases of spinal tuberculosis. The mean age at which these patients were first subjected to radiation therapy was 31 years. At the time when the diagnosis of skin cancer was established, the mean age was 47 years, with a range from 35 to 58 years. The latent period distributed between 9 and 28 years, with the average of 16.4 years. The estimated radiation doses sufficient to induce cancer of the skin was found to be some thousands R or more, the lowest irradiation dose being about 2,000 R. There was no close correlation between the radiation dose and the latent period, nor between the age of the patient at the time of irradiation and the latent period. The tumors usually occurred in the skin areas where extensive irradiation changes were shown, especially in ulcerative area. (author)

  8. Radiation-induced mutagenicity and lethality in Salmonella typhimurium

    International Nuclear Information System (INIS)

    Isildar, M.; Bakale, G.

    1983-01-01

    The mutagenic and lethal effects of ionizing radiation on histidine-deficient auxotrophs of Salmonella typhimurium were studied to improve the understanding of radiation damage to DNA. The auxotrophs were divided into two groups - one which is sensitive to base-pair substitutions and another sensitive to frameshifts. These groups were composed of parent-daughter pairs in which the chemical mutagenicity enhancing plasmid, pKM101, is absent in the parent strain and present in the daughter. Co-60 #betta#-radiation and 250 kV x-rays were used to irradiate the bacteria. Irradiation of the frameshift - sensitive strains which carry the pKm101 plasmid doubled the absolute number of induced revertants whereas irradiation of the base-pair substitution sensitive strain which also carries the pKm101 plasmid produced nearly no change in the number of induced revertants. A nearly negligible effect on the mutation rate was observed for all parent strains

  9. Hypofractionated stereotactic photon radiotherapy of posteriorly located choroidal melanoma with five fractions at ten Gy – Clinical results after six years of experience

    International Nuclear Information System (INIS)

    Dunavoelgyi, Roman; Zehetmayer, Martin; Gleiss, Andreas; Geitzenauer, Wolfgang; Kircher, Karl; Georg, Dietmar; Schmidt-Erfurth, Ursula; Poetter, Richard; Dieckmann, Karin

    2013-01-01

    Purpose: To evaluate long-term safety and efficacy of hypofractionated stereotactic photon radiotherapy with 5 five fractions at 10 Gy each in patients with centrally located choroidal melanoma. Materials and Methods: Ninety-one patients with centrally located choroidal melanoma were treated stereotactically at a linear accelerator with 6 MV photon beams with 5 fractions at 10 Gy each. Examinations were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and yearly thereafter. Median follow-up was 37.8 months (IQR 19.2–49.9). They included visual acuity assessment, routine ophthalmological examinations with fundoscopy, echography for measurement of tumor dimensions, medical examinations and, if necessary, fluorescein angiography. Results: Initial tumor base diameters, height and volume were 11.20 mm (IQR 9.10–13.70), 9.80 mm (IQR 7.80–11.70), 4.53 mm (IQR 3.33–6.43) and 253.8 mm 3 (IQR 127.5–477.0). Local tumor control and eye retention rates were 97.7% and 86.4% after 5 years, respectively. Eight patients developed metastatic disease and 3 of them died due to metastatic disease during the follow-up period. Median visual acuity decreased from 0.67 initially to 0.05 at the last individual follow-up (p < 0.001). The most common toxicities (any grade) were radiation retinopathy (n = 39), optic neuropathy (n = 32), radiogenic cataract (n = 21), neovascular glaucoma (n = 15) and dry eye syndrome (n = 10). The 5 year probabilities to remain free of these side effects (any grade) were 26.0%, 45.4%, 55.4%, 72.6% and 80.5%, respectively. The most important prognostic factors for toxicities were the largest tumor base diameter, tumor height and tumor distance to the optic disk. Conclusion: Hypofractionated stereotactic photon radiotherapy with a total dose of 50 Gy delivered in 5 fractions is a highly effective treatment option in patients with centrally located choroidal melanoma and has a moderate toxicity profile

  10. State-dependent interaction in the antihistamine-induced disruption of a radiation-induced conditioned taste aversion

    International Nuclear Information System (INIS)

    Rabin, B.M.; Hunt, W.A.; Lee, J.

