A dose-surviving fraction curve for mouse colonic mucosa

International Nuclear Information System (INIS)

Tucker, S.L.; Thames, H.D. Jr.; Withers, H.R.; Mason, K.A.

1983-01-01

A dose-surviving fraction curve representing the response of the mouse colonic mucosa to single doses of 137 Cs gamma radiation was obtained from the results of a multifraction in vivo colony assay. Construction of the curve required an estimated of the average number of clonogens initially present per colonic crypt. The estimated clonogen count (88) was determined by a statistical method based on the use of doses per fraction common to different fractionation protocols. Parameters for the LQ and TC models of cell survival were obtained by weighted least-squares fits to the data. A comparison of the survival characteristics of cells from the mouse colonic and jejunal crypts suggested that the epithelium of the colon is less radiosensitive than that of the jejunum. (author)

Vaccine vial stopper performance for fractional dose delivery of vaccines.

Science.gov (United States)

Jarrahian, Courtney; Myers, Daniel; Creelman, Ben; Saxon, Eugene; Zehrung, Darin

2017-07-03

Shortages of vaccines such as inactivated poliovirus and yellow fever vaccines have been addressed by administering reduced-or fractional-doses, as recommended by the World Health Organization Strategic Advisory Group of Experts on Immunization, to expand population coverage in countries at risk. We evaluated 3 kinds of vaccine vial stoppers to assess their performance after increased piercing from repeated withdrawal of doses needed when using fractional doses (0.1 mL) from presentations intended for full-dose (0.5 mL) delivery. Self-sealing capacity and fragmentation of the stopper were assessed via modified versions of international standard protocols. All stoppers maintained self-sealing capacity after 100 punctures. The damage to stoppers measured as the fragmentation rate was within the target of ≤ 10% of punctures resulting in a fragment after as many as 50 punctures. We concluded that stopper failure is not likely to be a concern if existing vaccine vials containing up to 10 regular doses are used up to 50 times for fractional dose delivery.

Acoustic neuromas: single dose vs fractionated therapy

Energy Technology Data Exchange (ETDEWEB)

Fuss, M; Debus, J; Lohr, F; Engenhart-Cabillic, R; Wannenmacher, M

1997-07-01

Purpose: Radiosurgical treatment (RS) of acoustic neuromas is a well established treatment. However, few data are available concerning conformal fractionated radiotherapy (FT) of this tumor entity. We evaluated treatment outcome and toxicity for both treatment modalities in 41 patients treated at our institution between 1984 and 1997. Material and Methods: All treatments were performed using a specially adapted linear accelerator and circular collimators for convergent beam RS or multi-leaf collimators (leaf thickness 1 or 3mm) for multi-field RS or fractionated treatment. 22 patients (7 male, 15 female, median age 60 years, range 20-83 years) were treated radiosurgically with single doses between 7 and 28 Gray (median 15 Gy) prescribed to the 80% isodose line. Tumor volumes ranged from 0.7 to 10.5 ccm with a median volume of 3.4 ccm. The median number of isocenters was 2 (1-4 isocenters). One patient was treated by a multi-field technique (14 isocentric irregularly shaped noncoplanar fields). 19 patients (5 male, 14 female, median age 55 years, range 20-81 years) were treated with stereotactic conformal radiotherapy. Median dose was 60 Gray with a median daily fraction size of 2 Gy and a median of 3 (1-4) irregularly shaped isocentric fields. Tumor volumes ranged from 0.7 to 32.4 ccm (median 15 ccm). Median follow-up was 30 months (7-149 months) for radiosurgical and 30 months (2-88 months) for fractionated treatment. Seven patients who underwent fractionated treatment had previously undergone neurosurgical resection on the contralateral side. One had undergone radiosurgery on the opposite side before. Results: All tumors were locally controlled. A volume reduction of more than 20% was seen in 16% after RS and 18% following FT. Typical posttherapeutic central reduction of contrast media enhancement was found in 73% following RS after a median of 8 (3-12) months and in 63% following FT after a median of 6 (1-12) months. Temporary brainstem edema was diagnosed in 4

The optimal fraction size in high-dose-rate brachytherapy: dependency on tissue repair kinetics and low-dose rate

International Nuclear Information System (INIS)

Sminia, Peter; Schneider, Christoph J.; Fowler, Jack F.

2002-01-01

Background and Purpose: Indications of the existence of long repair half-times on the order of 2-4 h for late-responding human normal tissues have been obtained from continuous hyperfractionated accelerated radiotherapy (CHART). Recently, these data were used to explain, on the basis of the biologically effective dose (BED), the potential superiority of fractionated high-dose rate (HDR) with large fraction sizes of 5-7 Gy over continuous low-dose rate (LDR) irradiation at 0.5 Gy/h in cervical carcinoma. We investigated the optimal fraction size in HDR brachytherapy and its dependency on treatment choices (overall treatment time, number of HDR fractions, and time interval between fractions) and treatment conditions (reference low-dose rate, tissue repair characteristics). Methods and Materials: Radiobiologic model calculations were performed using the linear-quadratic model for incomplete mono-exponential repair. An irradiation dose of 20 Gy was assumed to be applied either with HDR in 2-12 fractions or continuously with LDR for a range of dose rates. HDR and LDR treatment regimens were compared on the basis of the BED and BED ratio of normal tissue and tumor, assuming repair half-times between 1 h and 4 h. Results: With the assumption that the repair half-time of normal tissue was three times longer than that of the tumor, hypofractionation in HDR relative to LDR could result in relative normal tissue sparing if the optimum fraction size is selected. By dose reduction while keeping the tumor BED constant, absolute normal tissue sparing might therefore be achieved. This optimum HDR fraction size was found to be largely dependent on the LDR dose rate. On the basis of the BED NT/TUM ratio of HDR over LDR, 3 x 6.7 Gy would be the optimal HDR fractionation scheme for replacement of an LDR scheme of 20 Gy in 10-30 h (dose rate 2-0.67 Gy/h), while at a lower dose rate of 0.5 Gy/h, four fractions of 5 Gy would be preferential, still assuming large differences between tumor

Advantage of dose fractionation in monoclonal antibody-targeted radioimmunotherapy

International Nuclear Information System (INIS)

Schlom, J.; Molinolo, A.; Simpson, J.F.; Siler, K.; Roselli, M.; Hinkle, G.; Houchens, D.P.; Colcher, D.

1990-01-01

Monoclonal antibody (MAb) B72.3 IgG was radiolabeled with 131I and administered to female athymic NCr-nu mice bearing the LS-174T human colon adenocarcinoma xenograft to determine if fractionation of MAb dose had any advantage in tumor therapy. In the LS-174T xenograft, only approximately 30%-60% of tumor cells express the B72.3-reactive TAG-72 antigen. The LS-174T xenograft was used to reflect the heterogeneity of the TAG-72 antigen often seen in biopsy specimens from patients. In contrast to a single 600-muCi dose of 131I-B72.3 IgG where 60% of the animals died from toxic effects, two 300-muCi doses of 131I-B72.3 IgG reduced or eliminated tumor growth in 90% of mice, with only 10% of the animals dying from toxic effects. Dose fractionation even permitted escalation of the dose to three doses of 300 muCi of 131I-B72.3 IgG, resulting in even more extensive tumor reduction or elimination and minimal toxic effects. The use of an isotype-matched control MAb revealed a nonspecific component to tumor growth retardation, but the use of the specific B72.3 IgG demonstrated a much greater therapeutic effect. Tumors that had escaped MAb therapy were analyzed for expression of the B72.3-reactive TAG-72 antigen with the use of the immunoperoxidase method; they were shown to have the same antigenic phenotype as the untreated tumors. We verified tumor elimination by killing the test animals after a 7-week observation period and performing histologic examination of tumor sites. We also monitored toxic effects by histologic examination of numerous organs. These studies thus demonstrate the advantage of dose fractionation of a radiolabeled MAb for tumor therapy. We anticipate that the concept of dose fractionation can be practically applied in radioimmunotherapeutic clinical trials with the development and use of recombinant-chimeric MAbs and modified constructs

Low or High Fractionation Dose {beta}-Radiotherapy for Pterygium? A Randomized Clinical Trial

Energy Technology Data Exchange (ETDEWEB)

Viani, Gustavo Arruda, E-mail: gusviani@gmail.com [Department of Radiation Oncology, Marilia Medicine School, Sao Paulo, SP (Brazil); De Fendi, Ligia Issa; Fonseca, Ellen Carrara [Department of Ophthalmology, Marilia Medicine School, Sao Paulo, SP (Brazil); Stefano, Eduardo Jose [Department of Radiation Oncology, Marilia Medicine School, Sao Paulo, SP (Brazil)

2012-02-01

Purpose: Postoperative adjuvant treatment using {beta}-radiotherapy (RT) is a proven technique for reducing the recurrence of pterygium. A randomized trial was conducted to determine whether a low fractionation dose of 2 Gy within 10 fractions would provide local control similar to that after a high fractionation dose of 5 Gy within 7 fractions for surgically resected pterygium. Methods: A randomized trial was conducted in 200 patients (216 pterygia) between February 2006 and July 2007. Only patients with fresh pterygium resected using a bare sclera method and given RT within 3 days were included. Postoperative RT was delivered using a strontium-90 eye applicator. The pterygia were randomly treated using either 5 Gy within 7 fractions (Group 1) or 2 Gy within 10 fractions (Group 2). The local control rate was calculated from the date of surgery. Results: Of the 216 pterygia included, 112 were allocated to Group 1 and 104 to Group 2. The 3-year local control rate for Groups 1 and 2 was 93.8% and 92.3%, respectively (p = .616). A statistically significant difference for cosmetic effect (p = .034), photophobia (p = .02), irritation (p = .001), and scleromalacia (p = .017) was noted in favor of Group 2. Conclusions: No better local control rate for postoperative pterygium was obtained using high-dose fractionation vs. low-dose fractionation. However, a low-dose fractionation schedule produced better cosmetic effects and resulted in fewer symptoms than high-dose fractionation. Moreover, pterygia can be safely treated in terms of local recurrence using RT schedules with a biologic effective dose of 24-52.5 Gy{sub 10.}.

Fractionation in medium dose rate brachytherapy of cancer of the cervix

International Nuclear Information System (INIS)

Leborgne, Felix; Fowler, Jack F.; Leborgne, Jose H.; Zubizarreta, Eduardo; Chappell, Rick

1996-01-01

Purpose: To establish an optimum fractionation for medium dose rate (MDR) brachytherapy from retrospective data of patients treated with different MDR schedules in comparison with a low dose rate (LDR) schedule. Methods and Materials: The study population consists of consecutive Stage IB-IIA-IIB patients who received radiotherapy alone with full dose brachytherapy plus external beam pelvic and parametrial irradiation from 1986-1993. Patients also receiving surgery or chemotherapy were excluded. The LDR group (n = 102, median follow-up: 80 months) received a median dose to Point A of two 32.5 Gy fractions at 0.44 Gy/h plus 18 Gy of external whole pelvic irradiation. The MDR1 group (n = 30, median follow-up: 45 months) received a mean dose of two 32 Gy fractions at 1.68 Gy/h. An individual dose reduction of 12.5% was planned for this group according to the Manchester experience, but only a 4.8% dose reduction was achieved. The MDR2 group (n = 10, median follow-up: 36 months) received a dose of two 24 Gy fractions at 1.65 Gy/h. The MDR3 group (n = 10, median follow-up 33 months) received a mean dose of three 15.3 Gy fractions at 1.64 Gy/h. And finally, the MDR4 group (n = 38, median follow-up: 24 months) received six 7.7 Gy fractions from two pulses 6 h apart in each of three insertions at 1.61 Gy/h. The median external pelvic dose to MDR schedules was between 12 and 20 Gy. The linear quadratic (LQ) formula was used to calculate the biologically effective dose (BED) to tumor (Gy 10 ) and rectum (Gy 3 ), assuming T(1(2)) for repair = 1.5 h. Results: The crude central recurrence rate was 6% for LDR (mean BED = 95.4 Gy 10 ) and 10% for MDR4 (mean BED = 77.0 Gy 10 ) (p = NS). The remaining MDR groups had no recurrences. Grade 2 and 3 rectal or bladder complications were 0% for LDR (rectal BED = 109 Gy 3 ), 83% for MDR1 (BED = 206 Gy 3 ), and 30% for MDR3 (BED = 127 Gy 3 ). The MDR2 and MDR4 groups presented no complications (BED, 123 Gy 3 , and 105 Gy 3 , respectively

Recalculation of dose for each fraction of treatment on TomoTherapy.

Science.gov (United States)

Thomas, Simon J; Romanchikova, Marina; Harrison, Karl; Parker, Michael A; Bates, Amy M; Scaife, Jessica E; Sutcliffe, Michael P F; Burnet, Neil G

2016-01-01

The VoxTox study, linking delivered dose to toxicity requires recalculation of typically 20-37 fractions per patient, for nearly 2000 patients. This requires a non-interactive interface permitting batch calculation with multiple computers. Data are extracted from the TomoTherapy(®) archive and processed using the computational task-management system GANGA. Doses are calculated for each fraction of radiotherapy using the daily megavoltage (MV) CT images. The calculated dose cube is saved as a digital imaging and communications in medicine RTDOSE object, which can then be read by utilities that calculate dose-volume histograms or dose surface maps. The rectum is delineated on daily MV images using an implementation of the Chan-Vese algorithm. On a cluster of up to 117 central processing units, dose cubes for all fractions of 151 patients took 12 days to calculate. Outlining the rectum on all slices and fractions on 151 patients took 7 h. We also present results of the Hounsfield unit (HU) calibration of TomoTherapy MV images, measured over an 8-year period, showing that the HU calibration has become less variable over time, with no large changes observed after 2011. We have developed a system for automatic dose recalculation of TomoTherapy dose distributions. This does not tie up the clinically needed planning system but can be run on a cluster of independent machines, enabling recalculation of delivered dose without user intervention. The use of a task management system for automation of dose calculation and outlining enables work to be scaled up to the level required for large studies.

Radiation as an immunological adjuvant: current evidence on dose and fractionation

International Nuclear Information System (INIS)

Demaria, Sandra; Formenti, Silvia C.

2012-01-01

Ionizing radiation to a cancer site has the ability to convert the irradiated tumor in an immunogenic hub. However, radiation is a complex modifier of the tumor microenvironment and, by itself, is seldom sufficient to induce a therapeutically significant anti-tumor immune response, since it can also activate immune suppressive pathways. While several combinations of local radiation and immunotherapy have been shown in pre-clinical models to induce powerful anti-tumor immunity, the optimal strategy to achieve this effect remains to be defined. When used in vivo, radiation effects on tumors depend on the dose per fraction applied, the number of fractions used, and the total dose. Moreover, the interplay of these three variables is contingent upon the tumor setting studied, both in pre-clinical and clinical applications. To enable repair of the collateral damage to the normal tissue, radiation is usually given in multiple fractions, usually of 2 Gy. Generally, the use of larger fractions is limited to stereotactic applications, whereby optimal immobilization reduces inter- and intrafraction movement and permits a very conformal delivery of dose to the target, with optimal exclusion of normal tissue. Translation of the partnership of radiation and immunotherapy to the clinic requires a careful consideration of the radiation regimens used. To date, little is known on whether different dose/fractionation regimens have a specific impact on the anti-tumor immune response. Most experiments combining the two modalities were conducted with single fractions of radiotherapy. However, there is at least some evidencethat when combined with some specific immunotherapy approaches, the ability of radiation to promote anti-tumor immunity is dependent on the dose and fractionation employed. We critically review the available in vitro and in vivo data on this subject and discuss the potential impact of fractionation on the ability of radiation to synergize with immunotherapy.

Linear-quadratic model underestimates sparing effect of small doses per fraction in rat spinal cord

International Nuclear Information System (INIS)

Shun Wong, C.; Toronto University; Minkin, S.; Hill, R.P.; Toronto University

1993-01-01

The application of the linear-quadratic (LQ) model to describe iso-effective fractionation schedules for dose fraction sizes less than 2 Gy has been controversial. Experiments are described in which the effect of daily fractionated irradiation given with a wide range of fraction sizes was assessed in rat cervical spine cord. The first group of rats was given doses in 1, 2, 4, 8 and 40 fractions/day. The second group received 3 initial 'top-up'doses of 9 Gy given once daily, representing 3/4 tolerance, followed by doses in 1, 2, 10, 20, 30 and 40 fractions/day. The fractionated portion of the irradiation schedule therefore constituted only the final quarter of the tolerance dose. The endpoint of the experiments was paralysis of forelimbs secondary to white matter necrosis. Direct analysis of data from experiments with full course fractionation up to 40 fractions/day (25.0-1.98 Gy/fraction) indicated consistency with the LQ model yielding an α/β value of 2.41 Gy. Analysis of data from experiments in which the 3 'top-up' doses were followed by up to 10 fractions (10.0-1.64 Gy/fraction) gave an α/β value of 3.41 Gy. However, data from 'top-up' experiments with 20, 30 and 40 fractions (1.60-0.55 Gy/fraction) were inconsistent with LQ model and gave a very small α/β of 0.48 Gy. It is concluded that LQ model based on data from large doses/fraction underestimates the sparing effect of small doses/fraction, provided sufficient time is allowed between each fraction for repair of sublethal damage. (author). 28 refs., 5 figs., 1 tab

Short-term irradiation of the glioblastoma with high-dosed fractions

International Nuclear Information System (INIS)

Hinkelbein, W.; Bruggmoser, G.; Schmidt, M.; Wannenmacher, M.

1984-01-01

Compared to surgery alone, postoperative radiotherapy leads with glioblastomas (grade IV gliomas) to a significant improvement of the therapeutic results. The prolongation of survival time, however, is to a large extent compensated by the therapy itself (it normally implicates hospitalisation). Therefore, we tested the efficiency of rapid course irradiation with high fractions. 70 patients were treated daily with individual fractions of 3.5 Gy, 4 to 6 fractions per week. The entire dose amounted to 31.5 to 38.5 Gy. The average survival time was 33.5 weeks corresponding to the survival time known from the combined surgical and radiotherapeutical treatment of glioblastomas. An effective increase in therapy-free survival time seems possible, especially when the entire focal dose does not exceed 35 Gy. It is remarkable that the patients with the maximum exposure did not have the longest survival times and rates. Living conditions for the patients were similar to those with conventional fractioning, or even better. Rapid course irradiation with high fractions and a limited total dose (35 Gy) presently is - apart from the accelerated superfractioning - a successful measure to prolong the therapyfree survival time for patients with grade IV gliomas. (orig.) [de

Changes in tumor cell response due to prolonged dose delivery times in fractionated radiation therapy

International Nuclear Information System (INIS)

Paganetti, Harald

2005-01-01

Purpose: Dynamic radiation therapy, such as intensity-modulated radiation therapy, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The cellular damage after a full treatment may depend on the dose rate, because sublethal radiation damage can be repaired more efficiently during prolonged dose delivery. The goal of this study was to investigate the significance of this effect in fractionated radiation therapy. Methods and Materials: The lethal/potentially lethal model was used to calculate lesion induction rates for repairable and nonrepairable lesions. Dose rate effects were analyzed for 9 different cell lines (8 human tumor xenografts and a C3H10T1/2 cell line). The effects of single-fraction as well as fractionated irradiation for different dose rates were studied. Results: Significant differences can be seen for dose rates lower than about 0.1 Gy/min for all cell lines considered. For 60 Gy delivered in 30 fractions, the equivalent dose is reduced by between 1.3% and 12% comparing 2 Gy delivery over 30 min per fraction with 2 Gy delivery over 1 min per fraction. The effect is higher for higher doses per fraction. Furthermore, the results show that dose rate effects do not show a simple correlation with the α/β ratio for ratios between 3 Gy and 31 Gy. Conclusions: If the total dose delivery time for a treatment fraction in radiation therapy increases to about 20 min, a correction for dose rate effects may have to be considered in treatment planning. Adjustments in effective dose may be necessary when comparing intensity-modulated radiation therapy with conventional treatment plans

Response of pig skin to fractionated radiation doses

International Nuclear Information System (INIS)

Wiernik, G.; Hopewell, J.W.; Patterson, T.J.S.; Young, C.M.A.; Foster, J.L.

1977-01-01

The individual components of a fractionated course of irradiation treatment have been considered separately. Methods of accurate measurement of individual parameters has brought to light different interpretations of the observations. Reasons are given for the necessity of having a radiobiological model which has a direct relevance to the clinical situation. Results are reported for fractionated regimes of irradiation in which the dose has been varied above and below normal tissue tolerance which has been equated with clinical skin necrosis. The components of the acute skin reaction, erythema, pigmentation and desquamation have been analysed separately and their contribution as a method of measurement assessed. Initially, the range of numerical scores attributed to erythema did not reach the scores attributed to necrosis but we now believe that radiation damage expressed as erythema can move directly into necrosis without passing through desquamation. Desquamation, on the other hand, only became a useful parameter at higher dose levels; it has also been shown to be a component associated with skin breakdown. Pigmentation showed no dose response at the dose levels employed in our experiments and it is our belief that this is due to this system being fully saturated under these circumstances. Measurement of the late radiation reaction in the skin has been considered in detail and our results have been expressed by comparing the relative lengths of irradiated and control fields in the same pig. From these findings iso-effect graphs have been constructed and time and fractionation factors have been derived. (author)

Decreased uptake after fractionated ablative doses of iodine-131

Energy Technology Data Exchange (ETDEWEB)

Wu, Hurng-Sheng [Show Chwan Memorial Hospital, Department of Surgery, Changhua, Taiwan (Taiwan); Hseu, Huey-Herng [Taichung Veterans General Hospital, Department of Medical Education and Research, Taichung (Taiwan); Lin, Wan-Yu; Wang, Shyh-Jen [Taichung Veterans General Hospital, Department of Nuclear Medicine, Taichung, Taiwan (Taiwan); Liu, Yao-Chi [Department of Surgery, General Surgery, National Defense Medical Center, Taipe (Taiwan)

2005-02-01

In an attempt to obviate the necessity for hospitalisation, the ablative dose of {sup 131}I in the treatment of thyroid cancer is divided into two or three fractions at weekly intervals in some hospitals with no special bed for {sup 131}I treatment. Thyroid stunning has been observed in patients receiving a {sup 131}I dose between 74 and 370 MBq (2-10 mCi). However, the influence of {sup 131}I uptake after administration of a higher dose, such as 1,110-1,850 MBq of {sup 131}I, has never been reported. In this study, we evaluated the degree of reduction in {sup 131}I uptake after patients received 1,480 MBq of {sup 131}I and evaluated the clinical value of fractionated ablative doses of {sup 131}I. Thirty-five patients with functional thyroid cancer received a total of 4,440 MBq (120 mCi) of {sup 131}I which was divided into three fractions administered at weekly intervals. In all patients two {sup 131}I whole-body scans were performed. The first scan was performed directly prior to the second dose of {sup 131}I (7 days after the first administration of {sup 131}I), and the second scan was performed 7 days after the second administration of {sup 131}I and directly prior to the third administration. Regions of interest including the neck and lungs were drawn to calculate the uptake of {sup 131}I in the thyroid remnant and possible cervical lymph node and lung metastases. The mean uptake of {sup 131}I was 2.73% 7 days after the first administration, and decreased significantly to 0.26% 7 days after the second administration. The mean decrease was as high as 80.7%. The decrease in {sup 131}I uptake was significant in all patients except the two with lung metastases. In the two patients with lung metastases, no definite evidence of decreased uptake was noted; the uptake of {sup 131}I in the lung metastases even increased on the second {sup 131}I image in one of these patients. After administration of 1,480 MBq of {sup 131}I, the decreased uptake was significant in all

Alternate day treatment and late effects: The concept of an effective dose per fraction

International Nuclear Information System (INIS)

Courdi, A.; Hery, M.; Gabillat, J.M.

1990-01-01

Although most institutions treat all fields each day, some radiotherapists continue to adopt an alternate day schedule. The resulting daily variations of the dose per fraction in laterally located targets have been analyzed using the linear-quadratic model. Patients with breast carcinoma treated with definitive radiotherapy in 1974-1975 with one field a day were studied. An effective dose per fraction was derived, with a value higher than the average dose per fraction received by the reference point. The greater the fluctuations between the doses per fraction on successive days, the higher the effective dose per fraction. The corresponding cell survival due to alternate treatment as compared to survival with daily treatment depends on the alpha/beta ratio. For a late effect with low alpha/beta ratio, an alternate treatment may lead to almost 10-fold increase in cell kill in these lateral targets such as those responsible for subcutaneous sclerosis as compared to daily treatment of all fields with the same total dose. Taking the average effective dose per fraction in our series, the increase in cell kill was 4-fold. Acute effects would suffer less damage due to alternate treatment because of a high alpha/beta ratio. Treatment on an alternate schedule should be restricted to palliative radiotherapy

Superfractionation as a potential hypoxic cell radiosensitizer: prediction of an optimum dose per fraction

International Nuclear Information System (INIS)

Dasu, Alexandru; Denekamp, Juliana

1999-01-01

Purpose: A dose 'window of opportunity' has been identified in an earlier modeling study if the inducible repair variant of the LQ model is adopted instead of the pure LQ model, and if all survival curve parameters are equally modified by the presence or absence of oxygen. In this paper we have extended the calculations to consider survival curve parameters from 15 sets of data obtained for cells tested at low doses using clonogenic assays. Methods and Materials: A simple computer model has been used to simulate the response of each cell line to various doses per fraction in multifraction schedules, with oxic and hypoxic cells receiving the same fractional dose. We have then used pairs of simulated survival curves to estimate the effective hypoxic protection (OER') as a function of the dose per fraction. Results: The resistance of hypoxic cells is reduced by using smaller doses per fraction than 2 Gy in all these fractionated clinical simulations, whether using a simple LQ model, or the more complex LQ/IR model. If there is no inducible repair, the optimum dose is infinitely low. If there is inducible repair, there is an optimum dose per fraction at which hypoxic protection is minimized. This is usually around 0.5 Gy. It depends on the dose needed to induce repair being higher in hypoxia than in oxygen. The OER' may even go below unity, i.e. hypoxic cells may be more sensitive than oxic cells. Conclusions: If oxic and hypoxic cells are repeatedly exposed to doses of the same magnitude, as occurs in clinical radiotherapy, the observed hypoxic protection varies with the fractional dose. The OER' is predicted to diminish at lower doses in all cell lines. The loss of hypoxic resistance with superfractionation is predicted to be proportional to the capacity of the cells to induce repair, i.e. their intrinsic radioresistance at a dose of 2 Gy

Response of rat spinal cord to very small doses per fraction: lack of enhanced radiosensitivity

International Nuclear Information System (INIS)

Shun, Wong C.; Yong, Hao; Hill, Richard P.

1995-01-01

Our previous work with rat spinal cord demonstrated that the linear quadratic (LQ) model based on data for large fraction sizes ((α(β)) of 2.4 Gy) failed to predict isoeffective doses between 1 and 2 Gy per fraction, and under-estimated the sparing effect of small doses per fraction given once daily. In contrast, data from mouse skin and kidney, and recent in vitro results revealed a paradoxical increase in radiosensitivity at below 1 Gy per fraction. To assess whether enhanced radiosensitivity is present in the spinal cord below 1 Gy per fraction, the rat spinal cord (C2-T2) was irradiated initially with three daily doses of 10.25 Gy (top-up doses representing 90% of tolerance), followed by graded single doses or fractionated doses in 1.5, 1.0, 0.8, 0.6 or 0.4 Gy fractions given once daily. To limit the overall treatment time to ≤ 8 weeks, a small number of the 0.6- and 0.4-Gy fractions were given twice daily with an interfraction interval of 16 h. The end-point was forelimb paralysis secondary to white matter necrosis, confirmed histologically. The ED 50 values, excluding the top-up doses, were 5.8, 10.6, 14.8, 15.2, 15.9 and 19.1 Gy for a single dose and doses in 1.5-, 1.0-, 0.8-, 0.6- and 0.4-Gy fractions, respectively. The data gave an (α(β)) of 2.1 Gy (95% CI, 1.4, 2.7 Gy). Pooling the data separately, the (α(β)) value was 2.3 Gy (95% CI, 0.82, 3.7 Gy) for fraction sizes ≥ 1 Gy, and 1.2 Gy (95% CI, 0.16, 2.3 Gy) for the 0.8-, 0.6- and 0.4-Gy experiments. These results in which top-up doses were given initially are consistent with a large sparing effect of very small fraction sizes in rat spinal cord provided sufficient time is allowed for repair of sublethal damage between fractions, and provide no evidence for a paradoxical increase in radiosensitivity in the rat spinal cord below 1 Gy down to 0.4 Gy per fraction

Single and 30 fraction tumor control doses correlate in xenografted tumor models: implications for predictive assays

International Nuclear Information System (INIS)

Gerweck, Leo E.; Dubois, Willum; Baumann, Michael; Suit, Herman D.

1995-01-01

Purpose/Objective: In a previous publication we reported that laboratory assays of tumor clonogen number, in combination with intrinsic radiosensitivity measured in-vitro, accurately predicted the rank-order of single fraction 50% tumor control doses, in six rodent and xenografted human tumors. In these studies, tumor hypoxia influenced the absolute value of the tumor control doses across tumor types, but not their rank-order. In the present study we hypothesize that determinants of the single fraction tumor control dose, may also strongly influence the fractionaled tumor control doses, and that knowledge of tumor clonogen number and their sensitivity to fractionated irradiation, may be useful for predicting the relative sensitivity of tumors treated by conventional fractionated irradiation. Methods/Materials: Five tumors of human origin were used for these studies. Special care was taken to ensure that all tumor control dose assays were performed over the same time frame, i.e., in-vitro cells of a similar passage were used to initiate tumor sources which were expanded and used in the 3rd or 4th generation. Thirty fraction tumor control doses were performed in air breathing mice, under normal blood flow conditions (two fractions/day). The results of these studies have been previously published. For studies under uniformly (clamp) hypoxic conditions, tumors arising from the same transplantation were randomized into single or fractionated dose protocols. For estimation of the fractionated TCD50 under hypoxic conditions, tumors were exposed to six 5.4 Gy fractions (∼ 2 Gy equivalent under air), followed by graded 'top-up' dose irradiation for determination of the TCD50; the time interval between doses was 6-9 hours. The single dose equivalent of the six 5.4 Gy doses was used to calculate an extrapolated 30 fraction hypoxic TCD50. Results: Fractionation substantially increased the dose required for tumor control in 4 of the 5 tumors investigated. For these 4 tumors

Reemergence of apoptotic cells between fractionated doses in irradiated murine tumors

International Nuclear Information System (INIS)

Meyn, R.E.; Hunter, N.R.; Milas, L.

1994-01-01

The purpose of this investigation was to follow up our previous studies on the development of apoptosis in irradiated murine tumors by testing whether an apoptotic subpopulation of cells reemerges between fractionated exposures. Mice bearing a murine ovarian carcinoma, OCa-I, were treated in vivo with two fractionation protocols: two doses of 12.5 Gy separated by various times out to 5 days and multiple daily fractions of 2.5 Gy. Animals were killed 4 h after the last dose in each protocol, and the percent apoptosis was scored from stained histological sections made from the irradiated tumors according to the specific features characteristic of this mode of cell death. The 12.5+12.5 Gy protocol yielded a net total percent apoptosis of about 45% when the two doses were separated by 5 days (total dose = 25 Gy), whereas the 2.5 Gy per day protocol yielded about 50% net apoptotic cells when given for 5 days (total dose = 12.5 Gy). These values are to be compared to the value of 36% apoptotic cells that is yielded by large single doses (> 25 Gy). Thus, these results indicate that an apoptotic subpopulation of cells reemerged between the fractions in both protocols, but the kinetics appeared to be delayed in the 12.5+12.5 Gy vs. the multiple 2.5 Gy protocol. This reemergence of cells with the propensity for radiation-induced apoptosis between fractionated exposures is consistent with a role for this mode of cell death in the response of tumors to radiotherapy and may represent the priming of a new subpopulation of tumor cells for apoptosis as part of normal tumor homeostasis to counterbalance cell division. 25 refs., 3 figs., 1 tab

Chromosome aberration yields in human lymphocytes induced by fractionated doses of x-radiation

International Nuclear Information System (INIS)

Purrott, R.J.; Reeder, E.

1976-01-01

Unstimulated (G 0 ) human peripheral blood lymphocytes were exposed at 37degC to doses of 200 or 500 rad of X-rays delivered in two equal fractions. The dose fractions were separated by intervals of up to 7 h in the 200 rad study and up to 48 h for 500 rad. In both studies the mean levels of dicentrics and total unstable aberrations began to decline when fractions were delivered with intervals of greater than 2 h. With 200 rad the yield had decreased to an additive baseline (i.e. equal to only twice the yield of a single 100-rad fraction) by an interval of 4 h. Following 500 rad the yield declined until 8 h and then remained 20% above the expected additive baseline even when 48 h separated the fractions. Possible explanations for this discrepancy are discussed. In a second experiment PHA stimulated lymphocyte cultures were exposed to 2 doses of 125 rad of X-rays up to 7 h apart in an attempt to demonstrate the late peak in aberration yield originally reported by Lane. Control cultures received unsplit doses of 250 rad at the time of the corresponding second 125-rad fraction. No evidence of a late peak in dicentric yield was observed. The yield remained approximately the same irrespective of the time interval between fractions but these split dose yields were significantly different from the accompanying unsplit controls

Induction by X-rays of chromosome aberrations in male guinea-pigs and golden hamsters. 4. Dose-response for spermatogonia treated with fractionated doses

Energy Technology Data Exchange (ETDEWEB)

Lyon, M F; Cox, B D [Medical Research Council, Harwell (UK). Radiobiological Research Unit

1975-10-01

The effect of dose fractionation on the induction of translocations by 400 and 600 rad X-rays in spermatogonia of guinea-pigs and hamsters was investigated cytologically. Three types of fractionation were used, dividing the dose into (a) two equal fractions 24h apart, (b) two equal fractions 8 weeks apart, and (c) eight or twelve equal fractions of 50 rad, at intervals of one week. The two species responded similarly throughout, but gave lower translocation yields than the mouse. The effects of the first and third types of fractionation were similar to those described previously in the mouse, and suggested that a first radiation dose modifies the spermatogonial population so that its sensitivity to a dose 24h later is altered, and that repeated radiation doses result in development of resistance to translocation induction. After 8-week fractionation, the results suggested that in guinea-pigs and hamsters, the spermatogonial population had not returned to normal by 8 weeks after the first dose, whereas in the mouse, normal sensitivity had returned by this time. The results, reported previously, of single doses of X-rays suggest that the spermatogonial population consists of sub-populations differing in sensitivity to cell killing and genetic effects. The effects of fractionated doses in the mouse suggest that the sensitive and resistant types represent different phases of the samecell type rather than two distinct types of cell. In the guinea-pig and hamster, this question remains open.

Effective dose as an irritating influence during fractionated γ-irradiation

International Nuclear Information System (INIS)

Karpov, V.N.; Ushakov, I.B.; Davydov, B.I.

1990-01-01

The study of early neurological disturbances (END) in rats after fractionated γ-irradiation with doses of 37.5-225 Gy at dose rate of 30.11 Gy/min has demonstrated that the initial response of animals to pulse ionizing radiation is a function of the electric charge induced by ionizing radiation. A change in the probability of occurrence of each of the END symptoms, with the increased intervals between exposures, is merely an indirect indication of the eliminating mechanisms and is intricately connected with the irritating charge value. The proposed empiric relationships permit to correlate the probability of END symptom occurrence with the continuous quantitative parameter of fractionated irradiation, that is, with an effective dose as an analogue of the irritating effect

Tumor and normal tissue responses to fractioned non-uniform dose delivery

Energy Technology Data Exchange (ETDEWEB)

Kaellman, P; Aegren, A; Brahme, A [Karolinska Inst., Stockholm (Sweden). Dept. of Radiation Physics

1996-08-01

The volume dependence of the radiation response of a tumor is straight forward to quantify because it depends primarily on the eradication of all its clonogenic cells. A tumor therefore has a parallel organization as any surviving clonogen in principle can repopulate the tumor. The difficulty with the response of the tumor is instead to know the density and sensitivity distribution of the most resistant clonogenic cells. The increase in the 50% tumor control dose and the decrease in the maximum normalized slope of the dose response relation, {gamma}, in presence of small compartments of resistant tumor cells have therefore been quantified to describe their influence on the dose response relation. Injury to normal tissue is a much more complex and gradual process. It depends on earlier effects induced long before depletion of the differentiated and clonogenic cells that in addition may have a complex structural and functional organization. The volume dependence of the dose response relation of normal tissues is therefore described here by the relative seriality, s, of the infrastructure of the organ. The model can also be generalized to describe the response of heterogeneous tissues to non uniform dose distributions. The new model is compared with clinical and experimental data on normal tissue response, and shows good agreement both with regard to the shape of dose response relation and the volume dependence of the isoeffect dose. The response of tumors and normal tissues are quantified for arbitrary dose fractionations using the linear quadratic cell survival parameters {alpha} and {beta}. The parameters of the dose response relation are derived both for a constant dose per fraction and a constant number of dose fractions, thus in the latter case accounting also for non uniform dose delivery. (author). 26 refs, 4 figs.

Accelerated repopulation of mouse tongue epithelium during fractionated irradiations or following single doses

International Nuclear Information System (INIS)

Doerr, W.; Kummermehr, J.

1990-01-01

Mouse tongue mucosa was established as an animal model to study repopulation after large single doses or during continuous irradiation. A top-up irradiation technique was used employing priming doses or fractionated treatment to the whole snout (300 kV X-rays) followed by local test doses (25 kV X-rays) to elicit denudation in a confined field of the inferior tongue surface. Clearcut quantal dose-response curves of ulcer incidence were obtained to all protocols; animal morbidity, i.e. body weight loss was minimal. Repopulation following priming doses of 10 and 13 Gy started with a delay of at least 3 days and then progressed rapidly to nearly restore original tissue tolerance by day 11. During continuous fractionation over 1 to 3 weeks with 5 fractions/week and doses per fraction of 2.5, 3 and 3.5 Gy, repopulation was small in week one but subsequently increased to fully compensate the weekly dose at all dose levels. Additional measurements of cell density during a 4 weeks course of 5 x 3 Gy or 5 x 4 Gy per week showed only moderate depletion to 67% of the control figures. The fact that rapid repopulation is achieved at relatively moderate damage levels should be taken into account when the timing of a treatment split is considered. (author). 18 refs.; 7 figs.; 1 tab

Fractional poisson--a simple dose-response model for human norovirus.

Science.gov (United States)

Messner, Michael J; Berger, Philip; Nappier, Sharon P

2014-10-01

This study utilizes old and new Norovirus (NoV) human challenge data to model the dose-response relationship for human NoV infection. The combined data set is used to update estimates from a previously published beta-Poisson dose-response model that includes parameters for virus aggregation and for a beta-distribution that describes variable susceptibility among hosts. The quality of the beta-Poisson model is examined and a simpler model is proposed. The new model (fractional Poisson) characterizes hosts as either perfectly susceptible or perfectly immune, requiring a single parameter (the fraction of perfectly susceptible hosts) in place of the two-parameter beta-distribution. A second parameter is included to account for virus aggregation in the same fashion as it is added to the beta-Poisson model. Infection probability is simply the product of the probability of nonzero exposure (at least one virus or aggregate is ingested) and the fraction of susceptible hosts. The model is computationally simple and appears to be well suited to the data from the NoV human challenge studies. The model's deviance is similar to that of the beta-Poisson, but with one parameter, rather than two. As a result, the Akaike information criterion favors the fractional Poisson over the beta-Poisson model. At low, environmentally relevant exposure levels (Poisson model; however, caution is advised because no subjects were challenged at such a low dose. New low-dose data would be of great value to further clarify the NoV dose-response relationship and to support improved risk assessment for environmentally relevant exposures. © 2014 Society for Risk Analysis Published 2014. This article is a U.S. Government work and is in the public domain for the U.S.A.

A comparison of anti-tumor effects of high dose rate fractionated and low dose rate continuous irradiation in multicellular spheroids

International Nuclear Information System (INIS)

Kubota, Nobuo; Omura, Motoko; Matsubara, Sho.

1997-01-01

In a clinical experience, high dose rate (HDR) fractionated interstitial radiotherapy can be an alternative to traditional low dose rate (LDR) continuous interstitial radiotherapy for head and neck cancers. To investigate biological effect of HDR, compared to LDR, comparisons have been made using spheroids of human squamous carcinoma cells. Both LDR and HDR were delivered by 137 Cs at 37degC. Dose rate of LDR was 8 Gy/day and HDR irradiations of fraction size of 4, 5 or 6 Gy were applied twice a day with an interval time of more than 6 hr. We estimated HDR fractionated dose of 31 Gy with 4 Gy/fr to give the same biological effects of 38 Gy by continuous LDR for spheroids. The ratio of HDR/LDR doses to control 50% spheroids was 0.82. (author)

Effect of time, dose and fractionation on local control of nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Lee, Anne W.M.; Chan, David K.K.; Poon, Y.F.; Foo, William; Law, Stephen C.K.; O, S.K.; Tung, Stewart Y.; Fowler, Jack F.; Chappell, Rick

1995-01-01

To study the effect of radiation factors on local control of nasopharyngeal carcinoma, 1008 patients with similarly staged T1N0-3M0 disease (Ho's classification) were retrospectively analyzed. All patients were treated by megavoltage irradiation alone using the same technique. Four different fractionation schedules had been used sequentially during 1976-1985: with total dose ranging from 45.6 to 60 Gy and fractional dose from 2.5 to 4.2 Gy. The median overall time was 39 days (range = 38-75 days). Both for the whole series and 763 patients with nodal control, total dose was the most important radiation factor. The hazard of local failure decreased by 9% per additional Gy (p < 0.01). Biological equivalents expressed in terms of Biologically Effective Dose or Nominal Standard Dose also showed strong correlation. Fractional dose had no significant impact. The effect of overall treatment time was insignificant for the whole series, but almost reached statistical significance for those with nodal control (p = 0.06). Further study is required for elucidation, as 85% of patients completed treatment within a very narrow range (38-42 days), and the possible hazard is clinically too significant to be ignored

High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

International Nuclear Information System (INIS)

Deeg, H.J.; Storb, R.; Weiden, P.L.; Schumacher, D.; Shulman, H.; Graham, T.; Thomas, E.D.

1981-01-01

Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors

Justification for inter-fraction correction of catheter movement in fractionated high dose-rate brachytherapy treatment of prostate cancer

International Nuclear Information System (INIS)

Simnor, Tania; Li, Sonia; Lowe, Gerry; Ostler, Peter; Bryant, Linda; Chapman, Caroline; Inchley, Dave; Hoskin, Peter J.

2009-01-01

Background and purpose: Fractionated high dose-rate (HDR) brachytherapy in the treatment of prostate cancer relies on reproducible catheter positions for each fraction to ensure adequate tumour coverage while minimising dose to normal tissues. Peri-prostatic oedema may cause caudal displacement of the catheters relative to the prostate gland between fractions. This can be corrected for by changing source dwell positions or by physical re-advancement of catheters before treatment. Materials and methods: Data for 20 consecutive monotherapy patients receiving three HDR fractions of 10.5 Gy per fraction over 2 days were analysed retrospectively. Pre-treatment CT scans were used to assess the effect of catheter movement between fractions on implant quality, with and without movement correction. Implant quality was evaluated using dosimetric parameters. Results: Compared to the first fraction (f1) the mean inter-fraction caudal movement relative to the prostate base was 7.9 mm (f2) (range 0-21 mm) and 3.9 mm (f3) (range 0-25.5 mm). PTV D90% was reduced without movement correction by a mean of 27.8% (f2) and 32.3% (f3), compared with 5.3% and 5.1%, respectively, with catheter movement correction. Dose to 2 cc of the rectum increased by a mean of 0.69 (f2) and 0.76 Gy (f3) compared with an increase of 0.03 and 0.04 Gy, respectively, with correction. The urethra V12 also increased by a mean of 0.36 (f2) and 0.39 Gy (f3) compared with 0.06 and 0.16 Gy, respectively, with correction. Conclusions: Inter-fraction correction for catheter movement using pre-treatment imaging is critical to maintain the quality of an implant. Without movement correction there is significant risk of tumour under-dosage and normal tissue over-dosage. The findings of this study justify additional imaging between fractions in order to carry out correction.

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

International Nuclear Information System (INIS)

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

1998-01-01

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

High dose per fraction dosimetry of small fields with Gafchromic EBT2 film

International Nuclear Information System (INIS)

Hardcastle, Nicholas; Basavatia, Amar; Bayliss, Adam; Tome, Wolfgang A.

2011-01-01

Purpose: Small field dosimetry is prone to uncertainties due to the lack of electronic equilibrium and the use of the correct detector size relative to the field size measured. It also exhibits higher sensitivity to setup errors as well as large variation in output with field size and shape. Radiochromic film is an attractive method for reference dosimetry in small fields due to its ability to provide 2D dose measurements while having minimal impact on the dose distribution. Gafchromic EBT2 has a dose range of up to 40 Gy; therefore, it could potentially be useful for high dose reference dosimetry with high spatial resolution. This is a requirement in stereotactic radiosurgery deliveries, which deliver high doses per fraction to small targets. Methods: Targets of 4 mm and 12 mm diameters were treated to a minimum peripheral dose of 21 Gy prescribed to 80% of the maximum dose in one fraction. Target doses were measured with EBT2 film (both targets) and an ion chamber (12 mm target only). Measured doses were compared with planned dose distributions using profiles through the target and minimum peripheral dose coverage. Results: The measured target doses and isodose coverage agreed with the planned dose within ±1 standard deviation of three measurements, which were 2.13% and 2.5% for the 4 mm and 12 mm targets, respectively. Conclusions: EBT2 film is a feasible dosimeter for high dose per fraction reference 2D dosimetry.

IMRT dose fractionation for head and neck cancer: Variation in current approaches will make standardisation difficult

Energy Technology Data Exchange (ETDEWEB)

Ho, Kean F. (Academic Dept. of Radiation Oncology, Univ. of Manchester, Manchester (United Kingdom)); Fowler, Jack F. (Dept. of Human Oncology and Medical Physics, Univ. of Wisconsin, Wisconsin (United States)); Sykes, Andrew J.; Yap, Beng K.; Lee, Lip W.; Slevin, Nick J. (Dept. of Clinical Oncology, Christie Hospital NHS Foundation Trust, Manchester (United Kingdom))

2009-04-15

Introduction. Altered fractionation has demonstrated clinical benefits compared to the conventional 2 Gy/day standard of 70 Gy. When using synchronous chemotherapy, there is uncertainty about optimum fractionation. IMRT with its potential for Simultaneous Integrated Boost (SIB) adds further to this uncertainty. This survey will examine international practice of IMRT fractionation and suggest possible reasons for diversity in approach. Material and methods. Fourteen international cancer centres were surveyed for IMRT dose/fractionation practised in each centre. Results. Twelve different types of dose fractionation were reported. Conventional 70-72 Gy (daily 2 Gy/fraction) was used in 3/14 centres with concurrent chemotherapy while 11/14 centres used altered fractionation. Two centres used >1 schedule. Reported schedules and number of centres included 6 fractions/week DAHANCA regime (3), modest hypofractionation (=2.2 Gy/fraction) (3), dose-escalated hypofractionation (=2.3 Gy/fraction) (4), hyperfractionation (1), continuous acceleration (1) and concomitant boost (1). Reasons for dose fractionation variability include (i) dose escalation; (ii) total irradiated volume; (iii) number of target volumes; (iv) synchronous systemic treatment; (v) shorter overall treatment time; (vi) resources availability; (vii) longer time on treatment couch; (viii) variable GTV margins; (ix) confidence in treatment setup; (x) late tissue toxicity and (xi) use of lower neck anterior fields. Conclusions. This variability in IMRT fractionation makes any meaningful comparison of treatment results difficult. Some standardization is needed particularly for design of multi-centre randomized clinical trials.

Some thoughts on tolerance, dose, and fractionation in boron neutron capture therapy

International Nuclear Information System (INIS)

Gahbauer, R.; Goodman, J.; Blue, T.

1988-01-01

Unique to boron neutron capture therapy, the tolerance very strongly depends on the boron concentration in normal brain, skin and blood. If one first considers the ideal situation of a 2 KeV beam and a compound clearing from normal tissues and blood, the tolerance dose to epithermal beams relates to the maximum tolerated capture gamma dose and capture high LET dose, H (n,gamma)D and N(n,p) 14 C. The authors can relate this gamma and high LET dose to known clinical experience. Assuming gamma and high LET dose ratios as given by Fairchild and Bond, one may first choose a clearly safe high LET whole brain dose and calculate the unavoidably resulting gamma dose. To a first approximation 500 cGy of high LET dose results in 3,000 cGy gamma dose. One can speculate that this approximates the tolerance of whole brain to the 2 KeV beam with no contributing boron dose if the radiation is fractionated. It would clearly be beyond tolerance in a single fraction where most therapists would be uncomfortable to deliver even one third of the above doses

Acoustic neuromas: single dose vs fractionated therapy

International Nuclear Information System (INIS)

Fuss, M.; Debus, J.; Lohr, F.; Engenhart-Cabillic, R.; Wannenmacher, M.