    1982-01-01

    Two experiments were run to evaluate the possibility that injection of antihistamine can produce a state-dependent acquisition of a radiation-induced conditioned taste aversion. In the first experiment, pretreating rats with the antihistamine chlorpheniramine maleate prior to their initial exposure to sucrose and to low-level irradiation on the conditioning day did not prevent the acquisition of a taste aversion to sucrose when the antihistamine was also administered prior to a subsequent preference test. In the second experiment, rats were both conditioned and tested for a radiation-induced aversion in a drug-free state. Under these condtions, the rats continued to show an aversion to sucrose despite pretreating them with chlorpheniramine prior to irradiation. Since rats conditioned under the antihistamine do not show the radiation-induced conditioned taste aversion when tested for sucrose preference in a nondrug state, it would seem that pretreating rats with an antihistamine prior to conditioning affects only the retrieval of the previously learned response and not its acquisition

  11. UV-B Radiation Induces Root Bending Through the Flavonoid-Mediated Auxin Pathway in Arabidopsis.

    Science.gov (United States)

    Wan, Jinpeng; Zhang, Ping; Wang, Ruling; Sun, Liangliang; Wang, Wenying; Zhou, Huakun; Xu, Jin

    2018-01-01

    Ultraviolet (UV)-B radiation-induced root bending has been reported; however, the underlying mechanisms largely remain unclear. Here, we investigate whether and how auxin and flavonoids are involved in UV-B radiation-induced root bending in Arabidopsis using physiological, pharmacological, and genetic approaches. UV-B radiation modulated the direction of root growth by decreasing IAA biosynthesis and affecting auxin distribution in the root tips, where reduced auxin accumulation and asymmetric auxin distribution were observed. UV-B radiation increased the distribution of auxin on the nonradiated side of the root tips, promoting growth and causing root bending. Further analysis indicated that UV-B induced an asymmetric accumulation of flavonoids; this pathway is involved in modulating the accumulation and asymmetric distribution of auxin in root tips and the subsequent redirection of root growth by altering the distribution of auxin carriers in response to UV-B radiation. Taken together, our results indicate that UV-B radiation-induced root bending occurred through a flavonoid-mediated phototropic response to UV-B radiation.

  12. Radiation-induced erectile dysfunction: Recent advances and future directions

    Directory of Open Access Journals (Sweden)

    Javed Mahmood, PhD

    2016-07-01

    Full Text Available Prostate cancer is one of the most prevalent cancers and the second leading cause of cancer-related deaths in men in the United States. A large number of patients undergo radiation therapy (RT as a standard care of treatment; however, RT causes erectile dysfunction (radiation-induced erectile dysfunction; RiED because of late side effects after RT that significantly affects quality of life of prostate cancer patients. Within 5 years of RT, approximately 50% of patients could develop RiED. Based on the past and current research findings and number of publications from our group, the precise mechanism of RiED is under exploration in detail. Recent investigations have shown prostate RT induces significant morphologic arterial damage with aberrant alterations in internal pudendal arterial tone. Prostatic RT also reduces motor function in the cavernous nerve which may attribute to axonal degeneration may contributing to RiED. Furthermore, the advances in radiogenomics such as radiation induced somatic mutation identification, copy number variation and genome-wide association studies has significantly facilitated identification of biomarkers that could be used to monitoring radiation-induced late toxicity and damage to the nerves; thus, genomic- and proteomic-based biomarkers could greatly improve treatment and minimize arterial tissue and nerve damage. Further, advanced technologies such as proton beam therapy that precisely target tumor and significantly reduce off-target damage to vital organs and healthy tissues. In this review, we summarize recent advances in RiED research and novel treatment modalities for RiED. We also discuss the possible molecular mechanism involved in the development of RiED in prostate cancer patients. Further, we discuss various readily available methods as well as novel strategies such as stem cell therapies, shockwave therapy, nerve grafting with tissue engineering, and nutritional supplementations might be used to

  13. Effect of bFGF on radiation-induced apoptosis of vascular endothelial cells

    International Nuclear Information System (INIS)

    Gu Qingyang; Wang Dewen; Li Yuejuan; Peng Ruiyun; Dong Bo; Wang Zhaohai; Liu Jie; Deng Hua; Jiang Tao

    2003-01-01

    Objective: To study the effect of bFGF on radiation-induced apoptosis vascular endothelial cells. Methods: A cell line PAE (porcine aortic endothelial cells) and primary cultured HUVEC (human umbilical vein endothelial cells) were irradiated with 60 Co γ-rays to establish cell apoptosis models. Flow cytometry with annexin-V-FITC + PI labeling was used to evaluate cell apoptosis. Different amounts of bFGF were used to study their effects on radiation-induced endothelial cell apoptosis. Results and Conclusions: It is found that bFGF could inhibit radiation-induced endothelial cell apoptosis in a considerable degree

  14. Radiation-induced cell mutations as a function of dose rate

    International Nuclear Information System (INIS)

    Kiefer, J.