1997-01-01

Purpose: Radiosurgical treatment (RS) of acoustic neuromas is a well established treatment. However, few data are available concerning conformal fractionated radiotherapy (FT) of this tumor entity. We evaluated treatment outcome and toxicity for both treatment modalities in 41 patients treated at our institution between 1984 and 1997. Material and Methods: All treatments were performed using a specially adapted linear accelerator and circular collimators for convergent beam RS or multi-leaf collimators (leaf thickness 1 or 3mm) for multi-field RS or fractionated treatment. 22 patients (7 male, 15 female, median age 60 years, range 20-83 years) were treated radiosurgically with single doses between 7 and 28 Gray (median 15 Gy) prescribed to the 80% isodose line. Tumor volumes ranged from 0.7 to 10.5 ccm with a median volume of 3.4 ccm. The median number of isocenters was 2 (1-4 isocenters). One patient was treated by a multi-field technique (14 isocentric irregularly shaped noncoplanar fields). 19 patients (5 male, 14 female, median age 55 years, range 20-81 years) were treated with stereotactic conformal radiotherapy. Median dose was 60 Gray with a median daily fraction size of 2 Gy and a median of 3 (1-4) irregularly shaped isocentric fields. Tumor volumes ranged from 0.7 to 32.4 ccm (median 15 ccm). Median follow-up was 30 months (7-149 months) for radiosurgical and 30 months (2-88 months) for fractionated treatment. Seven patients who underwent fractionated treatment had previously undergone neurosurgical resection on the contralateral side. One had undergone radiosurgery on the opposite side before. Results: All tumors were locally controlled. A volume reduction of more than 20% was seen in 16% after RS and 18% following FT. Typical posttherapeutic central reduction of contrast media enhancement was found in 73% following RS after a median of 8 (3-12) months and in 63% following FT after a median of 6 (1-12) months. Temporary brainstem edema was diagnosed in 4

Sterilization of boll weevil pupae with fractionated doses of gamma irradiation

International Nuclear Information System (INIS)

Haynes, J.W.; Mitlin, N.; Davich, T.B.; Dawson, J.R.; McGovern, W.L.; McKibben, G.H.

1977-01-01

Fractionated doses of 6,250-8,000 rads of gamma irradiation administered to pupae of the boll weevil, Anthonomus grandis Boh., sexually sterilized both sexes. Mortality of males thus treated with 6,250 and 8,000 rads via fractionation was 14% and 27% respectively, by 5 days posttreatment compared with 46% mortality when an equivalent acute dose was administered to newly emerged adults. Pheromone production of males irradiated at 6,250 rads was one-third that of the control for the first 4 days, but equal that of the control during 5-11 days posttreatment. This procedure lends itself to the large-scale sterilization of weevils needed in an eradication program. This technique is applicable to other insects that are highly susceptible to acute doses

Clinical applicability of biologically effective dose calculation for spinal cord in fractionated spine stereotactic body radiation therapy

International Nuclear Information System (INIS)

Lee, Seung Heon; Lee, Kyu Chan; Choi, Jinho; Ahn, So Hyun; Lee, Seok Ho; Sung, Ki Hoon; Kil, Se Hee

2015-01-01

The aim of the study was to investigate whether biologically effective dose (BED) based on linear-quadratic model can be used to estimate spinal cord tolerance dose in spine stereotactic body radiation therapy (SBRT) delivered in 4 or more fractions. Sixty-three metastatic spinal lesions in 47 patients were retrospectively evaluated. The most frequently prescribed dose was 36 Gy in 4 fractions. In planning, we tried to limit the maximum dose to the spinal cord or cauda equina less than 50% of prescription or 45 Gy 2/2 . BED was calculated using maximum point dose of spinal cord. Maximum spinal cord dose per fraction ranged from 2.6 to 6.0 Gy (median 4.3 Gy). Except 4 patients with 52.7, 56.4, 62.4, and 67.9 Gy 2/2 , equivalent total dose in 2-Gy fraction of the patients was not more than 50 Gy 2/2 (12.1–67.9, median 32.0). The ratio of maximum spinal cord dose to prescription dose increased up to 82.2% of prescription dose as epidural spinal cord compression grade increased. No patient developed grade 2 or higher radiation-induced spinal cord toxicity during follow-up period of 0.5 to 53.9 months. In fractionated spine SBRT, BED can be used to estimate spinal cord tolerance dose, provided that the dose per fraction to the spinal cord is moderate, e.g. < 6.0 Gy. It appears that a maximum dose of up to 45–50 Gy 2/2 to the spinal cord is tolerable in 4 or more fractionation regimen

Underprediction of human skin erythema at low doses per fraction by the linear quadratic model

International Nuclear Information System (INIS)

Hamilton, Christopher S.; Denham, James W.; O'Brien, Maree; Ostwald, Patricia; Kron, Tomas; Wright, Suzanne; Doerr, Wolfgang

1996-01-01

Background and purpose. The erythematous response of human skin to radiotherapy has proven useful for testing the predictions of the linear quadratic (LQ) model in terms of fractionation sensitivity and repair half time. No formal investigation of the response of human skin to doses less than 2 Gy per fraction has occurred. This study aims to test the validity of the LQ model for human skin at doses ranging from 0.4 to 5.2 Gy per fraction. Materials and methods. Complete erythema reaction profiles were obtained using reflectance spectrophotometry in two patient populations: 65 patients treated palliatively with 5, 10, 12 and 20 daily treatment fractions (varying thicknesses of bolus, various body sites) and 52 patients undergoing prostatic irradiation for localised carcinoma of the prostate (no bolus, 30-32 fractions). Results and conclusions. Gender, age, site and prior sun exposure influence pre- and post-treatment erythema values independently of dose administered. Out-of-field effects were also noted. The linear quadratic model significantly underpredicted peak erythema values at doses less than 1.5 Gy per fraction. This suggests that either the conventional linear quadratic model does not apply for low doses per fraction in human skin or that erythema is not exclusively initiated by radiation damage to the basal layer. The data are potentially explained by an induced repair model

Fractionated dose cholecystography: a comparison between iopanoic acid and sodium ipodate

Energy Technology Data Exchange (ETDEWEB)

Reiner, R.G.; Lawson, M.J.; Davies, G.T.; Tucker, W.G.; Mileski, O.; Read, T.R.; Grant, A.K. (Queen Elizabeth Hospital, Adelaide (Australia))

1980-11-01

Two randomised groups of 100 subjects each, undergoing oral cholecystography, were given either a 6 g fractionated dose of iopanoic acid (Telepaque) or sodium ipodate (Biloptin) to determine the relative merits of this dose schedule. Exclusions to the study were pregnancy and iodine sensitivity. Calculi or abnormal gall-bladder opacification were present in 45% of subjects. Both agents were equally effective in demonstrating abnormalities, although bile duct visualisation was better using iopanoic acid (P<0.05). Of 46 subjects with abnormal cholecystograms subsequently undergoing surgery, all had the diagnosis confirmed. Side effects occurred in 63% of all subjects, being twice as common in those taking iopanoic acid (P<0.01). Sodium ipodate in a large fractionated dose is favoured because of the lower occurrence of side effects without loss of diagnostic accuracy.

Fractionated dose cholecystography: a comparison between iopanoic acid and sodium ipodate

International Nuclear Information System (INIS)

Reiner, R.G.; Lawson, M.J.; Davies, G.T.; Tucker, W.G.; Mileski, O.; Read, T.R.; Grant, A.K.

1980-01-01

Two randomised groups of 100 subjects each, undergoing oral cholecystography, were given either a 6 g fractionated dose of iopanoic acid (Telepaque) or sodium ipodate (Biloptin) to determine the relative merits of this dose schedule. Exclusions to the study were pregnancy and iodine sensitivity. Calculi or abnormal gall-bladder opacification were present in 45% of subjects. Both agents were equally effective in demonstrating abnormalities, although bile duct visualisation was better using iopanoic acid (P<0.05). Of 46 subjects with abnormal cholecystograms subsequently undergoing surgery, all had the diagnosis confirmed. Side effects occurred in 63% of all subjects, being twice as common in those taking iopanoic acid (P<0.01). Sodium ipodate in a large fractionated dose is favoured because of the lower occurrence of side effects without loss of diagnostic accuracy. (author)

Improvements in dose calculation accuracy for small off-axis targets in high dose per fraction tomotherapy

Energy Technology Data Exchange (ETDEWEB)

Hardcastle, Nicholas; Bayliss, Adam; Wong, Jeannie Hsiu Ding; Rosenfeld, Anatoly B.; Tome, Wolfgang A. [Department of Human Oncology, University of Wisconsin-Madison, WI, 53792 (United States); Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, VIC 3002 (Australia) and Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia); Department of Human Oncology, University of Wisconsin-Madison, WI 53792 (United States); Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia) and Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur (Malaysia); Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia); Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53792 (United States); Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53792 (United States); Einstein Institute of Oncophysics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461 (United States) and Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia)

2012-08-15

Purpose: A recent field safety notice from TomoTherapy detailed the underdosing of small, off-axis targets when receiving high doses per fraction. This is due to angular undersampling in the dose calculation gantry angles. This study evaluates a correction method to reduce the underdosing, to be implemented in the current version (v4.1) of the TomoTherapy treatment planning software. Methods: The correction method, termed 'Super Sampling' involved the tripling of the number of gantry angles from which the dose is calculated during optimization and dose calculation. Radiochromic film was used to measure the dose to small targets at various off-axis distances receiving a minimum of 21 Gy in one fraction. Measurements were also performed for single small targets at the center of the Lucy phantom, using radiochromic film and the dose magnifying glass (DMG). Results: Without super sampling, the peak dose deficit increased from 0% to 18% for a 10 mm target and 0% to 30% for a 5 mm target as off-axis target distances increased from 0 to 16.5 cm. When super sampling was turned on, the dose deficit trend was removed and all peak doses were within 5% of the planned dose. For measurements in the Lucy phantom at 9.7 cm off-axis, the positional and dose magnitude accuracy using super sampling was verified using radiochromic film and the DMG. Conclusions: A correction method implemented in the TomoTherapy treatment planning system which triples the angular sampling of the gantry angles used during optimization and dose calculation removes the underdosing for targets as small as 5 mm diameter, up to 16.5 cm off-axis receiving up to 21 Gy.

Improvements in dose calculation accuracy for small off-axis targets in high dose per fraction tomotherapy

International Nuclear Information System (INIS)

Hardcastle, Nicholas; Bayliss, Adam; Wong, Jeannie Hsiu Ding; Rosenfeld, Anatoly B.; Tomé, Wolfgang A.

2012-01-01

Purpose: A recent field safety notice from TomoTherapy detailed the underdosing of small, off-axis targets when receiving high doses per fraction. This is due to angular undersampling in the dose calculation gantry angles. This study evaluates a correction method to reduce the underdosing, to be implemented in the current version (v4.1) of the TomoTherapy treatment planning software. Methods: The correction method, termed “Super Sampling” involved the tripling of the number of gantry angles from which the dose is calculated during optimization and dose calculation. Radiochromic film was used to measure the dose to small targets at various off-axis distances receiving a minimum of 21 Gy in one fraction. Measurements were also performed for single small targets at the center of the Lucy phantom, using radiochromic film and the dose magnifying glass (DMG). Results: Without super sampling, the peak dose deficit increased from 0% to 18% for a 10 mm target and 0% to 30% for a 5 mm target as off-axis target distances increased from 0 to 16.5 cm. When super sampling was turned on, the dose deficit trend was removed and all peak doses were within 5% of the planned dose. For measurements in the Lucy phantom at 9.7 cm off-axis, the positional and dose magnitude accuracy using super sampling was verified using radiochromic film and the DMG. Conclusions: A correction method implemented in the TomoTherapy treatment planning system which triples the angular sampling of the gantry angles used during optimization and dose calculation removes the underdosing for targets as small as 5 mm diameter, up to 16.5 cm off-axis receiving up to 21 Gy.

Dose rate effect from the relationship between ICRU rectal dose and local control rate in intracavitary radiotherapy for carcinoma of the uterine cervix. Six fraction HDR and three-fraction LDR in three weeks

International Nuclear Information System (INIS)

Jingu, Kenichi; Akita, Yuzou; Ohmagari, Jyunichi

2001-01-01

The dose rate effect, low dose rate radiotherapy (LDR)/high dose rate radiotherapy (HDR), was calculated using the isoeffect ICRU rectal dose by intracavitary radiotherapy (ICRT) for uterine cervix cancer. The subjects analyzed consisted of 78 LDR and 74 HDR patients whose ICRU rectal dose could be calculated and whose local control as stage II/III cases could be evaluated. The point A dose in ICRT was 45-55 Gy/3 fractions/3 weeks for LDR and 30 Gy/6 fractions/3 weeks for HDR. The dose effect relationships associated with local control at each whole pelvis external radiation dose were calculated using the double integration method and Probit analysis, and the 50% and 90% local control ICRU rectal doses were calculated from this relationship. Finally, the dose rate effect LDR/HDR was determined from 50% and 90% local control doses. The dose rate effect calculated from the 50% local control dose was 1.24 and that from the 90% local control dose was 1.14. (author)

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Radiation-induced rib fracture after stereotactic body radiotherapy with a total dose of 54-56 Gy given in 9-7 fractions for patients with peripheral lung tumor: impact of maximum dose and fraction size.

Science.gov (United States)

Aoki, Masahiko; Sato, Mariko; Hirose, Katsumi; Akimoto, Hiroyoshi; Kawaguchi, Hideo; Hatayama, Yoshiomi; Ono, Shuichi; Takai, Yoshihiro

2015-04-22

Radiation-induced rib fracture after stereotactic body radiotherapy (SBRT) for lung cancer has been recently reported. However, incidence of radiation-induced rib fracture after SBRT using moderate fraction sizes with a long-term follow-up time are not clarified. We examined incidence and risk factors of radiation-induced rib fracture after SBRT using moderate fraction sizes for the patients with peripherally located lung tumor. During 2003-2008, 41 patients with 42 lung tumors were treated with SBRT to 54-56 Gy in 9-7 fractions. The endpoint in the study was radiation-induced rib fracture detected by CT scan after the treatment. All ribs where the irradiated doses were more than 80% of prescribed dose were selected and contoured to build the dose-volume histograms (DVHs). Comparisons of the several factors obtained from the DVHs and the probabilities of rib fracture calculated by Kaplan-Meier method were performed in the study. Median follow-up time was 68 months. Among 75 contoured ribs, 23 rib fractures were observed in 34% of the patients during 16-48 months after SBRT, however, no patients complained of chest wall pain. The 4-year probabilities of rib fracture for maximum dose of ribs (Dmax) more than and less than 54 Gy were 47.7% and 12.9% (p = 0.0184), and for fraction size of 6, 7 and 8 Gy were 19.5%, 31.2% and 55.7% (p = 0.0458), respectively. Other factors, such as D2cc, mean dose of ribs, V10-55, age, sex, and planning target volume were not significantly different. The doses and fractionations used in this study resulted in no clinically significant rib fractures for this population, but that higher Dmax and dose per fraction treatments resulted in an increase in asymptomatic grade 1 rib fractures.

Impact of radiation technique, radiation fraction dose, and total cisplatin dose on hearing. Retrospective analysis of 29 medulloblastoma patients

International Nuclear Information System (INIS)

Scobioala, Sergiu; Kittel, Christopher; Ebrahimi, Fatemeh; Wolters, Heidi; Eich, Hans Theodor; Parfitt, Ross; Matulat, Peter; Am Zehnhoff-Dinnesen, Antoinette

2017-01-01

To analyze the incidence and degree of sensorineural hearing loss (SNHL) resulting from different radiation techniques, fractionation dose, mean cochlear radiation dose (D mean ), and total cisplatin dose. In all, 29 children with medulloblastoma (58 ears) with subclinical pretreatment hearing thresholds participated. Radiotherapy (RT) and cisplatin had been applied sequentially according to the HIT MED Guidance. Audiological outcomes up to the latest follow-up (median 2.6 years) were compared. Bilateral high-frequency SNHL was observed in 26 patients (90%). No significant differences were found in mean hearing threshold between left and right ears at any frequency. A significantly better audiological outcome (p < 0.05) was found after tomotherapy at the 6 kHz bone-conduction threshold (BCT) and left-sided 8 kHz air-conduction threshold (ACT) than after a combined radiotherapy technique (CT). Fraction dose was not found to have any impact on the incidence, degree, and time-to-onset of SNHL. Patients treated with CT had a greater risk of SNHL at high frequencies than tomotherapy patients even though D mean was similar. Increase in severity of SNHL was seen when the total cisplatin dose reached above 210 mg/m 2 , with the highest abnormal level found 8-12 months after RT regardless of radiation technique or fraction dose. The cochlear radiation dose should be kept as low as possible in patients who receive simultaneous cisplatin-based chemotherapy. The risk of clinically relevant HL was shown when D mean exceeds 45 Gy independent of radiation technique or radiation regime. Cisplatin ototoxicity was shown to have a dose-dependent effect on bilateral SNHL, which was more pronounced in higher frequencies. (orig.) [de

Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model

International Nuclear Information System (INIS)

Storb, R.; Raff, R.F.; Graham, T.; Appelbaum, F.R.; Deeg, H.J.; Schuening, F.G.; Shulman, H.; Pepe, M.

1993-01-01

The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing 60 Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionated total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs

Response of rat spinal cord to single and fractionated doses of accelerated heavy ions

International Nuclear Information System (INIS)

Leith, J.L.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Walton, R.E.; Woodruff, K.H.; Howard, J.

1980-01-01

The response of rat spinal cord to irradiation with accelerated heavy ions, in particular carbon and neon ions has been studied. Two different ionization regions in the modified Bragg curve for each ion have been studied for both single and fractionated exposures. We have defined the paralytic response as a function of dose and dose per fraction, and we have determined RBE and repair values. The response of rat spinal cord is both dose and LET dependent, which allows the derivation of RBE and repair values

Effects of intra-fraction motion on IMRT dose delivery: statistical analysis and simulation

International Nuclear Information System (INIS)

Bortfeld, Thomas; Jokivarsi, Kimmo; Goitein, Michael; Kung, Jong; Jiang, Steve B.

2002-01-01

There has been some concern that organ motion, especially intra-fraction organ motion due to breathing, can negate the potential merit of intensity-modulated radiotherapy (IMRT). We wanted to find out whether this concern is justified. Specifically, we wanted to investigate whether IMRT delivery techniques with moving parts, e.g., with a multileaf collimator (MLC), are particularly sensitive to organ motion due to the interplay between organ motion and leaf motion. We also wanted to know if, and by how much, fractionation of the treatment can reduce the effects. We performed a statistical analysis and calculated the expected dose values and dose variances for volume elements of organs that move during the delivery of the IMRT. We looked at the overall influence of organ motion during the course of a fractionated treatment. A linear-quadratic model was used to consider fractionation effects. Furthermore, we developed software to simulate motion effects for IMRT delivery with an MLC, with compensators, and with a scanning beam. For the simulation we assumed a sinusoidal motion in an isocentric plane. We found that the expected dose value is independent of the treatment technique. It is just a weighted average over the path of motion of the dose distribution without motion. If the treatment is delivered in several fractions, the distribution of the dose around the expected value is close to a Gaussian. For a typical treatment with 30 fractions, the standard deviation is generally within 1% of the expected value for MLC delivery if one assumes a typical motion amplitude of 5 mm (1 cm peak to peak). The standard deviation is generally even smaller for the compensator but bigger for scanning beam delivery. For the latter it can be reduced through multiple deliveries ('paintings') of the same field. In conclusion, the main effect of organ motion in IMRT is an averaging of the dose distribution without motion over the path of the motion. This is the same as for treatments

SU-E-T-480: Radiobiological Dose Comparison of Single Fraction SRS, Multi-Fraction SRT and Multi-Stage SRS of Large Target Volumes Using the Linear-Quadratic Formula

International Nuclear Information System (INIS)

Ding, C; Hrycushko, B; Jiang, S; Meyer, J; Timmerman, R

2014-01-01

Purpose: To compare the radiobiological effect on large tumors and surrounding normal tissues from single fraction SRS, multi-fractionated SRT, and multi-staged SRS treatment. Methods: An anthropomorphic head phantom with a centrally located large volume target (18.2 cm 3 ) was scanned using a 16 slice large bore CT simulator. Scans were imported to the Multiplan treatment planning system where a total prescription dose of 20Gy was used for a single, three staged and three fractionated treatment. Cyber Knife treatment plans were inversely optimized for the target volume to achieve at least 95% coverage of the prescription dose. For the multistage plan, the target was segmented into three subtargets having similar volume and shape. Staged plans for individual subtargets were generated based on a planning technique where the beam MUs of the original plan on the total target volume are changed by weighting the MUs based on projected beam lengths within each subtarget. Dose matrices for each plan were export in DICOM format and used to calculate equivalent dose distributions in 2Gy fractions using an alpha beta ratio of 10 for the target and 3 for normal tissue. Results: Singe fraction SRS, multi-stage plan and multi-fractionated SRT plans had an average 2Gy dose equivalent to the target of 62.89Gy, 37.91Gy and 33.68Gy, respectively. The normal tissue within 12Gy physical dose region had an average 2Gy dose equivalent of 29.55Gy, 16.08Gy and 13.93Gy, respectively. Conclusion: The single fraction SRS plan had the largest predicted biological effect for the target and the surrounding normal tissue. The multi-stage treatment provided for a more potent biologically effect on target compared to the multi-fraction SRT treatments with less biological normal tissue than single-fraction SRS treatment

Daily fraction dose recalculation based on rigid registration using Cone Beam CT

Directory of Open Access Journals (Sweden)

Courtney Bosse

2014-03-01

Full Text Available Purpose: To calculate the daily fraction dose for CBCT recalculations based on rigid registration and compare it to the planned CT doses.Methods: For this study, 30 patients that were previously treated (10 SBRT lung, 10 prostate and 10 abdomen were considered. The daily CBCT images were imported into the Pinnacle treatment planning system from Mosaic. Pinnacle was used to re-contour the regions of interest (ROI for the specific CBCT by copying the contours from the original CT plan, planned by the prescribing physician, onto each daily CBCT and then manually reshaping contours to match the ROIs. A new plan is then created with the re-contoured CBCT as primary image in order to calculate the daily dose delivered to each ROI. The DVH values are then exported into Excel and overlaid onto the original CT DVH to produce a graph.Results: For the SBRT lung patients, we found that there were small daily volume changes in the lungs, trachea and esophagus. For almost all regions of interest we found that the dose received each day was less than the predicted dose of the planned CT while the PTV dose was relatively the same each day. The results for the prostate patients were similar, showing slight differences in the DVH values for different days in the rectum and bladder but similar PTV.Conclusion: By comparing daily fraction dose between the re-contoured CBCT images and the original planned CT show that PTV coverage for both prostate and SBRT, it has been shown that for PTV coverage, a planned CT is adequate. However, there are differences between the dose for the organs surrounding the PTV. The dose difference is less than the planned in most instances.-----------------------Cite this article as: Bosse C, Tuohy R, Mavroidis P, Shi Z, Crownover R, Gutierrez A, Papanikolaou N, Stathakis S. Daily fraction dose recalculation based on rigid registration using Cone Beam CT. Int J Cancer Ther Oncol 2014; 2(2:020217. DOI: 10.14319/ijcto.0202.17

Optimization of the fractionated irradiation scheme considering physical doses to tumor and organ at risk based on dose–volume histograms

Energy Technology Data Exchange (ETDEWEB)

Sugano, Yasutaka [Graduate School of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan); Mizuta, Masahiro [Laboratory of Advanced Data Science, Information Initiative Center, Hokkaido University, Kita-11, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0811 (Japan); Takao, Seishin; Shirato, Hiroki; Sutherland, Kenneth L. [Department of Radiation Medicine, Graduate School of Medicine, Hokkaido University, Kita-15, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-8638 (Japan); Date, Hiroyuki, E-mail: date@hs.hokudai.ac.jp [Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan)

2015-11-15

Purpose: Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose–volume histograms for tumor and normal tissues of organs around the tumor. Methods: Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of the tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose–volume histogram. Results: It was found that the optimization of fractionation scheme incorporating the dose–volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8–32 fractions with a daily dose of 2.2–6.3 Gy. Conclusions: It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose–volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.

Preoperative chemoradiation for locally advanced rectal cancer: comparison of three radiation dose and fractionation schedules

International Nuclear Information System (INIS)

Park, Shin Hyung; Kim, Jae Chul

2016-01-01

The standard radiation dose for patients with locally rectal cancer treated with preoperative chemoradiotherapy is 45–50 Gy in 25–28 fractions. We aimed to assess whether a difference exists within this dose fractionation range. A retrospective analysis was performed to compare three dose fractionation schedules. Patients received 50 Gy in 25 fractions (group A), 50.4 Gy in 28 fractions (group B), or 45 Gy in 25 fractions (group C) to the whole pelvis, as well as concurrent 5-fluorouracil. Radical resection was scheduled for 8 weeks after concurrent chemoradiotherapy. Between September 2010 and August 2013, 175 patients were treated with preoperative chemoradiotherapy at our institution. Among those patients, 154 were eligible for analysis (55, 50, and 49 patients in groups A, B, and C, respectively). After the median follow-up period of 29 months (range, 5 to 48 months), no differences were found between the 3 groups regarding pathologic complete remission rate, tumor regression grade, treatment-related toxicity, 2-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, or overall survival. The circumferential resection margin width was a prognostic factor for 2-year locoregional recurrence-free survival, whereas ypN category was associated with distant metastasis-free survival, disease-free survival, and overall survival. High tumor regression grading score was correlated with 2-year distant metastasis-free survival and disease-free survival in univariate analysis. Three different radiation dose fractionation schedules, within the dose range recommended by the National Comprehensive Cancer Network, had no impact on pathologic tumor regression and early clinical outcome for locally advanced rectal cancer

Preoperative chemoradiation for locally advanced rectal cancer: comparison of three radiation dose and fractionation schedules

Energy Technology Data Exchange (ETDEWEB)

Park, Shin Hyung; Kim, Jae Chul [Dept. of Radiation Oncology, Kyungpook National University School of Medicine, Daegu (Korea, Republic of)

2016-06-15

The standard radiation dose for patients with locally rectal cancer treated with preoperative chemoradiotherapy is 45–50 Gy in 25–28 fractions. We aimed to assess whether a difference exists within this dose fractionation range. A retrospective analysis was performed to compare three dose fractionation schedules. Patients received 50 Gy in 25 fractions (group A), 50.4 Gy in 28 fractions (group B), or 45 Gy in 25 fractions (group C) to the whole pelvis, as well as concurrent 5-fluorouracil. Radical resection was scheduled for 8 weeks after concurrent chemoradiotherapy. Between September 2010 and August 2013, 175 patients were treated with preoperative chemoradiotherapy at our institution. Among those patients, 154 were eligible for analysis (55, 50, and 49 patients in groups A, B, and C, respectively). After the median follow-up period of 29 months (range, 5 to 48 months), no differences were found between the 3 groups regarding pathologic complete remission rate, tumor regression grade, treatment-related toxicity, 2-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, or overall survival. The circumferential resection margin width was a prognostic factor for 2-year locoregional recurrence-free survival, whereas ypN category was associated with distant metastasis-free survival, disease-free survival, and overall survival. High tumor regression grading score was correlated with 2-year distant metastasis-free survival and disease-free survival in univariate analysis. Three different radiation dose fractionation schedules, within the dose range recommended by the National Comprehensive Cancer Network, had no impact on pathologic tumor regression and early clinical outcome for locally advanced rectal cancer.

Not traditional regimes of radiotherapeutic dose fractionation as modifier of radiotherapy for carcinoma of lungs

International Nuclear Information System (INIS)

Artemova, N.A.

2008-01-01

The efficiency of applying various of radiotherapeutic dose fractionation was analyzed. The results of the own studies performed at the Scientific and Research Institute of Oncology and Medical Radiology for elaborating not traditional regimes of radiotherapeutic dose fractionation (a dynamic fractionation applying enlarged regimes at the first stage and the classic ones at the second stage) were presented. Appliance of the modified radiotherapy for the epidermoid carcinoma of the lungs allowed to increase the objective response from 45,3+-3% to 80+-5% the tumor disappearing completely in 40+-6% of patients as compared with 10+-2%. Appliance of the intensive not traditional variant of the radiotherapy dynamic fractionation in case of a small cell carcinoma of the lungs resulted in the therapy duration reduction from 6 to 4 weeks. Thus the not traditional dose fractionation might become a mechanism for the improving the radiotherapy of persons suffering from the carcinoma of the lungs. (authors)

Critical dose and toxicity index of organs at risk in radiotherapy: Analyzing the calculated effects of modified dose fractionation in non–small cell lung cancer

Energy Technology Data Exchange (ETDEWEB)

Pedicini, Piernicola, E-mail: ppiern@libero.it [Service of Medical Physics, I.R.C.C.S. Regional Cancer Hospital C.R.O.B, Rionero in Vulture (Italy); Strigari, Lidia [Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome (Italy); Benassi, Marcello [Service of Medical Physics, Scientific Institute of Tumours of Romagna I.R.S.T., Meldola (Italy); Caivano, Rocchina [Service of Medical Physics, I.R.C.C.S. Regional Cancer Hospital C.R.O.B, Rionero in Vulture (Italy); Fiorentino, Alba [U.O. of Radiotherapy, I.R.C.C.S. Regional Cancer Hospital C.R.O.B., Rionero in Vulture (Italy); Nappi, Antonio [U.O. of Nuclear Medicine, I.R.C.C.S. Regional Cancer Hospital C.R.O.B., Rionero in Vulture (Italy); Salvatore, Marco [U.O. of Nuclear Medicine, I.R.C.C.S. SDN Foundation, Naples (Italy); Storto, Giovanni [U.O. of Nuclear Medicine, I.R.C.C.S. Regional Cancer Hospital C.R.O.B., Rionero in Vulture (Italy)

2014-04-01

To increase the efficacy of radiotherapy for non–small cell lung cancer (NSCLC), many schemes of dose fractionation were assessed by a new “toxicity index” (I), which allows one to choose the fractionation schedules that produce less toxic treatments. Thirty-two patients affected by non resectable NSCLC were treated by standard 3-dimensional conformal radiotherapy (3DCRT) with a strategy of limited treated volume. Computed tomography datasets were employed to re plan by simultaneous integrated boost intensity-modulated radiotherapy (IMRT). The dose distributions from plans were used to test various schemes of dose fractionation, in 3DCRT as well as in IMRT, by transforming the dose-volume histogram (DVH) into a biological equivalent DVH (BDVH) and by varying the overall treatment time. The BDVHs were obtained through the toxicity index, which was defined for each of the organs at risk (OAR) by a linear quadratic model keeping an equivalent radiobiological effect on the target volume. The less toxic fractionation consisted in a severe/moderate hyper fractionation for the volume including the primary tumor and lymph nodes, followed by a hypofractionation for the reduced volume of the primary tumor. The 3DCRT and IMRT resulted, respectively, in 4.7% and 4.3% of dose sparing for the spinal cord, without significant changes for the combined-lungs toxicity (p < 0.001). Schedules with reduced overall treatment time (accelerated fractionations) led to a 12.5% dose sparing for the spinal cord (7.5% in IMRT), 8.3% dose sparing for V{sub 20} in the combined lungs (5.5% in IMRT), and also significant dose sparing for all the other OARs (p < 0.001). The toxicity index allows to choose fractionation schedules with reduced toxicity for all the OARs and equivalent radiobiological effect for the tumor in 3DCRT, as well as in IMRT, treatments of NSCLC.

Lack of evidence for increased tolerance of rat spinal cord with decreasing fraction doses below 2 Gy

International Nuclear Information System (INIS)

Ang, K.K.; van der Kogel, A.J.; van der Schueren, E.

1985-01-01

The radiation tolerance of the spinal cord, both in man and in rats, has been shown to depend strongly on the size of the dose per fraction. With fraction doses down to about 2 Gy, the spinal cord tolerance can be predicted by a modified Ellis formula. More recently alternative isoeffect formulas were based on the linear-quadratic (LQ) model of cell survival where the effect of dose fractionation is characterized by the ratio α/β which varies from tissue to tissue. For the spinal cord, as well as for other late responding tissues, the ratio α/β is small, in contrast to most acutely responding tissues. Both the Ellis-type formula, and to a lesser extent the LQ-model, predict a continuously increasing tolerance dose with decreasing fraction size. From previous experiments on the rat cervical spinal cord with doses per fraction down to about 2 Gy, the ratio α/β was determined to be 1.7 Gy, and the LQ-model would predict a rise in tolerance with a reduction in fraction size to far below 2 Gy. Based on these predictions clinical studies have been initiated assuming a significantly increased tolerance by reduction of fraction size to about 1 Gy. However, in the present experiments no evidence was found for such an increase in tolerance with fraction sizes below 2 Gy

Immunogenicity to poliovirus type 2 following two doses of fractional intradermal inactivated poliovirus vaccine: A novel dose sparing immunization schedule.

Science.gov (United States)

Anand, Abhijeet; Molodecky, Natalie A; Pallansch, Mark A; Sutter, Roland W

2017-05-19

The polio eradication endgame strategic plan calls for the sequential removal of Sabin poliovirus serotypes from the trivalent oral poliovirus vaccine (tOPV), starting with type 2, and the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV), to maintain an immunity base against poliovirus type 2. The global removal of oral poliovirus type 2 was successfully implemented in May 2016. However, IPV supply constraints has prevented introduction in 21 countries and led to complete stock-out in >20 countries. We conducted a literature review and contacted corresponding authors of recent studies with fractional-dose IPV (fIPV), one-fifth of intramuscular dose administered intradermally, to conduct additional type 2 immunogenicity analyses of two fIPV doses compared with one full-dose IPV. Four studies were identified that assessed immunogenicity of two fIPV doses compared to one full-dose IPV. Two fractional doses are more immunogenic than 1 full-dose, with type 2 seroconversion rates improving between absolute 19-42% (median: 37%, pvaccine compared to one full-dose IPV. In response to the current IPV shortage, a schedule of two fIPV doses at ages 6 and 14weekshas been endorsed by technical oversight committees and has been introduced in some affected countries. Copyright © 2017. Published by Elsevier Ltd.

Prooxidate - antioxidate homeostasis in guinea pigs after fractional low-dose irradiation

International Nuclear Information System (INIS)

Baraboj, V.A.; Olyijnik, S.A.; Khmelevs'kij, Yi.V.

1993-01-01

We studied the influence of fractional total irradiation in the total dose of 1 Gy on the amount of lipids peroxide oxidation (LPO) products and ascorbic acid in the spleen, intestine and brain of guinea-pigs. The obtained date suggest that it is advisable to use ascorbic acid to correct postirradiation changes in the organism exposed to small doses of ionizing radiation

Radiation-induced rib fracture after stereotactic body radiotherapy with a total dose of 54–56 Gy given in 9–7 fractions for patients with peripheral lung tumor: impact of maximum dose and fraction size

International Nuclear Information System (INIS)

Aoki, Masahiko; Sato, Mariko; Hirose, Katsumi; Akimoto, Hiroyoshi; Kawaguchi, Hideo; Hatayama, Yoshiomi; Ono, Shuichi; Takai, Yoshihiro

2015-01-01

Radiation-induced rib fracture after stereotactic body radiotherapy (SBRT) for lung cancer has been recently reported. However, incidence of radiation-induced rib fracture after SBRT using moderate fraction sizes with a long-term follow-up time are not clarified. We examined incidence and risk factors of radiation-induced rib fracture after SBRT using moderate fraction sizes for the patients with peripherally located lung tumor. During 2003–2008, 41 patients with 42 lung tumors were treated with SBRT to 54–56 Gy in 9–7 fractions. The endpoint in the study was radiation-induced rib fracture detected by CT scan after the treatment. All ribs where the irradiated doses were more than 80% of prescribed dose were selected and contoured to build the dose-volume histograms (DVHs). Comparisons of the several factors obtained from the DVHs and the probabilities of rib fracture calculated by Kaplan-Meier method were performed in the study. Median follow-up time was 68 months. Among 75 contoured ribs, 23 rib fractures were observed in 34% of the patients during 16–48 months after SBRT, however, no patients complained of chest wall pain. The 4-year probabilities of rib fracture for maximum dose of ribs (Dmax) more than and less than 54 Gy were 47.7% and 12.9% (p = 0.0184), and for fraction size of 6, 7 and 8 Gy were 19.5%, 31.2% and 55.7% (p = 0.0458), respectively. Other factors, such as D2cc, mean dose of ribs, V10–55, age, sex, and planning target volume were not significantly different. The doses and fractionations used in this study resulted in no clinically significant rib fractures for this population, but that higher Dmax and dose per fraction treatments resulted in an increase in asymptomatic grade 1 rib fractures

Dose fractionation in synchrotron radiation x-ray phase micro-tomography

International Nuclear Information System (INIS)

Frachon, Thibaut; Weber, Loriane; Hesse, Bernhard; Rit, Simon; Dong, Pei; Olivier, Cecile; Peyrin, Françoise; Langer, Max

2015-01-01

Phase sensitive x-ray imaging expands the applicability of standard attenuation based techniques by offering several orders of magnitude of increase in sensitivity. Due to the short wavelength, x-ray phase is not directly measurable, but has to be put in evidence by the use of phase contrast techniques. The phase can then be reconstructed from one or several phase contrast images. In this study, we consider synchrotron x-ray phase micro-computed tomography (μCT) based on free space propagation for heterogeneous and strongly absorbing objects. This technique generally relies on acquiring several scans of the sample at different detector distances. It is also generally believed that multi-distance phase μCT needs a higher dose input than single distance phase μCT. The purpose of this work is to study the impact of different means of dose fractionation on the reconstructed image quality. We define different acquistion schemes in multi-distance in-line phase μCT. Previously, the exposure time at each sample-to-detector distance was usually kept the same. Here, we let not only the number of distances vary but also the fraction of exposure time at each distance, the total exposure time being kept constant. Phase retrieval is performed with the mixed approach algorithm. The reconstructed μCT images are compared in terms of accuracy, precision and resolution. In addition, we also compare the result of dose fractionated multi distance phase μCT to single distance phase μCT using the same total radiation dose. In the multi-distance approach, we find that using different exposure times on each distance improves the image quality in the reconstructed image. Further, we show that, despite having the same total dose delivery, the multi distance imaging method gives better image quality than the single distance method, at the cost of an additional overhead from camera displacements and reference images. We show that by optimizing the acquistion parameters in terms of

Implications of the quadratic cell survival curve and human skin radiation ''tolerance doses'' on fractionation and superfractionation dose selection

International Nuclear Information System (INIS)

Douglas, B.G.

1982-01-01

An analysis of early published multifraction orthovoltage human acute skin irradiation tolerance isoeffect doses is presented. It indicates that human acute skin radiation reactions may result from the repetition, with each dose fraction, of a cell survival curve of the form: S = e/sup -(αD + βD 2 )/). The analysis also shows no need for an independent proliferation related time factor for skin, for daily treatments of six weeks or less in duration. The value obtained for the constant β/α for orthovoltage irradiation from these data is 2.9 x 10 -3 rad -1 for the cell line determining acute skin tolerance. A radiation isoeffect relationship, based on the quadratic cell survival curve, is introduced for human skin. This relationship has some advantages over the nominal standard dose (NSD). First, its use is not restricted to tolerance level reactions. Second, a modification of the relationship, which is also introduced, may be employed in the selection of doses per treatment when irradiation dose fractions are administered at short intervals where repair of sublethal injury is incomplete

Radiation-induced rectal complications are not influenced by age: a dose fractionation study in the rat.

Science.gov (United States)

van den Aardweg, Gerard J M J; Olofsen-van Acht, Manouk J J; van Hooije, Christel M C; Levendag, Peter C

2003-05-01

Radiation-induced complications of the rectum are an important dose-limiting factor in radiotherapy of pelvic malignancies. In general, animal studies demonstrated no differences in acute and late normal tissue toxicity with age, but little is known about rectal complications in relation to age. For this purpose, an extensive histological and dose fractionation study was carried out on the rectum of young (12 weeks) and older (77-80 weeks) rats. In this paper, the results of dose fractionation are presented in relation to age at the time of irradiation. Young and older animals were irradiated with single and fractionated doses. After irradiation, rectal complications could lead to occlusion and stenosis, eventually resulting in the clinical symptoms of a megacolon and a possible fistula. For each dose group, cumulative survival rates were obtained with Kaplan-Meier analysis, from which dose-effect curves and the associated LD(50) values for a megacolon/fistula were calculated. The majority of responders died between 8 and 24 weeks after irradiation, irrespective of age. For both age groups, only the fractionation data showed a reduction in the mean latency with increasing dose. In the older age group, 39% of the responders developed a fistula compared to 26% for the younger animals. The LD(50) values increased from around 30 Gy after single doses to nearly 65 Gy after 10 fractions. The increases in LD(50) values with the number of fractions were independent of the age of the rats. For each of the dose fractionation schedules, log-rank testing indicated no significant differences in cumulative survival rates between younger and older animals (P > 0.10). The high alpha/beta ratios obtained for both the young and older animals strongly suggested that the late rectal complications were a consequence of early epithelial injury. Associated histological findings indicated that blood vessel damage, which was already evident at a high incidence at 4 weeks after irradiation

Fractionation in normal tissues: the (α/β)eff concept can account for dose heterogeneity and volume effects.

Science.gov (United States)

Hoffmann, Aswin L; Nahum, Alan E

2013-10-07

The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely used in external-beam radiotherapy to derive a new tumour dose prescription such that there is normal-tissue (NT) iso-effect when changing the fraction size and/or number. However, as conventionally applied, the WIF is invalid unless the normal-tissue response is solely determined by the tumour dose. We propose a generalized WIF (gWIF) which retains the tumour prescription dose, but replaces the intrinsic fractionation sensitivity measure (α/β) by a new concept, the normal-tissue effective fractionation sensitivity, [Formula: see text], which takes into account both the dose heterogeneity in, and the volume effect of, the late-responding normal-tissue in question. Closed-form analytical expressions for [Formula: see text] ensuring exact normal-tissue iso-effect are derived for: (i) uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose distributions and arbitrary n, a numerical solution for [Formula: see text] exhibits a weak dependence on the number of fractions. As n is increased, [Formula: see text] increases from its intrinsic value at n = 0 (100% serial normal-tissue) to values close to or even exceeding the tumour (α/β) at n = 1 (100% parallel normal-tissue), with the highest values of [Formula: see text] corresponding to the most conformal dose distributions. Applications of this new concept to inverse planning and to highly conformal modalities are discussed, as is the effect of possible deviations from LQ behaviour at large fraction sizes.

Responses of rat R-1 cells to low dose rate gamma radiation and multiple daily dose fractions

International Nuclear Information System (INIS)

Kal, H.B.; Bijman, J.Th.

1981-01-01

Multifraction irradiation may offer the same therapeutic gain as continuous irradiation. Therefore, a comparison of the efficacy of low dose rate irradiation and multifraction irradiation was the main objective of the experiments to be described. Both regimens were tested on rat rhabdomyosarcoma (R-1) cells in vitro and in vivo. Exponentially growing R-1 cells were treated in vitro by a multifraction irradiation procedure with dose fractions of 2 Gy gamma radiation and time intervals of 1 to 3 h. The dose rate was 1.3 Gy.min -1 . The results indicate that multifractionation of the total dose is more effective with respect to cell inactivation than continuous irradiation. (Auth.)

The NARLAL2 dose escalation trial: dosimetric implications of inter-fractional changes in organs at risk

DEFF Research Database (Denmark)

Hoffmann, Lone; Knap, Marianne Marquard; Khalil, Azza Ahmed

2018-01-01

and an escalated treatment plan. In the escalated arm, mean doses up to 95 Gy/33 fractions (tumour) and 74 Gy/33 fractions (lymph nodes) are delivered to the most 18fluorodeoxyglucose-positron emission tomography (18FDG PET) active regions. The dose distributions are limited by strict constraints to OARs...

Response of rat spinal cord to single and fractionated doses of accelerated heavy ions

International Nuclear Information System (INIS)

Leith, J.T.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Howard, J.

1982-01-01

The thoraco-lumbar (T12-L1) region of the spinal cord of rats was exposed to either single or fractionated (four daily exposures) doses of X rays (230 kVp) or heavy ions. The heavy ions used were carbon and neon, and the relative biological effectiveness (RBE) of both the plateau ionization region and the midpeak region of 4-cm spread-out Bragg peaks of each heavy ion were investigated. For single doses of carbon and neon ions in the plateau ionization region, RBE values of 1.45 +/- 0.25 (propagated 95% confidence limits) and 1.46 +/- 0.33, respectively, were obtained. In the spread peak regions for carbon and neon ions, the RBE values were 1.48 +/- 0.18 and 1.86 +/- 0.42, respectively. These values were obtained using the dose needed to produce 50% paralysis in a group of irradiated rats as the isoeffect comparison dose (ED 50 dose). Similarly, in groups of rats receiving four daily exposures, the RBE values for carbon and neon ions in the plateau ionization region were 1.31 +/- 0.27 and 1.80 +/- 0.24, respectively. In the spread peak regions of ionization for carbon and neon ions, the RBE values were 1.95 +/- 0.19 and 2.18 +/- 0.23, respectively. Similar values for RBE were obtained using changes in the activity of enzymes in spinal cord tissue (cyclic nucleotide phosphohydrolase and γ-glutamyl transpeptidase). Also, it was estimated that, for X irradiation, the fractional amount of dose repaired (at the ED 50 dose) was 0.64 +/- 0.10 (95% confidence limits). For carbon and neon ions in the plateau ionization region, the values for the fractional amount of dose repaired were 0.70 +/- 0.27 and 0.48 +/- 0.20, and for carbon and neon ions in the spread peak region of ionization, the fractional repair values were 0.40 +/- 0.10 and 0.52 +/- 0.17. Spinal cord tissue therefore shows a high capacity for subeffective damage repair

Effects of local single and fractionated X-ray doses on rat bone marrow blood flow and red blood cell volume

International Nuclear Information System (INIS)

Pitkaenen, M.A.; Hopewell, J.W.

1985-01-01

Time and dose dependent changes in blood flow and red blood cell volume were studied in the locally irradiated bone marrow of the rat femur after single and fractionated doses of X-rays. With the single dose of 10 Gy the bone marrow blood flow although initially reduced returned to the control levels by seven months after irradiation. With doses >=15 Gy the blood flow was still significantly reduced at seven months. The total dose levels predicted by the nominal standard dose equation for treatments in three, six or nine fractions produced approximately the same degree of reduction in the bone marrow blood flow seven months after the irradiation. However, the fall in the red blood cell volume was from 23 to 37% greater in the three fractions groups compared with that in the nine fractions groups. Using the red blood cell volume as a parameter the nominal standard dose formula underestimated the severity of radiation damage in rat bone marrow at seven months for irradiation with small numbers of large dose fractions. (orig.) [de

Insect radiosensitivity: dose curves and dose-fractionation studies of dominant lethal mutations in the mature sperm of 4 insect species

International Nuclear Information System (INIS)

LaChance, L.E.; Graham, C.K.

1984-01-01

Males of 4 species of insects: Musca domestica L. (housefly) (Diptera), Oncopeltus fasciatus (Dallas) (milkweed bug) (Hemiptera), Anagasta kuhniella (Zeller) (mealmoth) (Lepidoptera) and Heliothis virescens (Fab.) (tobacco budworm) (Lepidoptera) were irradiated as adults. Dose-response curves for the induction of dominant lethal mutations in the mature sperm were constructed. The curves were analyzed mathematically and compared with theoretical computer simulated curves requiring 1, 2, 4, 8 and 16 'hits' for the induction of a dominant lethal mutation. The 4 species belonging to 3 different orders of insects showed a wide range in radiation sensitivity and vastly different dose-response curves. When the data were analyzed by several mathematical models the authors found that a logistic response curve gave reasonably good fit with vastly different parameters for the 4 species. Dose-fractionation experiments showed no reduction in the frequency of lethal mutations induced in any species when an acute dose was fractionated into 2 equal exposures separated by an 8-h period. (Auth.)

Inter fraction variations in rectum and bladder volumes and dose distributions during high dose rate brachytherapy treatment of the uterine cervix investigated by repetitive CT-examinations

International Nuclear Information System (INIS)

Hellebust, Taran Paulsen; Dale, Einar; Skjoensberg, Ane; Olsen, Dag Rune

2001-01-01

Purpose: To evaluate variation of dose to organs at risk for patients receiving fractionated high dose rate gynaecological brachytherapy by using CT-based 3D treatment planning and dose-volume histograms (DVH). Materials and methods: Fourteen patients with cancer of the uterine cervix underwent three to six CT examinations (mean 4.9) during their course of high-dose-rate brachytherapy using radiographically compatible applicators. The rectal and bladder walls were delineated and DVHs were calculated. Results: Inter fraction variation of the bladder volume (CV mean =44.1%) was significantly larger than the inter fraction variation of the mean dose (CV mean =19.9%, P=0.005) and the maximum dose (CV mean =17.5%, P=0.003) of the bladder wall. The same trend was seen for rectum, although the figures were not significantly different. Performing CT examinations at four of seven brachytherapy fractions reduced the uncertainty to 4 and 7% for the bladder and rectal doses, respectively. A linear regression analysis showed a significant, negative relationship between time after treatment start and the whole bladder volume (P=0.018), whereas no correlation was found for the rectum. For both rectum and bladder a linear regression analysis revealed a significant, negative relationship between the whole volume and median dose (P<0.05). Conclusion: Preferably a CT examination should be provided at every fraction. However, this is logistically unfeasible in most institutions. To obtain reliable DVHs the patients will in the future undergo 3-4 CT examinations during the course of brachytherapy at our institution. Since this study showed an association between large bladder volumes and dose reductions, the patients will be treated with a standardized bladder volume

Effect of single dose, fractionated, and hyperfractionated trunk irradiation on weight gain, respiration frequency, and survival in rats

International Nuclear Information System (INIS)

Kimler, B.F.; Giri, P.G.S.; Giri, U.P.; Cox, G.G.