    1987-01-01

    A brief review of the data in the literature is presented and forms the background of the experimental data given by the author obtained with exponential long-term cultures of V79 hamster cells exposed over a period of up to 35 days to different dose rates of gamma radiation. The experimental results show that at a dose rate of 40 mGy/hour the number of induced mutations is reduced, - which is in agreement with literature data - , but a dose rate of less than 30 mGy/hour makes the induced mutations leap to a value clearly higher than those induced by acute irradiation. As in addition to the mutations recombination is a significant factor of the radiation risk, experiments with a heterozygotic yeast strain have been made, as there is to date no reliable mammalian cell system available for this kind of research. Long-term radiation exposure of the yeast cells over a period of six weeks drastically increased the rate of recombinations, to a value higher by a factor of about 4 than that induced by acute irradiation. (orig.) [de

  15. Origin of specific chromosome aberration in radiation-induced leukemia

    International Nuclear Information System (INIS)

    Ban, Nobuhiko; Kai, Michiaki; Masuno, Yoko

    2005-01-01

    The theme in the title is discussed from the four aspects of specific chromosome aberration (sAb) patterns in radiation-induced leukemia (RIL), possibility for radiation to induce the sAb in RIL, any evidence for participation of delayed aberration to form sAb and the proportion of such healthy humans as having the specifically rearranged genome. Data of sAb observed in leukemia of 25 A-bomb survivors and of 38 patients post radiotherapy of cancers give a rather common pattern. However, many inconsistent results are obtained for sAb in patients post radiotherapy, A-bomb survivors, residents living in radio-contaminated houses in Taipei, in vitro exposure, and Chernobyl residents. At present, any clear evidence is available neither for sAb derived from the delayed aberration nor for estimating the proportion with the specifically rearranged gene. As above, it is unlikely that radiation induces such a translocation abnormality as BCR-ABL specifically seen in leukemia, and this aspect will be important for studies on the genesis of RIL and its risk assessment. (S.I.)

  16. An integrated model for radiation induced cancer

    International Nuclear Information System (INIS)

    Hall, E.J.; Varma, M.

    1994-01-01

    Risk estimates for radiation induced cancer are based on epidemiological data, principally the Japanese A bomb survivors. These estimates for radiation are better known than for any other environmental pollutant, but they do not relate directly to exposure to low doses and low dose rate. Recent rapid advances in molecular genetics, coupled with steady gains in cellular biology, radiation physics and chemistry led to the notion that the time may not be far off when it may be possible to arrive at human cancer risk estimates entirely from laboratory data. Whether risk estimates based on laboratory data will ever replace estimates based on epidemiological studies is an open question. What is clear is that laboratory data can supplement the present risk estimates by providing information on the relative effectiveness of high LET radiations, the importance of dose rate and dose protraction, and by identifying subpopulations which are unusually sensitive or resistant to radiation carcinogenesis. (author)

  17. GSK-3β Inhibition Attenuates LPS-Induced Death but Aggravates Radiation-Induced Death via Down-Regulation of IL-6

    Directory of Open Access Journals (Sweden)

    Bailong Li

    2013-12-01

    Full Text Available Background: Exposure of high dose ionizing radiation is lethal. Signal pathways involved in radiation biology reaction still remain illdefined. Lipopolysaccharides (LPS, the ligands of Toll-like receptor 4(TLR4, could elicit strong immune responses. Glycogen synthase kinase-3β(GSK-3β promotes the production of inflammatory molecules and cell migration. Inhibition of GSK-3β provides protection against inflammation in animal models. The aim of the study was to investigate role of GSK-3β in LPS shock and ionizing radiation. Methods: WT or IL-6-/-mice or cells were pretreated with SB216763, a GSK-3β inhibitor, and survival of the mice was determined. Cell viability was assayed by Cell Counting Kit. Apoptosis was assayed by Annexin V-PI double staining. Serum concentrations of IL-6 and TNF-α were determined by ELISA. Results: SB216763 attenuated LPS induced mice or cell death but aggravated radiation induced mice or cell death. SB216763 reduced IL-6, but not TNF-α levels in vivo. IL-6-/- mice were more resistant to LPS-induced death but less resistant to radiation-induced death than wild type mice. Conclusions: Inhibition of GSK-3β conferred resistance to LPS shock but fostered death induced by ionizing radiation. Inhibition of GSK-3β was effective by reducing IL-6.