1986-01-01

It is concluded that, in this rat trunk irradiation model, fractionation of a single dose into two equal doses separated by 4-6 h produced a sparing effect of approx. 5Gy as measured by delay in weight gain; approx. 4Gy as measured by increased respiration frequency; and approx. 6Gy as measured by survival. Fractionation into daily doses or hyperfractionation into twice-daily doses permitted an approximate doubling of the dose required for the same suppression of weight gain. For the respiration rates and survival endpoints, fractionation or hyperfractionation produced an even greater sparing effect since there was no increase in the respiration frequency at twice the doses that would produce changes if delivered within a few hours; and since essentially no lethality was observed at twice the doses that would kill 70%-100% of animals if delivered in one day. (UK)

Comparison of Different Fractionation Schedules Toward a Single Fraction in High-Dose-Rate Brachytherapy as Monotherapy for Low-Risk Prostate Cancer Using 3-Dimensional Radiobiological Models

Energy Technology Data Exchange (ETDEWEB)

Mavroidis, Panayiotis, E-mail: mavroidis@uthscsa.edu [Department of Radiation Oncology, University of Texas Health Sciences Center, San Antonio, Texas (United States); Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Stockholm (Sweden); Milickovic, Natasa [Department of Medical Physics and Engineering, Strahlenklinik, Klinikum Offenbach GmbH, Offenbach (Germany); Cruz, Wilbert F. [Department of Radiation Oncology, University of Texas Health Sciences Center, San Antonio, Texas (United States); Tselis, Nikolaos [Strahlenklinik, Klinikum Offenbach GmbH, Offenbach (Germany); Karabis, Andreas [Pi-Medical Ltd., Athens (Greece); Stathakis, Sotirios; Papanikolaou, Nikos [Department of Radiation Oncology, University of Texas Health Sciences Center, San Antonio, Texas (United States); Zamboglou, Nikolaos [Strahlenklinik, Klinikum Offenbach GmbH, Offenbach (Germany); Baltas, Dimos [Department of Medical Physics and Engineering, Strahlenklinik, Klinikum Offenbach GmbH, Offenbach (Germany); Nuclear and Particle Physics Section, Physics Department, University of Athens, Athens (Greece)

2014-01-01

Purpose: The aim of the present study was the investigation of different fractionation schemes to estimate their clinical impact. For this purpose, widely applied radiobiological models and dosimetric measures were used to associate their results with clinical findings. Methods and Materials: The dose distributions of 12 clinical high-dose-rate brachytherapy implants for prostate were evaluated in relation to different fractionation schemes. The fractionation schemes compared were: (1) 1 fraction of 20 Gy; (2) 2 fractions of 14 Gy; (3) 3 fractions of 11 Gy; and (4) 4 fractions of 9.5 Gy. The clinical effectiveness of the different fractionation schemes was estimated through the complication-free tumor control probability (P{sub +}), the biologically effective uniform dose, and the generalized equivalent uniform dose index. Results: For the different fractionation schemes, the tumor control probabilities were 98.5% in 1 × 20 Gy, 98.6% in 2 × 14 Gy, 97.5% in 3 × 11 Gy, and 97.8% in 4 × 9.5 Gy. The corresponding P{sub +} values were 88.8% in 1 × 20 Gy, 83.9% in 2 × 14 Gy, 86.0% in 3 × 11 Gy, and 82.3% in 4 × 9.5 Gy. With use of the fractionation scheme 4 × 9.5 Gy as reference, the isoeffective schemes regarding tumor control for 1, 2, and 3 fractions were 1 × 19.68 Gy, 2 × 13.75 Gy, and 3 × 11.05 Gy. The optimum fractionation schemes for 1, 2, 3, and 4 fractions were 1 × 19.16 Gy with a P{sub +} of 91.8%, 2 × 13.2 Gy with a P{sub +} of 89.6%, 3 × 10.6 Gy with a P{sub +} of 88.4%, and 4 × 9.02 Gy with a P{sub +} of 86.9%. Conclusions: Among the fractionation schemes 1 × 20 Gy, 2 × 14 Gy, 3 × 11 Gy, and 4 × 9.5 Gy, the first scheme was more effective in terms of P{sub +}. After performance of a radiobiological optimization, it was shown that a single fraction of 19.2 to 19.7 Gy (average 19.5 Gy) should produce at least the same benefit as that given by the 4 × 9.5 Gy scheme, and it should reduce the expected total complication probability by

Single-dose and fractionated irradiation of four human lung cancer cell lines in vitro

International Nuclear Information System (INIS)

Brodin, O.; Lennartsson, L.; Nilsson, S.

1991-01-01

Four established human lung cancer cell lines were exposed to single-dose irradiation. The survival curves of 2 small cell lung carcinomas (SCLC) were characterized by a limited capacity for repair with small and moderate shoulders with extrapolation numbers (n) of 1.05 and 1.60 respectively. Two non-small cell lung carcinoma (NSCLC) cell lines, one squamous cell (SQCLC) and one large cell (LCLC) had large shoulders with n-values of 73 and 15 respectively. The radiosensitivity when measured as D 0 did not, however, differ as much from cell line to cell line, with values from 1.22 to 1.65. The surviving fraction after 2 Gy (SF2) was 0.24 and 0.42 respectively in the SCLC cell lines and 0.90 and 0.88 respectively in the NSCLC cell lines. Fractionated irradiation delivered according to 3 different schedules was also investigated. All the schedules delivered a total dose of 10 Gy in 5 days and were applied in 1, 2 and 5 Gy dose fractions respectively. Survival followed the pattern found after single-dose irradiation; it was lowest in the SCLC cell line with the lowest SF and highest in the two NSCLC cell lines. In the SCLC cell lines all schedules were approximately equally efficient. In the LCLC and in the SQCLC cell lines, the 5 Gy schedule killed more cells than the 1 and 2 Gy schedules. The results indicate that the size of the shoulder of the survival curve is essential when choosing the most tumoricidal fractionation schedule. (orig.)

Cell kinetic changes in the follicular epithelium of pig skin after irradiation with single and fractionated doses of X rays

International Nuclear Information System (INIS)

Morris, G.M.; Hopewell, J.W.

1989-01-01

Changes in cell kinetics of the follicular epithelium of the pig were studied after x-irradiation with single and fractionated doses (30 fractions/39 days) and compared with previous epidermal data. In the follicular epithelium there was an initial degenerative phase, when the rate of cell depletion was independent of radiation dose and mode of administration. Repopulation was seen between the 14th and 18th days after single doses (15 or 20 Gy) and by the 28th day after the start of irradiation with fractionated doses (52.3-80.0 Gy). The degree of cell depletion and subsequent rate of repopulation were independent of dose. The regenerative phase was characterized by an increased cell proliferation. Islands of cells with appearance similar to cells in the normal follicular epithelium, were seen 18 days after a single dose of 20 Gy and 42 days after the start of fractionated irradiation. Compared with the epidermis, the follicular epithelium exhibited considerably less evidence of damage after both single and fractionated doses. There was a lower incidence of degenerate cells and reduced levels of cell depletion in the follicular epithelium. (author)

A generalised formulation of the 'incomplete-repair' model for cell survival and tissue response to fractionated low dose-rate irradiation

International Nuclear Information System (INIS)

Nilsson, P.; Joiner, M.C.

1990-01-01

A generalized equation for cell survival or tissue effects after fractionated low dose-rate irradiations, when there is incomplete repair between fractions and significant repair during fractions, is derived in terms of the h- and g-functions of the 'incomplete-repair' (IR) model. The model is critically dependent on α/β, repair half-time, treatment time and interfraction interval, and should therefore be regarded primarily as a tool for the analysis of fractionation and dose-rate effects in carefully designed radiobiological experiments, although it should also be useful in exploring, in a general way, the feasibility of clinical treatment protocols using fractionated low dose-rate treatments. (author)

Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery

International Nuclear Information System (INIS)

Moussazadeh, Nelson; Lis, Eric; Katsoulakis, Evangelia; Kahn, Sweena; Svoboda, Marek; DiStefano, Natalie M.; McLaughlin, Lily; Bilsky, Mark H.; Yamada, Yoshiya; Laufer, Ilya

2015-01-01

Purpose: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. Methods and Materials: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. Results: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen

Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery

Energy Technology Data Exchange (ETDEWEB)

Moussazadeh, Nelson [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York (United States); Lis, Eric [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Katsoulakis, Evangelia [Department of Radiation Oncology, New York Methodist Hospital, Brooklyn, New York (United States); Kahn, Sweena; Svoboda, Marek; DiStefano, Natalie M.; McLaughlin, Lily [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Bilsky, Mark H. [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York (United States); Yamada, Yoshiya [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Laufer, Ilya, E-mail: lauferi@mskcc.org [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York (United States)

2015-10-01

Purpose: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. Methods and Materials: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. Results: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen

Effects of dose, dose-rate and fraction on radiation-induced breast and lung cancers

International Nuclear Information System (INIS)

Howe, G.R.

1992-01-01

Recent results from a large Canadian epidemiologic cohort study of low-LET radiation and cancer will be described. This is a study of 64,172 tuberculosis patients first treated in Canada between 1930 and 1952, of whom many received substantial doses to breast and lung tissue from repeated chest fluoroscopies. The mortality of the cohort between 1950 and 1987 has been determined by computerized record linkage to the National Mortality Data Base. There is a strong positive association between radiation and breast cancer risk among the females in the cohort, but in contrast very little evidence of any increased risk in lung cancer. The results of this and other studies suggest that the effect of dose-rate and/or fractionation on cancer risk may will differ depending upon the particular cancer being considered. (author)

System simulation on fractionation radiation doses and radioisotope handling in Nuclear medicine

International Nuclear Information System (INIS)

Dytz, Aline Guerra; Dullius, Marcos Alexandre; Gomes, Camila e Silva

2008-01-01

This paper describes the practical and theoretical learning of students from Medical Physics course at the Fundacao Universidade Federal do Rio Grande (FURG) on fractionation radiation doses, radioisotope handling and elution of molybdenum generators (Mo-99) / technetium (Tc -99m)

In vivo dosimetry of high-dose fractionated irradiation in an experimental set-up with rats

Energy Technology Data Exchange (ETDEWEB)

Fortan, L; Van Hecke, H; Van Duyse, B; De Neve, W; De Meerleer, B [Ghent Rijksuniversiteit (Belgium). Kliniek voor Radiotherapie en Kerngeneeskunde; Pattyn, P; Van Renthergem, K [Ghent University (Belgium). Dept. of Surgery

1995-12-01

The feasibility to irradiate a limited section of a rat abdomen with well-defined edges was assessed. Because of the relative small volume involved, in vivo dosimetry with TLDs was necessary in providing us information about the accuracy of the irradiation method. Three to five days prior to the start of the radiotherapy treatment, two plastic strips - each containing a TLD-dosimeter (Harshaw TLD10 LiF rods, 1 mm dia x 6 mm) sealed in polyethylene tubing, and a lead bean - were implanted in the rat abdomen. The plastic strips made a closed loop around the bowel, through the mesenterium, and were fixed with a single stitch on the inner abdominal wall. One loop was made in the hepatic area; another was made in the lower abdomen, around the rectosigmoid. Conscious animals were irradiated using a purpose-build plexi-holder, with rear legs immobilised to avoid longitudinal movements. The implanted lead beans enabled us to simulate the rat prior to each radiation session. This way, the radiation field could be set up individually for each rat, in such way that the rectosigmoid area received full dose and the hepatic area received no irradiation dose at all. Irradiation was carried out, using 5 MV photons of a linear accelerator. Fifteen animals per group were irradiated according a conventional (2.0 Gy / fraction; 5 fractions / week) or a hyperfractionated (1.6 Gy / fraction; 2 daily fractions; 5 days / week) schedule, with different total doses. Prior to implantation, TLDs were individually calibrated and checked for stability. After removal from the abdomen . TLDs were tested again for accuracy. TLDs with an unacceptable read-out curve were rejected (about 2 to 4 TLDs per group of 15). The obtained accumulated doses - as determined by TLD read-outs-were comparable to the theoretical doses, indicating that fractionated radiation of small fields, with well defined mark off, in rats is feasible.

In vivo dosimetry of high-dose fractionated irradiation in an experimental set-up with rats

International Nuclear Information System (INIS)

Fortan, L.; Van Hecke, H.; Van Duyse, B.; De Neve, W.; De Meerleer, B.; Pattyn, P.; Van Renthergem, K.

1995-01-01

The feasibility to irradiate a limited section of a rat abdomen with well-defined edges was assessed. Because of the relative small volume involved, in vivo dosimetry with TLDs was necessary in providing us information about the accuracy of the irradiation method. Three to five days prior to the start of the radiotherapy treatment, two plastic strips - each containing a TLD-dosimeter (Harshaw TLD10 LiF rods, 1 mm dia x 6 mm) sealed in polyethylene tubing, and a lead bean - were implanted in the rat abdomen. The plastic strips made a closed loop around the bowel, through the mesenterium, and were fixed with a single stitch on the inner abdominal wall. One loop was made in the hepatic area; another was made in the lower abdomen, around the rectosigmoid. Conscious animals were irradiated using a purpose-build plexi-holder, with rear legs immobilised to avoid longitudinal movements. The implanted lead beans enabled us to simulate the rat prior to each radiation session. This way, the radiation field could be set up individually for each rat, in such way that the rectosigmoid area received full dose and the hepatic area received no irradiation dose at all. Irradiation was carried out, using 5 MV photons of a linear accelerator. Fifteen animals per group were irradiated according a conventional (2.0 Gy / fraction; 5 fractions / week) or a hyperfractionated (1.6 Gy / fraction; 2 daily fractions; 5 days / week) schedule, with different total doses. Prior to implantation, TLDs were individually calibrated and checked for stability. After removal from the abdomen . TLDs were tested again for accuracy. TLDs with an unacceptable read-out curve were rejected (about 2 to 4 TLDs per group of 15). The obtained accumulated doses - as determined by TLD read-outs-were comparable to the theoretical doses, indicating that fractionated radiation of small fields, with well defined mark off, in rats is feasible

Fractionated dose studies with X-rays and various alkylating agents in P388 mouse lymphoma cells

International Nuclear Information System (INIS)

Anderson, D.

1981-01-01

The fractionated dose technique has been used in P388F cells to examine the effects of X-rays and four alkylating agents on survival and induction of 5-iodo-2-deoxyuridine (IudR) resistant variants. Fractionation intervals up to 5 1/2 h were used for X-rays and for the alkylating agents up to 192 h. Fractionation of the X-ray dose resulted in a sparing effect for survival and variant induction. A sparing effect was also observed for survival after treatment with alkylating agents. However, variant frequencies were observed as large as or greater than those produced by the full doses of alkylating agents. For such agents this would suggest that survival and variant induction are independent events. Differences in the effects of X-rays and alkylating agents cannot be explained by differences in growth rate or the recovery of viability after treatment

Fractionated dose studies with X-rays and various alkylating agents in P388 mouse lymphoma cells

International Nuclear Information System (INIS)

Anderson, D.

1981-01-01

The fractionated dose technique was used in P388F cells to examine the effects of X-rays and four alkylating agents on survival and induction of 5-iodo-2-deoxyuridine (IudR) resistant variants. Fractionation intervals up to 51/2 h were used for X-rays and for the alkylating agents up to 192 h. Fractionation of the X-ray dose resulted in a sparing effect for survival and variant induction. A sparing effect was also observed for survival after treatment with alkylating agents. However, variant frequencies were observed as large as or greater than those produced by the full doses of alkylating agents. For such agents this would suggest that survival and variant induction are independent events. Differences in the effects of X-rays and alkylating agents cannot be explained by differences in growth rate or the recovery of viability after treatment. (author)

Dose fractionation effects in plateau-phase cultures of C3H 10T1/2 cells and their transformed counterparts

International Nuclear Information System (INIS)

Zeman, E.M.; Bedford, J.S.

1985-01-01

A comparison of γ-ray dose fractionation effects was made using plateau-phase cultures of C3H 10T1/2 cells and their transformed counterparts in an attempt to simulate basically similar populations of cells that differ primarily in their turnover rates. The status of cell populations with respect to their turnover rates may be an important factor influencing dose fractionation effects in early- and late-responding tissues. In this cell culture system, the rate of cell turnover was approximately three times higher for the plateau-phase transformed cultures. While the single acute dose survival curves for log-phase cells were indistinguishable, there were significant differences between the survival curves for plateau-phase cultures of the two cell types. Both cell lines had a similar capacity for repair of sublethal damage, but untransformed cells had a much greater capacity to repair potentially lethal damage in plateau phase. Multifraction survival curves were determined for both cell lines for doses per fraction ranging from 9.0 to 0.8 Gy, and from these isoeffect curves of log total dose versus dose per fraction were derived. The isoeffect curve for the slowly cycling, untransformed cells was found to be appreciably steeper than that for the more rapidly cycling transformed cells, a finding consistent with previously reported differences in dose fractionation isoeffect curves for early- and late-responding tissues in vivo

Dose fractionated gamma knife radiosurgery for large arteriovenous malformations on daily or alternate day schedule outside the linear quadratic model: Proof of concept and early results. A substitute to volume fractionation.

Science.gov (United States)

Mukherjee, Kanchan Kumar; Kumar, Narendra; Tripathi, Manjul; Oinam, Arun S; Ahuja, Chirag K; Dhandapani, Sivashanmugam; Kapoor, Rakesh; Ghoshal, Sushmita; Kaur, Rupinder; Bhatt, Sandeep

2017-01-01

To evaluate the feasibility, safety and efficacy of dose fractionated gamma knife radiosurgery (DFGKRS) on a daily schedule beyond the linear quadratic (LQ) model, for large volume arteriovenous malformations (AVMs). Between 2012-16, 14 patients of large AVMs (median volume 26.5 cc) unsuitable for surgery or embolization were treated in 2-3 of DFGKRS sessions. The Leksell G frame was kept in situ during the whole procedure. 86% (n = 12) patients had radiologic evidence of bleed, and 43% (n = 6) had presented with a history of seizures. 57% (n = 8) patients received a daily treatment for 3 days and 43% (n = 6) were on an alternate day (2 fractions) regimen. The marginal dose was split into 2 or 3 fractions of the ideal prescription dose of a single fraction of 23-25 Gy. The median follow up period was 35.6 months (8-57 months). In the three-fraction scheme, the marginal dose ranged from 8.9-11.5 Gy, while in the two-fraction scheme, the marginal dose ranged from 11.3-15 Gy at 50% per fraction. Headache (43%, n = 6) was the most common early postoperative complication, which was controlled with short course steroids. Follow up evaluation of at least three years was achieved in seven patients, who have shown complete nidus obliteration in 43% patients while the obliteration has been in the range of 50-99% in rest of the patients. Overall, there was a 67.8% reduction in the AVM volume at 3 years. Nidus obliteration at 3 years showed a significant rank order correlation with the cumulative prescription dose (p 0.95, P value 0.01), with attainment of near-total (more than 95%) obliteration rates beyond 29 Gy of the cumulative prescription dose. No patient receiving a cumulative prescription dose of less than 31 Gy had any severe adverse reaction. In co-variate adjusted ordinal regression, only the cumulative prescription dose had a significant correlation with common terminology criteria for adverse events (CTCAE) severity (P value 0.04), independent of age, AVM volume

Intradermal Administration of Fractional Doses of Inactivated Poliovirus Vaccine: A Dose-Sparing Option for Polio Immunization.

Science.gov (United States)

Okayasu, Hiromasa; Sein, Carolyn; Chang Blanc, Diana; Gonzalez, Alejandro Ramirez; Zehrung, Darin; Jarrahian, Courtney; Macklin, Grace; Sutter, Roland W

2017-07-01

A fractional dose of inactivated poliovirus vaccine (fIPV) administered by the intradermal route delivers one fifth of the full vaccine dose administered by the intramuscular route and offers a potential dose-sparing strategy to stretch the limited global IPV supply while further improving population immunity. Multiple studies have assessed immunogenicity of intradermal fIPV compared with the full intramuscular dose and demonstrated encouraging results. Novel intradermal devices, including intradermal adapters and disposable-syringe jet injectors, have also been developed and evaluated as alternatives to traditional Bacillus Calmette-Guérin needles and syringes for the administration of fIPV. Initial experience in India, Pakistan, and Sri Lanka suggests that it is operationally feasible to implement fIPV vaccination on a large scale. Given the available scientific data and operational feasibility shown in early-adopter countries, countries are encouraged to consider introducing a fIPV strategy into their routine immunization and supplementary immunization activities. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Limitations of a convolution method for modeling geometric uncertainties in radiation therapy: the radiobiological dose-per-fraction effect

International Nuclear Information System (INIS)

Song, William; Battista, Jerry; Van Dyk, Jake

2004-01-01

The convolution method can be used to model the effect of random geometric uncertainties into planned dose distributions used in radiation treatment planning. This is effectively done by linearly adding infinitesimally small doses, each with a particular geometric offset, over an assumed infinite number of fractions. However, this process inherently ignores the radiobiological dose-per-fraction effect since only the summed physical dose distribution is generated. The resultant potential error on predicted radiobiological outcome [quantified in this work with tumor control probability (TCP), equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and generalized equivalent uniform dose (gEUD)] has yet to be thoroughly quantified. In this work, the results of a Monte Carlo simulation of geometric displacements are compared to those of the convolution method for random geometric uncertainties of 0, 1, 2, 3, 4, and 5 mm (standard deviation). The α/β CTV ratios of 0.8, 1.5, 3, 5, and 10 Gy are used to represent the range of radiation responses for different tumors, whereas a single α/β OAR ratio of 3 Gy is used to represent all the organs at risk (OAR). The analysis is performed on a four-field prostate treatment plan of 18 MV x rays. The fraction numbers are varied from 1-50, with isoeffective adjustments of the corresponding dose-per-fractions to maintain a constant tumor control, using the linear-quadratic cell survival model. The average differences in TCP and EUD of the target, and in NTCP and gEUD of the OAR calculated from the convolution and Monte Carlo methods reduced asymptotically as the total fraction number increased, with the differences reaching negligible levels beyond the treatment fraction number of ≥20. The convolution method generally overestimates the radiobiological indices, as compared to the Monte Carlo method, for the target volume, and underestimates those for the OAR. These effects are interconnected and attributed

Effect of e-beam dose on the fractional density of Au-catalyzed GaAs nanowire growth

Energy Technology Data Exchange (ETDEWEB)

Park, Jeung Hun, E-mail: jeunghunpark@gmail.com [Department of Materials Science and Engineering, University of California Los Angeles, Los Angeles, CA 90095 (United States); Gambin, Vincent [Northrop Grumman Aerospace Systems, Redondo Beach, CA 90278 (United States); Kodambaka, Suneel, E-mail: kodambaka@ucla.edu [Department of Materials Science and Engineering, University of California Los Angeles, Los Angeles, CA 90095 (United States)

2016-05-31

Using Au/GaAs as a model system, the effect of initial catalyst patterning conditions on the growth of nanowire was studied. Resulting morphologies and fractional surface densities are determined as a function of e-beam dose, dot size, and inter-dot spacing using scanning and transmission electron microscopies. The majority of resulting nanowires grow randomly oriented with respect to the substrate. The nanowires are tapered with narrow tops, wider bases, and catalysts at the wire tips — characteristics of vapor–liquid–solid process. The base diameters of the wires are larger than the dot size, which is likely due to the non-catalyzed vapor–solid deposition along the sidewalls. The higher dose rate used in pattering leads to the formation of higher aspect ratio nanowires with narrower bases. The fractional surface density is found to increase linearly with the clearing dose and the critical dose for nanowire growth increases with decreasing catalyst pattern size and spacing. At a given dose, the fractional density increases with increasing Au dot size and with decreasing inter-dot spacing. Our results may provide new insights into the role of catalyst preparing conditions on the high density, wafer-scale growth of nanowires. - Highlights: • Initial Au catalyst layers are prepared using electron beam lithography. • GaAs nanowires are grown on GaAs(111)B using molecular beam epitaxy. • Effect of dose, size and spacing of Au dots on morphology and density is studied. • Density of nanowires is controlled by changing exposed dose on Au catalyst.

Universal Survival Curve and Single Fraction Equivalent Dose: Useful Tools in Understanding Potency of Ablative Radiotherapy

International Nuclear Information System (INIS)

Park, Clint; Papiez, Lech; Zhang Shichuan; Story, Michael; Timmerman, Robert D.

2008-01-01

Purpose: Overprediction of the potency and toxicity of high-dose ablative radiotherapy such as stereotactic body radiotherapy (SBRT) by the linear quadratic (LQ) model led to many clinicians' hesitating to adopt this efficacious and well-tolerated therapeutic option. The aim of this study was to offer an alternative method of analyzing the effect of SBRT by constructing a universal survival curve (USC) that provides superior approximation of the experimentally measured survival curves in the ablative, high-dose range without losing the strengths of the LQ model around the shoulder. Methods and Materials: The USC was constructed by hybridizing two classic radiobiologic models: the LQ model and the multitarget model. We have assumed that the LQ model gives a good description for conventionally fractionated radiotherapy (CFRT) for the dose to the shoulder. For ablative doses beyond the shoulder, the survival curve is better described as a straight line as predicted by the multitarget model. The USC smoothly interpolates from a parabola predicted by the LQ model to the terminal asymptote of the multitarget model in the high-dose region. From the USC, we derived two equivalence functions, the biologically effective dose and the single fraction equivalent dose for both CFRT and SBRT. Results: The validity of the USC was tested by using previously published parameters of the LQ and multitarget models for non-small-cell lung cancer cell lines. A comparison of the goodness-of-fit of the LQ and USC models was made to a high-dose survival curve of the H460 non-small-cell lung cancer cell line. Conclusion: The USC can be used to compare the dose fractionation schemes of both CFRT and SBRT. The USC provides an empirically and a clinically well-justified rationale for SBRT while preserving the strengths of the LQ model for CFRT

Influence of fractionation of dose on 3 year results of X-ray therapy of skin cancer

International Nuclear Information System (INIS)

Szymczyk, W.; Radziszewska, J.; Cyplik, I.; Glinska, H.

1985-01-01

Three-year results of X-ray therapy of skin cancer in 345 patients are presented. The dependence of results on the size of irradiated field and the method of dose fractionation is analysed. The clinical usefulness of a cumulative radiation effect (CRE) is evaluated. 96.5% of three-year cures were obtained. Recurrences amounted to 1.6% and necroses to 1.9% of treated lesions. It has been shown that treatment of small fields with 8-fractions gave equally positive results as with 15-fractions whereas in the treatment of large lesions the selection of CRE value, a number of fractions and dose should let the value of CRE minimally exceeds the level of tolerance of healthy tissues. The regard to CRE value in the treatment of large lesions or the introduction of additional dosimetric acts seems to be useful. 10 refs., 1 fig., 5 tabs. (author)

Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

International Nuclear Information System (INIS)

Lee, Eun-Jung; Kim, Jun Won; Yoo, Hyun; Kwak, Woori; Choi, Won Hoon; Cho, Seoae; Choi, Yu Jeong; Lee, Yoon-Jin; Cho, Jaeho

2015-01-01

We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm 2 fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL-33

Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

Energy Technology Data Exchange (ETDEWEB)

Lee, Eun-Jung, E-mail: forejs2@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kim, Jun Won, E-mail: JUNWON@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Yoo, Hyun, E-mail: gochunghee@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kwak, Woori, E-mail: asleo02@snu.ac.kr [Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-747 (Korea, Republic of); Choi, Won Hoon, E-mail: wonhoon@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Cho, Seoae, E-mail: seoae@cnkgenomics.com [C& K Genomics, Seoul National University Mt.4-2, Main Bldg. #514, SNU Research Park, NakSeoungDae, Gwanakgu, Seoul 151-919 (Korea, Republic of); Choi, Yu Jeong, E-mail: yunk9275@daum.net [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Lee, Yoon-Jin, E-mail: yjlee8@kirams.re.kr [Division of Radiation Effects, Research Center for Radiotherapy, Korea Institute of Radiological & Medical Sciences, Seoul 139-760 (Korea, Republic of); Cho, Jaeho, E-mail: jjhmd@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)

2015-08-14

We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm{sup 2} fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL

Fractional model for pharmacokinetics of high dose methotrexate in children with acute lymphoblastic leukaemia

Science.gov (United States)

Popović, Jovan K.; Spasić, Dragan T.; Tošić, Jela; Kolarović, Jovanka L.; Malti, Rachid; Mitić, Igor M.; Pilipović, Stevan; Atanacković, Teodor M.

2015-05-01

The aim of this study is to promote a model based on the fractional differential calculus related to the pharmacokinetic individualization of high dose methotrexate treatment in children with acute lymphoblastic leukaemia, especially in high risk patients. We applied two-compartment fractional model on 8 selected cases with the largest number (4-19) of measured concentrations, among 43 pediatric patients received 24-h methotrexate 2-5 g/m2 infusions. The plasma concentrations were determined by fluorescence polarization immunoassay. Our mathematical procedure, designed by combining Post's and Newton's method, was coded in Mathematica 8.0 and performed on Fujicu Celsius M470-2 PC. Experimental data show that most of the measured values of methotrexate were in decreasing order. However, in certain treatments local maximums were detected. On the other hand, integer order compartmental models do not give values which fit well with the observed data. By the use of our model, we obtained better results, since it gives more accurate behavior of the transmission, as well as the local maximums which were recognized in methotrexate monitoring. It follows from our method that an additional test with a small methotrexate dose can be suggested for the fractional system parameter identification and the prediction of a possible pattern with a full dose in the case of high risk patients. A special feature of the fractional model is that it can also recognize and better fit an observed non-monotonic behavior. A new parameter determination procedure can be successfully used.

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.

ANALYSIS OF RESPIRATORY DESPOSITION DOSE OF INHALED AMBIENT AEROSOLS FOR DIFFERENT SIZE FRACTIONS

Science.gov (United States)

ANALYSIS OF RESPIRATORY DEPOSITION DOSE OF INHALED AMBIENT AEROSOLS FOR DIFFERENT SIZE FRACTIONS. Chong S. Kim, SC. Hu**, PA Jaques*, US EPA, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711; **IIT Research Institute, Chicago, IL; *S...

Fractionated dose skews differentiation of Glial progenitor cells into immature oligodendrocytes and astrocytes, with lower mature oligodendrocytes formation, as compared to singe low dose of low and high LET radiation

International Nuclear Information System (INIS)

Sanchez, Zina; Pena, Louis; Naidu, Mamta

2010-01-01

In the proposed study, the effect of fractionated, low dose versus single low dose of low LET X-rays and charged particles on induction of base excision repair enzyme Apurinic Endonuclease-1 (Ape1) are determined, which is known to inhibit cell differentiation, and found that at lower doses of 10,25 and 50 cGy there was a very significant induction of Apel which correlated to number of fractions, whereas at 100 cGy this induction was significantly lower. Also, there was a clear correlation between increase in fractions and higher immature OL and astrocyte formation

The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd→Be) for normal tissues. Pt. 3

International Nuclear Information System (INIS)

Rezvani, M.; Hopewell, J.W.; Robbins, M.E.C.; Hamlet, R.; Barnes, D.W.H.; Sansom, J.M.; Adams, P.J.V.

1990-01-01

The effect of single and fractionated doses of fast neutrons (42 MeV d→Bc ) on the early and late radiation responses of the pig lung have been assessed by the measurement of changes in lung function using a 133 Xe washout technique. The results obtained for irradiation schedules with fast neutrons have been compared with those after photon irradiation. There was no statistically significant difference between the values for the relative biological effectiveness (RBE) for the early and late radiation response of the lung. The RBE of the neutron beam increased with decreasing size of dose/fraction with an upper limit value of 4.39 ± 0.94 for infinitely small X-ray doses per fraction. (author)

Mutation induction in haploid yeast after split-dose radiation-exposure. I. Fractionated UV-irradiation.

Science.gov (United States)

Schenk, K; Zölzer, F; Kiefer, J

1989-01-01

Mutation induction was investigated in wild-type haploid yeast Saccharomyces cerevisiae after split-dose UV-irradiation. Cells were exposed to fractionated 254 nm-UV-doses separated by intervals from 0 to 6 h with incubation either on non-nutrient or nutrient agar between. The test parameter was resistance to canavanine. If modifications of sensitivity due to incubation are appropriately taken into account there is no change of mutation frequency.

High-Dose-Rate Brachytherapy Boost for Prostate Cancer: Comparison of Two Different Fractionation Schemes

International Nuclear Information System (INIS)

Kaprealian, Tania; Weinberg, Vivian; Speight, Joycelyn L.; Gottschalk, Alexander R.; Roach, Mack; Shinohara, Katsuto; Hsu, I.-Chow

2012-01-01

Purpose: This is a retrospective study comparing our experience with high-dose-rate (HDR) brachytherapy boost for prostate cancer, using two different fractionation schemes, 600 cGy × 3 fractions (patient group 1) and 950 cGy × 2 fractions (patient group 2). Methods and Materials: A total of 165 patients were treated for prostate cancer using external beam radiation therapy up to a dose of 45 Gy, followed by an HDR brachytherapy prostate radiation boost. Between July 1997 and Nov 1999, 64 patients were treated with an HDR boost of 600 cGy × 3 fractions; and between June 2000 and Nov 2005, 101 patients were treated with an HDR boost of 950 cGy × 2 fractions. All but 9 patients had at least one of the following risk features: pretreatment prostate-specific antigen (PSA) level >10, a Gleason score ≥7, and/or clinical stage T3 disease. Results: Median follow-up was 105 months for group 1 and 43 months for group 2. Patients in group 2 had a greater number of high-risk features than group 1 (p = 0.02). Adjusted for comparable follow-up, there was no difference in biochemical no-evidence-of-disease (bNED) rate between the two fractionation scheme approaches, with 5-year Kaplan-Meier estimates of 93.5% in group 1 and 87.3% in group 2 (p = 0.19). The 5-year estimates of progression-free survival were 86% for group 1 and 83% for group 2 (p = 0.53). Among high-risk patients, there were no differences in bNED or PFS rate due to fractionation. Conclusions: Results were excellent for both groups. Adjusted for comparable follow-up, no differences were found between groups.

Estimation of the effectivity of gamma teletherapy with fractionated daily doses in inoperable malignant tumors

International Nuclear Information System (INIS)

Mardynskij, Yu.S.; Leskov, V.P.

1982-01-01

131 patients with lung, esophagus, rectum and mandibulofacial tumors, most of them being inoperable, were treated with fractionated gamma teletherapy. The daily focus dose of 2-2.2 Gy was applied in 2 fractions with an interval of 4-6 h. The total focus dose of one course of treatment was 40-70 Gy. In 56 patients (42.7%) a complete regression of the tumors and of the increased regional lymph nodes was obtained. The irradiation by the mentioned technique showed the highest effectivity for tumors of the lung and the esophagus. The diminished frequency and an easier progress of the radiation reactions are important because they often prevent to carry out a radical therapy. (author)

Analyzed immunogenicity of fractional doses of Sabin-inactivated poliovirus vaccine (sIPV) with intradermal delivery in rats.

Science.gov (United States)

Ma, Lei; Cai, Wei; Sun, Mingbo; Cun, Yina; Zhou, Jian; Liu, Jing; Hu, Wenzhu; Zhang, Xinwen; Song, Shaohui; Jiang, Shude; Liao, Guoyang

2016-12-01

The live-attenuated oral polio vaccine (OPV) will be no longer used when wild poliovirus (WPV) eliminating in worldwide, according to GPEI (the Global Polio Eradication Initiative) Reports. It is planning to replace OPV by Sabin-based inactivated poliovirus vaccine (sIPV) in developing countries, with purpose of reducing of the economic burden and maintaining of the appropriate antibody levels in population. It studied serial fractional doses immunized by intradermal injection (ID) in rats, to reduce consume of antigen and financial burden, maintaining sufficient immunogenicity; Methods: Study groups were divided in 4 groups of dose gradient, which were one-tenth (1/10), one-fifth (1/5), one-third (1/3) and one-full dose (1/1), according to the volume of distribution taken from the same batch of vaccine (sIPV). Wistar rats were injected intradermally with the needle and syringe sing the mantoux technique taken once month for 3 times. It was used as positive control that intramuscular inoculation (IM) was injected with one-full dose (1/1) with same batch of sIPV. PBS was used as negative control. Blood samples were collected via tail vein. After 30 d with 3 round of immunization, it analyzed the changes of neutralization antibody titers in the each group by each immunization program end; Results: The results of seroconversion had positive correlation with different doses in ID groups. The higher concentration of D-antigen (D-Ag) could conduct higher seroconversion. Furthermore, different types of viruses had different seroconversion trend. It showed that the geometric mean titers (GMTs) of each fractional-dose ID groups increased by higher concentration of D-Ag, and it got significant lower than the full-dose IM group. At 90 th days of immunization, the GMTs for each poliovirus subtypes of fractional doses were almost higher than 1:8, implied that it could be meaning positive seroprotection titer for polio vaccine types, according to WHO suggestion; Conclusions

Low-dose X-irradiation of adjuvant-induced arthritis in rats. Efficacy of different fractionation schedules

International Nuclear Information System (INIS)

Liebmann, A.; Hindemith, M.; Jahns, J.; Kamprad, F.; Hildebrandt, G.; Madaj-Sterba, P.; Weisheit, S.

2004-01-01

Background and purpose: low-dose radiotherapy is widely accepted as a very effective treatment option for inflammatory symptoms associated with painful degenerative joint disorders. Radiation doses and fractionation schedules in practical use are empirical and mainly based on clinical observations. Experimental data are rare. The efficacy of low-dose X-irradiation on adjuvant induced arthritis in rats using different fractionation schemes was investigated in vivo, in order to explore whether there is a dose and fractionation dependence. Material and methods: adjuvant arthritis in female lewis rats (n = 128) was induced by intradermal injection of heat-inactivated Mycobacterium tuberculosis on day 0. Both arthritic hind paws were sham-irradiated (group 1: days 10-14; group 2: days 15-19; group 3: days 22-26) or X-irradiated with either 5 x 1.0 Gy (group 4: days 10-14; group 6: days 15-19; group 8: days 22-26; group 10: days 10, 12, 14, 16, and 18) or 5 x 0.5 Gy (group 5: days 10-14; group 7: days 15-19; group 9: days 22-26; group 11: days 10, 12, 14, 16, and 18; group 12: days 10-14 and 22-26). The clinical parameters arthritis score (AS), hind paw volume (HPV), and body weight were determined. Results: a significant decrease of the clinical arthritis parameters was observed following 5 x 0.5 Gy or 5 x 1.0 Gy during the acute maximum of the inflammatory response (days 15-19). The most pronounced treatment effect was reached after two daily fractionated series of 5 x 0.5 Gy with an early treatment onset (days 10-14) and repetition in interval (days 22-26). After the application of 5 x 1.0 Gy on days 10-14 or in a protracted scheme (days 10, 12, 14, 16, and 18), only a nonsignificant positive trend could be detected. Daily fractionated X-irradiation in the chronic phase of adjuvant arthritis (days 22-26) did not show any positive clinical effect. Conclusion: low-dose radiotherapy is able to prevent a full-blown arthritic reaction if given during the florid phase of

Fractionated total body irradiation and autologous bone marrow transplantation in dogs: Hemopoietic recovery after various marrow cell doses

International Nuclear Information System (INIS)

Bodenburger, U.; Kolb, H.J.; Thierfelder, S.; Netzel, B.; Schaeffer, E.; Kolb, H.

1980-01-01

Hemopoietic recovery was studied in dogs given 2400 R fractionated total body irradiation within one week and graded doses of cryopreserved autologous bone marrow. Complete hemopoietic recovery including histology was observed after this dose and sufficient doses of marrow cells. Doses of more than 5.5 x 10 7 mononuclear marrow cells/kg body weight were sufficient for complete recovery in all dogs, 1.5 to 5.5 x 10 7 cells/kg were effective in some of the dogs and less than 1.5 x 10 7 cells/kg were insufficient for complete recovery. Similarly, more than 30000 CFUsub(c)/kg body weight were required for hemopoietic recovery. The optimal marrow cell dose which has been defined as the minimal dose required for the earliest possible recovery of leukocyte and platelet counts was 7-8 x 10 7 mononuclear marrow cells/kg body weight. It has been concluded that fractionated total body irradiation with 2400 R dose not require greater doses of marrow cells for hemopoietic reconstitution than lower single doses and that the hemopoietic microenvironment is not persistently disturbed after this dose. (author)

Dose Evaluation of Fractionated Schema and Distance From Tumor to Spinal Cord for Spinal SBRT with Simultaneous Integrated Boost: A Preliminary Study.

Science.gov (United States)

Yang, Hao; Cai, Bo-ning; Wang, Xiao-shen; Cong, Xiao-hu; Xu, Wei; Wang, Jin-yuan; Yang, Jun; Xu, Shou-ping; Ju, Zhong-jian; Ma, Lin

2016-02-23

BACKGROUND This study investigated and quantified the dosimetric impact of the distance from the tumor to the spinal cord and fractionation schemes for patients who received stereotactic body radiation therapy (SBRT) and hypofractionated simultaneous integrated boost (HF-SIB). MATERIAL AND METHODS Six modified planning target volumes (PTVs) for 5 patients with spinal metastases were created by artificial uniform extension in the region of PTV adjacent spinal cord with a specified minimum tumor to cord distance (0-5 mm). The prescription dose (biologic equivalent dose, BED) was 70 Gy in different fractionation schemes (1, 3, 5, and 10 fractions). For PTV V100, Dmin, D98, D95, and D1, spinal cord dose, conformity index (CI), V30 were measured and compared. RESULTS PTV-to-cord distance influenced PTV V100, Dmin, D98, and D95, and fractionation schemes influenced Dmin and D98, with a significant difference. Distances of ≥2 mm, ≥1 mm, ≥1 mm, and ≥0 mm from PTV to spinal cord meet dose requirements in 1, 3, 5, and 10 fractionations, respectively. Spinal cord dose, CI, and V30 were not impacted by PTV-to-cord distance and fractionation schemes. CONCLUSIONS Target volume coverage, Dmin, D98, and D95 were directly correlated with distance from the spinal cord for spine SBRT and HF-SIB. Based on our study, ≥2 mm, ≥1 mm, ≥1 mm, and ≥0 mm distance from PTV to spinal cord meets dose requirements in 1, 3, 5 and 10 fractionations, respectively.

High Dose Rate Brachytherapy in Two 9 Gy Fractions in the Treatment of Locally Advanced Cervical Cancer - a South Indian Institutional Experience.

Science.gov (United States)

Ghosh, Saptarshi; Rao, Pamidimukkala Bramhananda; Kotne, Sivasankar

2015-01-01

Although 3D image based brachytherapy is currently the standard of treatment in cervical cancer, most of the centres in developing countries still practice orthogonal intracavitary brachytherapy due to financial constraints. The quest for optimum dose and fractionation schedule in high dose rate (HDR) intracavitary brachytherapy (ICBT) is still ongoing. While the American Brachytherapy Society recommends four to eight fractions of each less than 7.5 Gy, there are some studies demonstrating similar efficacy and comparable toxicity with higher doses per fraction. To assess the treatment efficacy and late complications of HDR ICBT with 9 Gy per fraction in two fractions. This is a prospective institutional study in Southern India carried on from 1st June 2012 to 31st July 2014. In this period, 76 patients of cervical cancer satisfying our inclusion criteria were treated with concurrent chemo-radiation following ICBT with 9 Gy per fraction in two fractions, five to seven days apart. The median follow-up period in the study was 24 months (range 10.6 - 31.2 months). The 2 year actuarial local control rate, disease-free survival and overall survival were 88.1%, 84.2% and 81.8% respectively. Although 38.2% patients suffered from late toxicity, only 3 patients had grade III late toxicity. In our experience, HDR brachytherapy with 9 Gy per fraction in two fractions is an effective dose fractionation for the treatment of cervical cancer with acceptable toxicity.

nduced hyperlipidemic rats. Methods: Column chromatographic fractionation of butanol fraction of total methanol extract of leaves of Bauhinia variegata (Linn. yields four sub-fractions (sub-fraction A-D. All sub-fractions tested for their anti-hyperlipidemic activity. Sub-fractions administered at a dose of 65 mg/kg (oral to the Triton WR-1339 induced hyperlipidemic rats and total cholesterol, triglycerides, HDL, LDL and VLDL

Directory of Open Access Journals (Sweden)

Deepak Kumar

2012-10-01

Full Text Available Objective: To investigate the effect and evaluation of Anti-hyperlipidemic activity guided subfraction isolated from total methanolic extract of Bauhinia variegata (Linn. leaves on Triton WR-1339 induced hyperlipidemic rats. Methods: Column chromatographic fractionation of butanol fraction of total methanol extract of leaves of Bauhinia variegata (Linn. yields four subfractions (sub-fraction A-D. All sub-fractions tested for their anti-hyperlipidemic activity. Subfractions administered at a dose of 65 mg/kg (oral to the Triton WR-1339 induced hyperlipidemic rats and total cholesterol, triglycerides, HDL, LDL and VLDL level in the blood were checked. Results: Sub-fraction D showed significant reduction (P<0.05 among four sub-fraction in comparison with standard drug fenofibrate. Conclusions: From the above study it could be concluded that butanol sub-fraction D of Bauhinia variegata (Linn. not only have resulted in significant reduction in cholesterol, triglyceride, LDL, VLDL level but also increases the HDL level at a reduced dose level.

The HYP-RT Hypoxic Tumour Radiotherapy Algorithm and Accelerated Repopulation Dose per Fraction Study

Directory of Open Access Journals (Sweden)

W. M. Harriss-Phillips

2012-01-01

Full Text Available The HYP-RT model simulates hypoxic tumour growth for head and neck cancer as well as radiotherapy and the effects of accelerated repopulation and reoxygenation. This report outlines algorithm design, parameterisation and the impact of accelerated repopulation on the increase in dose/fraction needed to control the extra cell propagation during accelerated repopulation. Cell kill probabilities are based on Linear Quadratic theory, with oxygenation levels and proliferative capacity influencing cell death. Hypoxia is modelled through oxygen level allocation based on pO2 histograms. Accelerated repopulation is modelled by increasing the stem cell symmetrical division probability, while the process of reoxygenation utilises randomised pO2 increments to the cell population after each treatment fraction. Propagation of 108 tumour cells requires 5–30 minutes. Controlling the extra cell growth induced by accelerated repopulation requires a dose/fraction increase of 0.5–1.0 Gy, in agreement with published reports. The average reoxygenation pO2 increment of 3 mmHg per fraction results in full tumour reoxygenation after shrinkage to approximately 1 mm. HYP-RT is a computationally efficient model simulating tumour growth and radiotherapy, incorporating accelerated repopulation and reoxygenation. It may be used to explore cell kill outcomes during radiotherapy while varying key radiobiological and tumour specific parameters, such as the degree of hypoxia.

A simple method to calculate the influence of dose inhomogeneity and fractionation in normal tissue complication probability evaluation

International Nuclear Information System (INIS)

Begnozzi, L.; Gentile, F.P.; Di Nallo, A.M.; Chiatti, L.; Zicari, C.; Consorti, R.; Benassi, M.

1994-01-01

Since volumetric dose distributions are available with 3-dimensional radiotherapy treatment planning they can be used in statistical evaluation of response to radiation. This report presents a method to calculate the influence of dose inhomogeneity and fractionation in normal tissue complication probability evaluation. The mathematical expression for the calculation of normal tissue complication probability has been derived combining the Lyman model with the histogram reduction method of Kutcher et al. and using the normalized total dose (NTD) instead of the total dose. The fitting of published tolerance data, in case of homogeneous or partial brain irradiation, has been considered. For the same total or partial volume homogeneous irradiation of the brain, curves of normal tissue complication probability have been calculated with fraction size of 1.5 Gy and of 3 Gy instead of 2 Gy, to show the influence of fraction size. The influence of dose distribution inhomogeneity and α/β value has also been simulated: Considering α/β=1.6 Gy or α/β=4.1 Gy for kidney clinical nephritis, the calculated curves of normal tissue complication probability are shown. Combining NTD calculations and histogram reduction techniques, normal tissue complication probability can be estimated taking into account the most relevant contributing factors, including the volume effect. (orig.) [de

Functional and morphological changes in pig skin after single or fractionated doses in x rays

International Nuclear Information System (INIS)

Young, C.M.A.; Hopewell, J.W.