  18. Radiation induced effects in the developing central nervous system

    International Nuclear Information System (INIS)

    Gisone, P.; Dubner, D.; Michelin, S.C.; Perez, M.R. Del

    1997-01-01

    The embryo and the human foetus are particularly sensitive to ionizing radiation and this sensitivity presents various qualitative and quantitative functional changes during intra-uterine development. Apart from radiation induced carcinogenesis, the most serious consequence of prenatal exposure in human beings is severe mental retardation. The principal data on radiation effects on human beings in the development of the central nervous system come form epidemiological studies carried out in individuals exposed in utero during the atomic explosion at Hiroshima and Nagasaki. These observations demonstrate the existence of a time of maximum radiosensitivity between the weeks 8 and 15 of the gestational period, a period in which the proliferation and neuronal migration takes place. Determination of the characteristics of dose-response relationship and the possible existence of a threshold dose of radiation effects on the development of the central nervous system is relevant to radiation protection against low dose radiation and the establishment of dose limits for occupational exposure and the public. Studies were conducted on the generation of nitrous-oxide and its relation with the production of active species of oxygen in brains of exposed rats in utero exposed to doses of up to 1 Gy during their maximum radiosensitivity. The possible role of the mechanism of radiation induced damage in the development of the central nervous system is discussed

  19. Phantom-to-clinic development of hypofractionated stereotactic body radiotherapy for early-stage glottic laryngeal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Chuxiong [Department of Radiation Oncology, Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (United States); Chun, Stephen G. [Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Sumer, Baran D. [Department of Otolaryngology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Nedzi, Lucien A.; Abdulrahman, Ramzi E. [Department of Radiation Oncology, Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (United States); Yordy, John S. [Valley Radiation Therapy Center, Anchorage, AK (United States); Lee, Pam; Hrycushko, Brian [Department of Radiation Oncology, Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (United States); Solberg, Timothy D. [Department of Radiation Oncology, Abramson Comprehensive Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA (United States); Ahn, Chul [Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (United States); Timmerman, Robert D. [Department of Radiation Oncology, Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (United States); Schwartz, David L., E-mail: david.schwartz214@gmail.com [Department of Radiation Oncology, Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (United States)

    2017-07-01

    The purpose of this study was to commission and clinically test a robotic stereotactic delivery system (CyberKnife, Sunnyvale, CA) to treat early-stage glottic laryngeal cancer. We enrolled 15 patients with cTis-T2N0M0 carcinoma of the glottic larynx onto an institutional review board (IRB)-approved clinical trial. Stereotactic body radiotherapy (SBRT) plans prescribed 45 Gy/10 fractions to the involved hemilarynx. SBRT dosimetry was compared with (1) standard carotid-sparing laryngeal intensity-modulated radiation therapy (IMRT) and (2) selective hemilaryngeal IMRT. Our results demonstrate that SBRT plans improved sparing of the contralateral arytenoid (mean 20.0 Gy reduction, p <0.001), ipsilateral carotid D{sub max} (mean 20.6 Gy reduction, p <0.001), contralateral carotid D{sub max} (mean 28.1 Gy reduction, p <0.001), and thyroid D{sub mean} (mean 15.0 Gy reduction, p <0.001) relative to carotid-sparing IMRT. SBRT also modestly improved dose sparing to the contralateral arytenoid (mean 4.8 Gy reduction, p = 0.13) and spinal cord D{sub max} (mean 4.9 Gy reduction, p = 0.015) relative to selective hemilaryngeal IMRT plans. This “phantom-to-clinic” feasibility study confirmed that hypofractionated SBRT treatment for early-stage laryngeal cancer can potentially spare dose to adjacent normal tissues relative to current IMRT standards. Clinical efficacy and toxicity correlates continue to be collected through an ongoing prospective trial.

  20. Appearance of radiation-induced lesions after radiotherapy for Hodgkin's disease of the mediastinum and lungs

    Energy Technology Data Exchange (ETDEWEB)

    Zomer-Drozda, J [Instytut Onkologii, Warsaw (Poland)

    1976-01-01

    The incidence of radiation-induced lesions of lung tissue adjacent to the mediastinum and covered by radiation was established on the basis of a retrospective analysis of radiograms of 245 patients treated at the Institute of Oncology in Warsaw in the years 1951-1968, who received radiotherapy to the mediastinal lymph nodes. The radiation-induced lesions were divided into 4 grades depending on their extent and intensity of pulmonary tissue damage. Criteria for classification of radiation-induced fibrosis into the above mentioned grades were established. The correlation between radiation-induced injury and the doses of X-rays applied to the mediastinal lymph nodes was analysed. The importance of radiation-induced changes in the mediastinum and lungs for the diagnosis of recurrences in the irradiated fields, in the marginal areas and granulomatous infiltrations in pulmonary tissue is discussed.