1982-01-01

The flank skin of pigs has been treated with either single or fractionated doses of x-irradiation. A single dose (2070 cGy) was compared with treatment given as 6 fractions in 18 days (6f/18 days; 3780 cGy) or 30 fractions in 39 days (30f/39 days; 8000 cGy). The doses were selected on the basis that similar levels of late tissue damage would result. Radiation induced changes in the skin were assessed by observing the skin reactions and by the measurement of isotope clearance (functional study), relative field contraction, dermal and epidermal thickness and dermal vascular density (morphological studies). In the three treatment groups the early radiation reaction varied considerably. In the first wave reaction (3 to 6 weeks after treatment) bright red erythema was recorded in many fields but moist desquamation developed only in the 30f/39 days treatment group. The second wave (10-16 weeks) was characterized by an ischemic mauve/dusky reaction. Dermal necrosis developed in 50% of the single dose fields. In the 30f/39 days regimen persistent moist desquamation progressed to dermal necrosis. Neither desquamation nor necrosis developed after 6f/18 days. Different levels of vascular damage in the dermis were assessed using an isotope clearance technique; for example in the early reaction significant changes were recorded in the papillary dermis (faster clearance) prior to the development of moist desquamation (30f/39 days) and in the reticular dermis (slower clearance) before necrosis (single dose). Changes in clearance rates have been correlated with changes in the vascular density and thickness of the dermis. Between 26 and 52 weeks (the late reaction) relative field contraction was slightly greater in the 30f/39 days group than in the other treatment groups

Dose fractionation theorem in 3-D reconstruction (tomography)

Energy Technology Data Exchange (ETDEWEB)

Glaeser, R.M. [Lawrence Berkeley National Lab., CA (United States)

1997-02-01

It is commonly assumed that the large number of projections for single-axis tomography precludes its application to most beam-labile specimens. However, Hegerl and Hoppe have pointed out that the total dose required to achieve statistical significance for each voxel of a computed 3-D reconstruction is the same as that required to obtain a single 2-D image of that isolated voxel, at the same level of statistical significance. Thus a statistically significant 3-D image can be computed from statistically insignificant projections, as along as the total dosage that is distributed among these projections is high enough that it would have resulted in a statistically significant projection, if applied to only one image. We have tested this critical theorem by simulating the tomographic reconstruction of a realistic 3-D model created from an electron micrograph. The simulations verify the basic conclusions of high absorption, signal-dependent noise, varying specimen contrast and missing angular range. Furthermore, the simulations demonstrate that individual projections in the series of fractionated-dose images can be aligned by cross-correlation because they contain significant information derived from the summation of features from different depths in the structure. This latter information is generally not useful for structural interpretation prior to 3-D reconstruction, owing to the complexity of most specimens investigated by single-axis tomography. These results, in combination with dose estimates for imaging single voxels and measurements of radiation damage in the electron microscope, demonstrate that it is feasible to use single-axis tomography with soft X-ray microscopy of frozen-hydrated specimens.

Dose fractionation theorem in 3-D reconstruction (tomography)

International Nuclear Information System (INIS)

Glaeser, R.M.

1997-01-01

It is commonly assumed that the large number of projections for single-axis tomography precludes its application to most beam-labile specimens. However, Hegerl and Hoppe have pointed out that the total dose required to achieve statistical significance for each voxel of a computed 3-D reconstruction is the same as that required to obtain a single 2-D image of that isolated voxel, at the same level of statistical significance. Thus a statistically significant 3-D image can be computed from statistically insignificant projections, as along as the total dosage that is distributed among these projections is high enough that it would have resulted in a statistically significant projection, if applied to only one image. We have tested this critical theorem by simulating the tomographic reconstruction of a realistic 3-D model created from an electron micrograph. The simulations verify the basic conclusions of high absorption, signal-dependent noise, varying specimen contrast and missing angular range. Furthermore, the simulations demonstrate that individual projections in the series of fractionated-dose images can be aligned by cross-correlation because they contain significant information derived from the summation of features from different depths in the structure. This latter information is generally not useful for structural interpretation prior to 3-D reconstruction, owing to the complexity of most specimens investigated by single-axis tomography. These results, in combination with dose estimates for imaging single voxels and measurements of radiation damage in the electron microscope, demonstrate that it is feasible to use single-axis tomography with soft X-ray microscopy of frozen-hydrated specimens

Effect of intra-fraction motion on the accumulated dose for free-breathing MR-guided stereotactic body radiation therapy of renal-cell carcinoma

Science.gov (United States)

Stemkens, Bjorn; Glitzner, Markus; Kontaxis, Charis; de Senneville, Baudouin Denis; Prins, Fieke M.; Crijns, Sjoerd P. M.; Kerkmeijer, Linda G. W.; Lagendijk, Jan J. W.; van den Berg, Cornelis A. T.; Tijssen, Rob H. N.

2017-09-01

Stereotactic body radiation therapy (SBRT) has shown great promise in increasing local control rates for renal-cell carcinoma (RCC). Characterized by steep dose gradients and high fraction doses, these hypo-fractionated treatments are, however, prone to dosimetric errors as a result of variations in intra-fraction respiratory-induced motion, such as drifts and amplitude alterations. This may lead to significant variations in the deposited dose. This study aims to develop a method for calculating the accumulated dose for MRI-guided SBRT of RCC in the presence of intra-fraction respiratory variations and determine the effect of such variations on the deposited dose. For this, RCC SBRT treatments were simulated while the underlying anatomy was moving, based on motion information from three motion models with increasing complexity: (1) STATIC, in which static anatomy was assumed, (2) AVG-RESP, in which 4D-MRI phase-volumes were time-weighted, and (3) PCA, a method that generates 3D volumes with sufficient spatio-temporal resolution to capture respiration and intra-fraction variations. Five RCC patients and two volunteers were included and treatments delivery was simulated, using motion derived from subject-specific MR imaging. Motion was most accurately estimated using the PCA method with root-mean-squared errors of 2.7, 2.4, 1.0 mm for STATIC, AVG-RESP and PCA, respectively. The heterogeneous patient group demonstrated relatively large dosimetric differences between the STATIC and AVG-RESP, and the PCA reconstructed dose maps, with hotspots up to 40% of the D99 and an underdosed GTV in three out of the five patients. This shows the potential importance of including intra-fraction motion variations in dose calculations.

Effect of dose fractionation of 60Co gamma radiation on longevity and reproduction of Sitophilus granarius (L., 1785) (Col., Curculionidae) in wheat

International Nuclear Information System (INIS)

Arthur, V.; Walder, J.M.M.; Wiendl, F.M.; Domarco, R.E.; Haddad, S.S.

1987-01-01

The effects of fractionated doses of gamma radiation in different interval of time on longevity and reproductivity of Sitophilus granarius (L., 1785) are studied. Gamma radiation was provided at dose rate of 1.56 kGy/hour by a Cobalt 60 source (Gammabeam-650). The insects were divided in two sets: one was irradiated at acute doses and the other in fractionated doses, with interval of 48 hours. Both sets received doses of 0,40, 50, 60, 70, 80, 90 and 100Gy. Mortality and and emergency were determined weekly. (M.A.C.) [pt

Single-fraction stereotactic radiotherapy: a dose-response analysis of arteriovenous malformation obliteration

International Nuclear Information System (INIS)

Touboul, Emmanuel; Al Halabi, Assem; Buffat, Laurent; Merienne, Louis; Huart, Judith; Schlienger, Michel; Lefkopoulos, Dimitrios; Mammar, Hamid; Missir, Odile; Meder, Jean-Francois; Laurent, Alex; Housset, Martin

1998-01-01

Purpose: Stereotactic radiotherapy delivered in a high-dose single fraction is an effective technique to obliterate intracranial arteriovenous malformations (AVM). To attempt to analyze the relationships between dose, volume, and obliteration rates, we studied a group of patients treated using single-isocenter treatment plans. Methods and Materials: From May 1986 to December 1989, 100 consecutive patients with angiographically proven AVM had stereotactic radiotherapy delivered as a high-dose single fraction using a single-isocenter technique. Distribution according to Spetzler-Martin grade was as follows: 79 grade 1-3, three grade 4, 0 grade 5, and 18 grade 6. The target volume was spheroid in 74 cases, ellipsoid in 11, and large and irregular in 15. The targeted volume of the nidus was estimated using two-dimensional stereotactic angiographic data and, calculated as an ovoid-shaped lesion, was 1900 ± 230 mm 3 (median 968 mm 3 ; range 62-11, 250 mm 3 ). The mean minimum target dose (D min ) was 19 ± 0.6 Gy (median 20 Gy; range: 3-31.5). The mean volume within the isodose which corresponded to the minimum target dose was 2500 ± 300 mm 3 (median 1200 mm 3 ; range 75-14 900 mm 3 ). The mean maximum dose (D max ) was 34.5 ± 0.5 Gy (median 35 Gy; range 15-45). The mean angiographic follow-up was 42 ± 2.3 months (median 37.5; range 7-117). Results: The absolute obliteration rate was 51%. The 5-year actuarial obliteration rate was 62.5 ± 7%. After univariate analysis, AVM obliteration was influenced by previous surgery (p = 0.0007), D min by steps of 5 Gy (p = 0.005), targeted volume of the nidus (≤968 mm 3 vs. >968 mm 3 ; p = 0.015), and grade according to Spetzler-Martin (grade 1-3 vs. grade 4-6; p = 0.011). After multivariate analysis, the independent factors influencing AVM obliteration were the D min [relative risk (RR) 1.9; 95% confidence interval (CI) 1.4-2.5; p min but does not seem to be influenced by D max and the targeted volume of the nidus

Artificial neural network based gynaecological image-guided adaptive brachytherapy treatment planning correction of intra-fractional organs at risk dose variation.

Science.gov (United States)

Jaberi, Ramin; Siavashpour, Zahra; Aghamiri, Mahmoud Reza; Kirisits, Christian; Ghaderi, Reza

2017-12-01

Intra-fractional organs at risk (OARs) deformations can lead to dose variation during image-guided adaptive brachytherapy (IGABT). The aim of this study was to modify the final accepted brachytherapy treatment plan to dosimetrically compensate for these intra-fractional organs-applicators position variations and, at the same time, fulfilling the dosimetric criteria. Thirty patients with locally advanced cervical cancer, after external beam radiotherapy (EBRT) of 45-50 Gy over five to six weeks with concomitant weekly chemotherapy, and qualified for intracavitary high-dose-rate (HDR) brachytherapy with tandem-ovoid applicators were selected for this study. Second computed tomography scan was done for each patient after finishing brachytherapy treatment with applicators in situ. Artificial neural networks (ANNs) based models were used to predict intra-fractional OARs dose-volume histogram parameters variations and propose a new final plan. A model was developed to estimate the intra-fractional organs dose variations during gynaecological intracavitary brachytherapy. Also, ANNs were used to modify the final brachytherapy treatment plan to compensate dosimetrically for changes in 'organs-applicators', while maintaining target dose at the original level. There are semi-automatic and fast responding models that can be used in the routine clinical workflow to reduce individually IGABT uncertainties. These models can be more validated by more patients' plans to be able to serve as a clinical tool.

Artificial neural network based gynaecological image-guided adaptive brachytherapy treatment planning correction of intra-fractional organs at risk dose variation

Directory of Open Access Journals (Sweden)

Ramin Jaberi

2017-12-01

Full Text Available Purpose : Intra-fractional organs at risk (OARs deformations can lead to dose variation during image-guided adaptive brachytherapy (IGABT. The aim of this study was to modify the final accepted brachytherapy treatment plan to dosimetrically compensate for these intra-fractional organs-applicators position variations and, at the same time, fulfilling the dosimetric criteria. Material and methods : Thirty patients with locally advanced cervical cancer, after external beam radiotherapy (EBRT of 45-50 Gy over five to six weeks with concomitant weekly chemotherapy, and qualified for intracavitary high-dose-rate (HDR brachytherapy with tandem-ovoid applicators were selected for this study. Second computed tomography scan was done for each patient after finishing brachytherapy treatment with applicators in situ. Artificial neural networks (ANNs based models were used to predict intra-fractional OARs dose-volume histogram parameters variations and propose a new final plan. Results : A model was developed to estimate the intra-fractional organs dose variations during gynaecological intracavitary brachytherapy. Also, ANNs were used to modify the final brachytherapy treatment plan to compensate dosimetrically for changes in ‘organs-applicators’, while maintaining target dose at the original level. Conclusions : There are semi-automatic and fast responding models that can be used in the routine clinical workflow to reduce individually IGABT uncertainties. These models can be more validated by more patients’ plans to be able to serve as a clinical tool.

Interstitial high-dose-rate brachytherapy boost: The feasibility and cosmetic outcome of a fractionated outpatient delivery scheme

International Nuclear Information System (INIS)

Manning, Matthew A.; Arthur, Douglas W.; Schmidt-Ullrich, Rupert K.; Arnfield, Mark R.; Amir, Cyrus; Zwicker, Robert D.

2000-01-01

Purpose: To evaluate the feasibility, potential toxicity, and cosmetic outcome of fractionated interstitial high dose rate (HDR) brachytherapy boost for the management of patients with breast cancer at increased risk for local recurrence. Methods and Materials: From 1994 to 1996, 18 women with early stage breast cancer underwent conventionally fractionated whole breast radiotherapy (50-50.4 Gy) followed by interstitial HDR brachytherapy boost. All were considered to be at high risk for local failure. Seventeen had pathologically confirmed final surgical margins of less than 2 mm or focally positive. Brachytherapy catheter placement and treatment delivery were conducted on an outpatient basis. Preplanning was used to determine optimal catheter positions to enhance dose homogeneity of dose delivery. The total HDR boost dose was 15 Gy delivered in 6 fractions of 2.5 Gy over 3 days. Local control, survival, late toxicities (LENT-SOMA), and cosmetic outcome were recorded in follow-up. In addition, factors potentially influencing cosmesis were analyzed by logistic regression analysis. Results: The minimum follow-up is 40 months with a median 50 months. Sixteen patients were alive without disease at last follow-up. There have been no in-breast failures observed. One patient died with brain metastases, and another died of unrelated causes without evidence of disease. Grade 1-2 late toxicities included 39% with hyperpigmentation, 56% with detectable fibrosis, 28% with occasional discomfort, and 11% with visible telangiectasias. Grade 3 toxicity was reported in one patient as persistent discomfort. Sixty-seven percent of patients were considered to have experienced good/excellent cosmetic outcomes. Factors with a direct relationship to adverse cosmetic outcome were extent of surgical defect (p = 0.00001), primary excision volume (p = 0.017), and total excision volume (p = 0.015). Conclusions: For high risk patients who may benefit from increased doses, interstitial HDR

Dose-rate effects in synchronous mammalian cells in culture. II. A comparison of the life cycle of HeLa cells during continuous irradiation or multiple-dose fractionation

International Nuclear Information System (INIS)

Mitchell, J.B.; Bedford, J.S.

1977-01-01

The life cycle of synchronized S3 HeLa cells was examined during continuous irradiation at a dose rate of approximately 37 rad/hr and during multiple dose fractionation schedules of the same average dose rate (total dose / overall time = average dose rate). For all regimes given at this dose rate the effects on the life cyclee were similar. Cells progressed through G1 and S without appreciable delay and experienced a minimum G2 delay of about 10 hr. Cells eventually entered mitosis but virtually none were able to complete a successful division

Effects of low-dose continuously fractionated X-ray irradiation on murine peripheral blood lymphocytes

International Nuclear Information System (INIS)

Xie Yi; Zhang Hong; Dang Bingrong; Hao Jifang; Guo Hongyun; Wang Xiaohu

2007-01-01

For estimating biological risks from low doses continual irradiation, we investigated the effects of exposure to continuously fractionated X-rays on murine immune system. The BALB/c mice were irradiated with 0.07Gy at the first day and 0.08 Gy/d in the following 12 days at a dose rate of 0.2 Gy/min. The peripheral blood lymphocyte cycle and death were determined by flow cytometry at the cumulative doses of 0, 0.07, 0.23, 0.39, 0.55, 0.71, 0.87 and 1.03 Gy respectively. The results showed that the cycle of peripheral blood lymphocyte was arrested in G 0 /G 1 at cumulative doses of 0.07, 0.23, 0.71 and 0.87 Gy, and in G 2 /M at cumulative doses of 0.39 and 1.03 Gy; the percentage of death of peripheral blood lymphocyte was ascended with dose increasing, and reached the death peak at cumulative doses of 0.71 Gy. The results suggested that low doses continual X-rays total-body irradiated could result in changes of cellular cycle and death, and some damages to immunocytes, which accorded to linear square model. (authors)

The efficacy of hyperbaric oxygen in modifying the response of tissue to irradiation in doses of 200-400 rad per fraction

International Nuclear Information System (INIS)

Suit, D.D.; Orsi, L.

1975-01-01

The efficacy of respiration of O 2 at 30 psi in modifying the response of normal and tumour tissue to irradiation administered at 200 to 400 rad per fraction to anaesthetized mice has been evaluated. End-points have been delay in growth and TCD 50 for an early generation iso-transplant of a C 3 H mouse mammary carcinoma, and the acute reaction of skin of the C 3 H/Sed mouse. Results showed that the ratios of dose (air)/dose (O 2 30 psi) to elicit these end points were in the range 1.2 to 1.4. In earlier work using the same end points but doses per fraction 430 to 2100 rad, the ratios were 1.6 to 1.8. That is, for these tissue responses, respiration of O 2 at 30 psi increases the response of both normal and tumour tissue to all radiation doses tested. It is of greater effectiveness when combined with large doses per fraction, eg. greater than 430 rad. (author)

Gamma radiation-induced Impairment of hippocampal neurogenesis, comparison of single and fractionated dose regimens

International Nuclear Information System (INIS)

Khoshbin khoshnazar, A. R; Jahanshahi, M; Azami, N. S

2012-01-01

Radiation therapy of the brain is associated with many consequences, including cognitive disorders. Pathogenesis of radiation induced cognitive disorder is not clear, but reduction of neurogenesis in hippocampus may be an underlying reason. 24 adult male rats entered to study. Radiation absorbed dose to midbrain was 10 Gy, delivered by routine cobalt radiotherapy machine which its output was measured 115.24 cGy/min. The rats were divided in four groups of sixes, including groups of control, single fraction 10 Gy, fractionated 10 Gy and finally anaesthesia sham group. Number of pyramidal nerve cells was counted in two regions of hippocampus formation (CA1 and CA3). The radiation could reduce the number of cells in two regions of hippocampus significantly (p=0.000). It seems fractionated 10 Gy irradiation to more efficient than single fraction, while role of anaesthesia drug should be cautiously assessed. Moreover the rate of neurogenesis reduction was determined the same in these regions of hippocampus meaning the same radiosensitivity of cells

Modelling the variation in rectal dose due to inter-fraction rectal wall deformation in external beam prostate treatments

International Nuclear Information System (INIS)

Booth, Jeremy; Zavgorodni, Sergei

2005-01-01

Prostate radiotherapy inevitably deposits radiation dose in the rectal wall, and the dose delivered to prostate is limited by the expected rectal complications. Accurate evaluation of the rectal dose is non-trivial due to a number of factors. One of these is variation of the shape and position of the rectal wall (with respect to the clinical target volume (CTV)), which may differ daily from that taken during planning CT acquisition. This study uses data currently available in the literature on rectal wall motion to provide estimates of mean population rectal wall dose. The rectal wall geometry is characterized by a population mean radius of the rectum as well as inter-patient and inter-fraction standard deviations in rectum radius. The model is used to evaluate the range of inter-fraction and inter-patient rectal dose variations. The simulation of individual patients with full and empty rectum in the planning CT scan showed that large variations in rectal dose (>15 Gy) are possible. Mean calculated dose accounting for treatment and planning uncertainties in the rectal wall surface was calculated as well as the map of planning dose over/underpredictions. It was found that accuracy of planning dose is dependent on the CTV-PTV margin size with larger margins producing more accurate estimates. Over a patient population, the variation in rectal dose is reduced by increasing the number of pre-treatment CT scans

Impact of radiation technique, radiation fraction dose, and total cisplatin dose on hearing. Retrospective analysis of 29 medulloblastoma patients

Energy Technology Data Exchange (ETDEWEB)

Scobioala, Sergiu; Kittel, Christopher; Ebrahimi, Fatemeh; Wolters, Heidi; Eich, Hans Theodor [University Hospital of Muenster, Department of Radiotherapy and Radiooncology, Muenster (Germany); Parfitt, Ross; Matulat, Peter; Am Zehnhoff-Dinnesen, Antoinette [University Hospital of Muenster, Department of Phoniatrics and Pediatric Audiology, Muenster (Germany)

2017-11-15

To analyze the incidence and degree of sensorineural hearing loss (SNHL) resulting from different radiation techniques, fractionation dose, mean cochlear radiation dose (D{sub mean}), and total cisplatin dose. In all, 29 children with medulloblastoma (58 ears) with subclinical pretreatment hearing thresholds participated. Radiotherapy (RT) and cisplatin had been applied sequentially according to the HIT MED Guidance. Audiological outcomes up to the latest follow-up (median 2.6 years) were compared. Bilateral high-frequency SNHL was observed in 26 patients (90%). No significant differences were found in mean hearing threshold between left and right ears at any frequency. A significantly better audiological outcome (p < 0.05) was found after tomotherapy at the 6 kHz bone-conduction threshold (BCT) and left-sided 8 kHz air-conduction threshold (ACT) than after a combined radiotherapy technique (CT). Fraction dose was not found to have any impact on the incidence, degree, and time-to-onset of SNHL. Patients treated with CT had a greater risk of SNHL at high frequencies than tomotherapy patients even though D{sub mean} was similar. Increase in severity of SNHL was seen when the total cisplatin dose reached above 210 mg/m{sup 2}, with the highest abnormal level found 8-12 months after RT regardless of radiation technique or fraction dose. The cochlear radiation dose should be kept as low as possible in patients who receive simultaneous cisplatin-based chemotherapy. The risk of clinically relevant HL was shown when D{sub mean} exceeds 45 Gy independent of radiation technique or radiation regime. Cisplatin ototoxicity was shown to have a dose-dependent effect on bilateral SNHL, which was more pronounced in higher frequencies. (orig.) [German] Analyse von Inzidenz und Schweregrad einer sensorineuralen Schwerhoerigkeit (''sensorineural hearing loss'', SNHL) infolge der Wirkung unterschiedlicher Bestrahlungstechniken, Fraktionierungen, mittlerer

Optimum radiotherapy schedule for uterine cervical cancer based-on the detailed information of dose fractionation and radiotherapy technique

International Nuclear Information System (INIS)

Cho, Jae Ho; Kim, Hyun Chang; Suh, Chang Ok

2005-01-01

The best dose-fractionation regimen of the definitive radiotherapy for cervix cancer remains to be clearly determined. It seems to be partially attributed to the complexity of the affecting factors and the lack of detailed information on external and intra-cavitary fractionation. To find optimal practice guidelines, our experiences of the combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) were reviewed with detailed information of the various treatment parameters obtained from a large cohort of women treated homogeneously at a single institute. The subjects were 743 cervical cancer patients (Stage IB 198, IIA 77, IIB 364, IIIA 7, IIIB 89 and IVA 8) treated by radiotherapy alone, between 1990 and 1996. A total external beam radiotherapy (EBRT) dose of 23.4 ∼ 59.4 Gy (Median 45.0) was delivered to the whole pelvis. High-dose-rate intracavitary brachytherapy (HDR-ICBT) was also performed using various fractionation schemes. A Midline block (MLB) was initiated after the delivery of 14.4∼ 43.2 Gy (Median 36.0) of EBRT in 495 patients, while in the other 248 patients EBRT could not be used due to slow tumor regression or the huge initial bulk of tumor. The point A, actual bladder and rectal doses were individually assessed in all patients. The biologically effective dose (BED) to the tumor (α / β = 10) and late-responding tissues (α /β = 3) for both EBRT and HDR-ICBT were calculated. The total BED values to point A, the actual bladder and rectal reference points were the summation of the EBRT and HDR-ICBT. In addition to all the details on dose-fractionation, the other factors (i.e. the overall treatment time, physicians preference) that can affect the schedule of the definitive radiotherapy were also thoroughly analyzed. The association between MD-BED Gy 3 and the risk of complication was assessed using serial multiple logistic regressions models. The associations between R-BED Gy 3 and rectal complications

SU-F-T-01: Optimization of the Accelerated Partial Breast Brachytherapy Fractionation with Consideration of Physical Doses to Tumor and Organ at Risk

Energy Technology Data Exchange (ETDEWEB)

Fu, W; Huq, M [University of Pittsburgh Cancer Institute Pittsburgh, PA (United States)

2016-06-15

Purpose: The accelerated partial breast irradiation (APBI) with brachytherapy prescribes 34Gy to be delivered in 10 fractions over 5 consecutive working days without considering the physical dose to the target and organs at risk (OARs) for an individual patient. The purpose of this study is to optimize the fractionation scheme by evaluating the radiation effect on tumor and OARs with a modified linear-quadratic (LQ) model based on dose-volume histograms (DVHs). Methods: Five breast patients treated with multilumen balloon brachytherapy were selected. The minimum skin and rib spacing were ranged from 2.5mm to 14.3mm and from 1.0mm to 25.0mm, respectively. The LQ model parameters were set as: (1) breast: α=0.08, β=0.028, doubling time Tpot=14.4 days, and starting time Tk=21days; (2) skin: acute reaction α=0.101, β=0.009; late reaction α=0.064, β=0.029; (3) rib: α=0.3, β=0.12. Boundary dose Dt was 6 Gy for both target and OARs. The relation between radiation effects on the tumor (ET) and OARs (EOAR) were plotted for fraction number from 1 to 20. Results: The value of radiation effect from routine 3.4Gyx10 fractions was used as reference, ETref and EOARref. If set ET=ETref, the fractionation that results in minimum EOAR values correspond to the optimal fractionation. For these patients, the optimal numbers are 10 fractions for skin acute reaction, 18 fractions for skin and rib late reaction while the doses per fraction are 3.4Gy and 2.05–2.10Gy, respectively. If set EOAR=EOARref, the fractionation that results in a maximum ET value corresponds to the optimal fractionation. The optimal fractionation is 3.4Gyx10 fractions for skin acute reaction, and 2.10–2.25Gyx18 fractions for skin late reaction and rib. Conclusion: For APBI brachytherapy, the routine 3.4Gyx10 fractions is optimal fractionation for skin acute reaction, while 2.05–2.25Gyx18 fractions is optimal fractionation for late reaction of skin and rib.

Acute hematological tolerance to multiple fraction, whole body, low dose irradiation in an experimental murine system

International Nuclear Information System (INIS)

Melamed, J.S.; Chen, M.G.; Brown, J.W.; Katagiri, C.A.

1980-01-01

Using a dose fractionation scheme patterned after the current regimen for treatment of disseminated non-Hodgkin lymphoma, the authors studied the effects of irradation on progenitor and effector cells for hematopoiesis in five-month-old BC3F 1 mice. Fractions of 20 or 50 rad (0.2 or 0.5 Gy) total body irradation were given twice weekly to a final total dose of 200 or 500 rad (2 or 5 Gy), respectively. Weekly assays revealed a marked, sustained depression of stem cell activity, measured as numbers of spleen colony-forming units (CFU-S) and in vitro colony-forming cells (CFU-C), without corresponding depression of effector cells (red and white cells, and platelets). The lack of correlation between numbers of stem cells and peripheral elements is relevant to clinical assessment of marrow reserve

The influence of dose per fraction on the pathogenesis of radiation nephropathy

Energy Technology Data Exchange (ETDEWEB)

Yildiz, F.; Atahan, I.L.; Tuncel, M.; Konan, A. [Hacettepe University, Faculty of Medicine, Ankara (Turkey). Departments of Radiation Oncology and Anatomy

1998-11-01

Both kidneys of male Wistar rats were irradiated with either a 1 0-Gy single dose or 26 Gy at a rate of 2 Gy per fraction per day. Serum blood urea nitrogen (BUN), creatinine and blood haematocrit levels were assessed prior to radiotherapy and at intervals of 8 weeks thereafter. A subset of animals from each dose group were killed at 4, 8,16 and 24 weeks and both kidneys of each animal were examined by electron microscopy. In both dose groups a significant increase in BUN and creatinine levels, together with a decrease in haematocrit level, was observed at 16 weeks, and this was followed by an apparent improvement at 24 weeks. There was no statistical difference in these responses between the two groups. The morphological changes in both dose groups were essentially similar, but differed in severity. At 4 weeks after irradiation glomerular and proximal tubular injury were observed in both groups. A marked increase of glomerular and tubular injury in the 10-Gy dose group, without any apparent progression in the 26-Gy dose group, was detected at 8 weeks. By 16 weeks a noticeable improvement in both tubular and glomerular lesions (especially in the 10-Gy dose group) was observed. No apparent difference from the 16th week of evaluation was found at 24 weeks. These findings indicate that there is some recovery in kidney after irradiation, but the extent of the recovery process is somewhat limited. Copyright (1998) Blackwell Science Pty Ltd 38 refs., 1 tab., 4 figs.

Radiobiological basis of total body irradiation with different dose rate and fractionation: repair capacity of hemopoietic cells

International Nuclear Information System (INIS)

Song, C.W.; Kim, T.H.; Khan, F.M.; Kersey, J.H.; Levitt, S.H.

1981-01-01

Total body irradiation (TBI) followed by bone marrow transplantation is being used in the treatment of malignant or non-malignant hemopoietic disorders. It has been believed that the ability of hemopoietic cells to repair sublethal radiation damage is negligible. Therefore, several schools of investigators suggested that TBI in a single exposure at extremely low dose rate (5 rad/min) over several hours, or in several fractions in 2-3 days, should yield a higher therapeutic gain, as compared with a single exposure at a high dose rate (26 rad/min). We reviewed the existing data in the literature, in particular, the response of hemopoietic cells to fractionated doses of irradiation and found that the repair capacity of both malignant and non-malignant hemopoietic cells might be greater than has been thought. It is concluded that we should not underestimate the ability of hemopoietic cells to repair sublethal radiation damage in using TBI

Comparison of patient-reported acute urinary and sexual toxicity scores in a 6- versus 2-fraction course of high-dose-rate prostate brachytherapy monotherapy

International Nuclear Information System (INIS)

Ragab, Omar; Park, Sang-June; Zhang, Mingle; Wang, Jason; Velez, Maria; Demanes, David J.; Banerjee, Robyn; Patel, Shyamal; Kamrave, Mitchell

2018-01-01

To identify differences in acute urinary and sexual toxicity between a 6-fraction and 2-fraction high-dose-rate brachytherapy monotherapy regimen and correlate dosimetric constraints to short-term toxicity. A single institution retrospective study of 116 men with prostate cancer treated with HDR monotherapy from 2010 to 2015 was conducted. Eighty-one men had 7.25 Gy × 6-fractions and 35 men had 13.5 Gy × 2-fractions. Patients had two CT-planned implants spaced 1–2 weeks apart. Patient baseline characteristics, International Prostate Symptom Scores (IPSS) and Sexual Health Inventory for Men (SHIM) scores were collected pre-treatment and 3, 6 and 12 months post-implantation. Mixed effect modelling was undertaken to compare baseline, 1–6 month and 7–12 month scores between groups. Poisson regression analysis was performed to correlate dosimetric constraints with acute toxicity. There was no difference between baseline and post-implantation IPSS scores between 6-fraction and 2-fraction groups. SHIM scores for men treated with 6-fractions had a steeper decline at 1–6 months, but resolved at 7–12 months. Pre-treatment alpha-blocker use correlated with worse short-term acute urinary toxicity. Worsened SHIM score correlated with increasing age, diabetes mellitus and androgen-deprivation therapy. In a dosimetric analysis of outcomes, prostate V150 dose and bladder wall (D01.cc, D1cc, D2cc) dose correlated with increased IPSS score. No increased acute genitourinary or sexual dysfunction has been observed in men when transitioning from 6-fraction to 2-fraction HDR monotherapy. A dosimetric correlation was found between the V150 and bladder wall doses for acute urinary toxicity. Future research should continue to standardize and validate dose constraints for prostate HDR monotherapy patients.

SU-F-T-516: Effects of Inter-Fraction Organ Displacement/deformation On the Delivered Doses to the Heart, Esophagus, and Lungs in Patients Receiving Thoracic Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Hammers, J; Matney, J; Kaidar-Person, O; Zagar, T; Marks, L; Das, S; Mavroidis, P [University North Carolina, Chapel Hill, NC (United States)

2016-06-15

Purpose: To quantitatively assess the effects of inter-fraction changes in organ shape and location on the delivered dose distribution to the organs at risk (OAR) in lung cancer patients. Methods: This study analyzes treatment data of 10 patients, who were treated to 60Gy in 30 fractions. In each fraction a cone beam CT (CBCT) was acquired. Each CBCT was registered with the planning CT using deformable registration tools within MIM Software. The daily setup shifts were used to translate the planned dose distribution on the deformed planning CT. The structures of lungs, esophagus and heart were re-delineated by a physician on each CBCT. The doses delivered to each OAR, reflecting changes in the position and shape variations, were recomputed. Resultant daily dose volume histograms (DVHs) for OARs were computed and compared to those from the planning CT. Results: Based on the findings of two patients and 24 CBCTs analyzed so far, higher doses are delivered to the lungs and esophagus compared to the treatment plan. The dose differences per fraction between the delivered doses and those in the treatment plan are: for patient 1, lung mean dose = 5.3±1.3cGy and esophagus mean dose = 3.4±3.5cGy. For patient 2, lung mean dose = 12.0±3.9cGy and esophagus mean dose = 34.2±7.5cGy. Regarding the maximum dose to heart, the results varied (−18.9±22.0cGy for patient1 and 53.0±62.2cGy for patient2). Conclusion: The dosimetric effects of inter-fractional anatomical variations could be estimated using deformable image registration and manual organ segmentation for each CBCT. A considerable dose distribution variation between fractions was observed for the OARs. These changes are currently not taken into account while treating the patients and these may explain cases with severe side effects even when the treatment plan looks satisfactory. These results suggest the need for automated daily dose tracking and accumulation.

First trial of spatial and temporal fractionations of the delivered dose using synchrotron microbeam radiation therapy

International Nuclear Information System (INIS)

Serduc, Raphael; Braeuer-Krisch, Elke; Bouchet, Audrey; Brochard, Thierry; Bravin, Alberto; Le Duc, Geraldine; Renaud, Luc; Laissue, Jean Albert

2009-01-01

The technical feasibility of temporal and spatial fractionations of the radiation dose has been evaluated using synchrotron microbeam radiation therapy for brain tumors in rats. A significant increase in lifespan (216%, p<0.0001) resulted when three fractions of microbeam irradiation were applied to the tumor through three different ports, orthogonal to each other, at 24 h intervals. However, there were no long-term survivors, and immunohistological studies revealed that 9 L tumors were not entirely ablated. (orig.)

First trial of spatial and temporal fractionations of the delivered dose using synchrotron microbeam radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Serduc, Raphael [Toulouse Univ. (France). UPS Centre de Recherche Cerveau et Cognition; CNRS, CerCo, Toulouse (France); European Synchrotron Radiation Facility, 38 - Grenoble (France); Braeuer-Krisch, Elke; Bouchet, Audrey; Brochard, Thierry; Bravin, Alberto; Le Duc, Geraldine [European Synchrotron Radiation Facility, 38 - Grenoble (France); Renaud, Luc [Toulouse Univ. (France). UPS Centre de Recherche Cerveau et Cognition; CNRS, CerCo, Toulouse (France); Laissue, Jean Albert [Bern Univ. (Switzerland). Inst. of Pathology

2009-07-15

The technical feasibility of temporal and spatial fractionations of the radiation dose has been evaluated using synchrotron microbeam radiation therapy for brain tumors in rats. A significant increase in lifespan (216%, p<0.0001) resulted when three fractions of microbeam irradiation were applied to the tumor through three different ports, orthogonal to each other, at 24 h intervals. However, there were no long-term survivors, and immunohistological studies revealed that 9 L tumors were not entirely ablated. (orig.)

Optimization of the temporal pattern of applied dose for a single fraction of radiation: Implications for radiation therapy

Science.gov (United States)

Altman, Michael B.

The increasing prevalence of intensity modulated radiation therapy (IMRT) as a treatment modality has led to a renewed interest in the potential for interaction between prolonged treatment time, as frequently associated with IMRT, and the underlying radiobiology of the irradiated tissue. A particularly relevant aspect of radiobiology is cell repair capacity, which influences cell survival, and thus directly relates to the ability to control tumors and spare normal tissues. For a single fraction of radiation, the linear quadratic (LQ) model is commonly used to relate the radiation dose to the fraction of cells surviving. The LQ model implies a dependence on two time-related factors which correlate to radiobiological effects: the duration of radiation application, and the functional form of how the dose is applied over that time (the "temporal pattern of applied dose"). Although the former has been well studied, the latter has not. Thus, the goal of this research is to investigate the impact of the temporal pattern of applied dose on the survival of human cells and to explore how the manipulation of this temporal dose pattern may be incorporated into an IMRT-based radiation therapy treatment planning scheme. The hypothesis is that the temporal pattern of applied dose in a single fraction of radiation can be optimized to maximize or minimize cell kill. Furthermore, techniques which utilize this effect could have clinical ramifications. In situations where increased cell kill is desirable, such as tumor control, or limiting the degree of cell kill is important, such as the sparing of normal tissue, temporal sequences of dose which maximize or minimize cell kill (temporally "optimized" sequences) may provide greater benefit than current clinically used radiation patterns. In the first part of this work, an LQ-based modeling analysis of effects of the temporal pattern of dose on cell kill is performed. Through this, patterns are identified for maximizing cell kill for a

Effect of the supply dose on the 15N enrichment level of cow's milk nitrogenous fractions

International Nuclear Information System (INIS)

Colin, O.; Laurent, F.; Vignon, B.; Antoine, J.M.

1994-01-01

Production of cow milk 15 N-labelled proteins is necessary for the study of their digestion by man. An adequate enrichment is required for compatibility with utilization constraints (application dose, studied fractions...). A test was conducted with five cows in order to optimize the utilization of labelled ammonium sulphate in the cow diet for 15 N enrichment of the milk nitrogenous matter. Doses and supply timing of labelled compounds are discussed. 3 figs., 3 refs

Dose escalation by hypo fractionation in localized prostate cancer - a large single institution experience

International Nuclear Information System (INIS)

Mahadevan, A.; Klein, E.; Kupelian, P.

2003-01-01

To report the outcomes of high dose radiation therapy using Intensity Modulated Radiation Therapy (IMRT) with hypo fractionation in localized prostate cancer at the Cleveland Clinic Foundation. A total of 278 patients with localized prostate cancer were treated with IMRT between 1998 and 2001. All cases had available pretreatment PSA (iPSA) and biopsy Gleason scores (bGS), no nodal metastasis, a minimum 2 year follow-up, and >5 follow-up PSA levels. The frequency by T-stage was: T1-T2A in 86%, T2B-T2C in 9%, and T3 in 5%. The median iPSA was 8.35. The frequency by bGS was: =7 in 45%. The age range for the patients was from 48 to 85 years (median 68 years). The median follow-up was 33 months (range: 24-49 months). The median doses delivered were 83Gy (delivered at 2.5Gy per fraction to 70 Gy; this being equivalent to 83 Gy at standard fractionation of 1.8 Gy using an alpha/beta of 2). The ASTRO definition for biochemical failure was used. Toxicity was assessed using Radiation Therapy Oncology Group (RTOG) criteria. The 3-year biochemical relapse free survival (bRFS) for the entire cohort at three years was 91%. Any (grade 1 or higher) acute genito-urinary (GU) side effects were seen in 79% of patients. Grade 2 or higher acute GU toxicity was seen in 18% of patients. Any (grade 1 or higher) acute gastro-intestinal (GI) side effects were seen in 65% of patients. Grade 2 or higher acute GI toxicity was seen in 11% of patients. Any (grade 1 or higher) late GU side effects were seen in 3% of patients. Grade 2 or higher late GU toxicity was seen in 1.5% of patients. Any (grade 1 or higher) late GI side effects were seen in 13% of patients. Grade 2 or higher late GI toxicity was seen in 5% of patients. Higher doses of radiation delivered by IMRT resulted in excellent bRFS outcomes in patients with localized prostate cancer receiving external beam radiation therapy. IMRT can be effectively used to safely increase dose delivery without compromising on quality of life

SU-E-J-176: Characterization of Inter-Fraction Breast Variability and the Implications On Delivered Dose

Energy Technology Data Exchange (ETDEWEB)

Sudhoff, M; Lamba, M; Kumar, N; Ward, A; Elson, H [University of Cincinnati, Cincinnati, OH (United States)

2015-06-15

Purpose: To systematically characterize inter-fraction breast variability and determine implications on delivered dose. Methods: Weekly port films were used to characterize breast setup variability. Five evenly spaced representative positions across the contour of each breast were chosen on the electronic port film in reference to graticule, and window and level was set such that the skin surface of the breast was visible. Measurements from the skin surface to treatment field edge were taken on each port film at each position and compared to the planning DRR, quantifying the variability. The systematic measurement technique was repeated for all port films for 20 recently treated breast cancer patients. Measured setup variability for each patient was modeled as a normal distribution. The distribution was randomly sampled from the model and applied as isocentric shifts in the treatment planning computer, representing setup variability for each fraction. Dose was calculated for each shifted fraction and summed to obtain DVHs and BEDs that modeled the dose with daily setup variability. Patients were categorized in to relevant groupings that were chosen to investigate the rigorousness of immobilization types, treatment techniques, and inherent anatomical difficulties. Mean position differences and dosimetric differences were evaluated between planned and delivered doses. Results: The setup variability was found to follow a normal distribution with mean position differences between the DRR and port film between − 8.6–3.5 mm with sigma range of 5.3–9.8 mm. Setup position was not found to be significantly different than zero. The mean seroma or whole breast PTV dosimetric difference, calculated as BED, ranged from a −0.23 to +1.13Gy. Conclusion: A systematic technique to quantify and model setup variability was used to calculate the dose in 20 breast cancer patients including variable setup. No statistically significant PTV or OAR BED differences were found between

Second Study of Hyper-Fractionated Radiotherapy

Directory of Open Access Journals (Sweden)

R. Jacob

1999-01-01

Full Text Available Purpose and Method. Hyper-fractionated radiotherapy for treatment of soft tissue sarcomas is designed to deliver a higher total dose of radiation without an increase in late normal tissue damage. In a previous study at the Royal Marsden Hospital, a total dose of 75 Gy using twice daily 1.25 Gy fractions resulted in a higher incidence of late damage than conventional radiotherapy using 2 Gy daily fractions treating to a total of 60 Gy. The current trial therefore used a lower dose per fraction of 1.2 Gy and lower total dose of 72 Gy, with 60 fractions given over a period of 6 weeks.

Scattered fractions of dose from 18 and 25 MV X-ray radiotherapy linear accelerators

International Nuclear Information System (INIS)

Shobe, J.; Rodgers, J.E.; Taylor, P.L.; Jackson, J.; Popescu, G.

1996-01-01

Over the years, measurements have been made at a few energies to estimate the scattered fraction of dose from the patient in medical radiotherapy operations. This information has been a useful aid in the determination of shielding requirements for these facilities. With these measurements, known characteriztics of photons, and various other known parameters, Monte Carlo codes are being used to calculate the scattered fractions and hence the shielding requirements for the photons of other energies commonly used in radiotherapeutic applications. The National Institute of Standards and Technology (NIST) acquired a Sagittaire medical linear accelerator (linac) which was previously located at the Yale-New Haven Hospital. This linac provides an X-ray beam of 25 MV photons and electron beams with energies up to 32 MeV. The housing on the gantry was permanently removed from the accelerator during installation. A Varian Clinac 1800 linear accelerator was used to produce the 18 MV photons at the Frederick Memorial Hospital Regional Cancer Therapy Center in Frederick, MD. This paper represents a study of the photon dose scattered from a patient in typical radiation treatment situations as it relates to the dose delivered at the isocenter in water. The results of these measurements will be compared to Monte Carlo calculations. Photon spectral measurements were not made at this time. Neutron spectral measurements were made on this Sagittaire machine in its previous location and that work was not repeated here, although a brief study of the neutron component of the 18 and 25 MV linacs was performed utilizing thermoluminescent dosimetry (TLD) to determine the isotropy of the neutron dose. (author)

Estimation of dependence between mean of fractionation of photons and neutrons dose and intensity of post-irradiation reaction of mouse large intestine

International Nuclear Information System (INIS)

Gasinska, A.

1995-01-01

The aim of the work was verification of mouse large intestine tolerance on fractionated 250 kV X-rays and 2.3 MeV neutrons doses. Two cm of large intestine of mouse CBA/HT strain were irradiated with various fraction doses: from 0.25 to 35 Gy of X-rays and 0.05-12 Gy of neutrons. The measure of injury was handicap of intestine function. Early post-irradiation reaction was measured by loss of body weight (2-3 weeks after irradiation) and mouse mortality (till 2 months after irradiation, LD50/2). The late reaction was measured on the base of maximal body weight in 1 year period after irradiation, deformation of excrements (after 10 months) and death of animals (till 12. month after irradiation, LD50/12). Fractionation of X-ray dose influenced on decrease of intensification of late irradiation effects. After fractionation of neutrons this effect has not been observed. α/β coefficient for X-rays was 19.9 Gy [15.2; 27.0] for body weight nadir, 13.4 Gy [9.3; 19.5] for early mortality (LD50/2), 6.4 Gy [3.6;11.0] for maximal body weight and 6.9 [4.2; 10.8] for late mortality (LD50/12). Analysis of influence of low doses of photons 90.25-4 Gy) and neutrons (0.05-0.8 Gy) showed trend to reduction α/β for photons only (LD50/2=5.4 Gy; LD50/12=4.6 Gy). α/β coefficient for neutrons was defined by LQ model only for maximal body weight and was 19.9 Gy [9.5; 61.0]. In application of graphic method α/β for neutrons was 230 Gy for early and 48 Gy for late effects. Lower values of α/β coefficient for late irradiation effects for photon radiation demonstrate the big influence of fractionation of photons dose on large intestine tolerance (decrease intensity in all biological effects). Author did not observe increase of intestine tolerance in fractionation of neutrons dose. Effect of irradiation damages repair in interfraction pauses, measured by percent of regenerated dose (F r ) was much bigger for photons. For X-rays it was 50% for early and 63% for late effects. In case of

Low-dose fractionated whole-body irradiation in the treatment of advanced non-Hodgkin's lymphoma

International Nuclear Information System (INIS)

Choi, N.C.; Timothy, A.R.; Kaufman, S.D.; Carey, R.W.; Aisenberg, A.C.

1979-01-01

Thirty-nine patients with advanced non-Hodgkin's lymphoma (38 patients with lymphocytic lymphoma and 1 patient with mixed lymphocytic and histiocytic lymphoma) were treated by fractionated low dose whole body irradiation (WBI) with a minimum follow-up of 8 months. Twenty-eight patients had no previous treatment and the other 11 patients were in relapse after previous chemotherapy or regional radiotherapy. There were 20 and 19 patients in stages III and IV groups, respectively. The majority of patients (31) had nodular histology; diffuse lymphocytic lymphoma was present in 8 patients (Rappaport criteria) (9). Constitutional symptoms were present in 10 patients. Thirty-three (85%) attained complete remission (CR) with median duration of remission 24 months. Actuarial survival was 78% and 74% at 3 and 4 years. However, relapse free survival was 26% at 3 and 4 years. A prospective randomized trial to compare 10 vs. 15 rad per fraction of fractionated WBI schedules (the same total dose 150 rad) demonstrated no difference in response rate, response duration, and median nadir platelet or WBC counts between the two schedules. Supplement radiotherapy to bulky tumor site prevented local recurrence, but did not influence survival or duration or remission. Major toxicity was thrombocytopenia with median nadir platelet counts 77,000/mm 3 (11,000 to 170,000/mm 3 ). Five of 6 patients with diffuse lymphocytic poorly differentiated lymphoma attained CR. However, their median survival was 30 months which is much shorter than that of nodular lymphoma. Constitutional symptoms and advanced stage (stage IV) were associated with shorter duration of remission. Response of patients in relapse after WBI to subsequent chemotherapy +- local radiotherapy was CR in 50% and PR in 40%. Fractionated whole body irradiation is an excellent systemic induction agent for advanced lymphocytic and mixed lymphoma

Molecular mechanisms involved in modulation of p-glycoprotein expression from squamous cell carcinoma by low dose fractionated radiation (LDFR)

International Nuclear Information System (INIS)

Shajahan; Shahin; Shareef, Mohammed M.; Sathishkumar, Sabapathi; Mohiuddin, Mohammed; Ahmed, Mansoor M.; Brown, Brandee C.; Jones, Raleigh; Spring, Paul M.

2004-01-01

In the present study, two squamous cell carcinoma oral cavity cells (SCCOC), T-167 (p53 wild type) and T-409 (p53 mutant), were exposed to either clinically relevant dose (2 Gy), high dose (7Gy) or fractionated low dose (LDFR) (0.5 Gy x 4) and the expression of Mdr1 gene was assessed by real time RT-PCR, semiquantitative 32 P RT-PCR and luciferase reporter assay

A framework to measure myocardial extracellular volume fraction using dual-phase low dose CT images

International Nuclear Information System (INIS)

Liu, Yixun; Summers, Ronald M.; Yao, Jianhua; Liu, Songtao; Sibley, Christopher T.; Bluemke, David A.; Nacif, Marcelo S.

2013-01-01

Purpose: Myocardial extracellular volume fraction (ECVF) is a surrogate imaging biomarker of diffuse myocardial fibrosis, a hallmark of pathologic ventricular remodeling. Low dose cardiac CT is emerging as a promising modality to detect diffuse interstitial myocardial fibrosis due to its fast acquisition and low radiation; however, the insufficient contrast in the low dose CT images poses great challenge to measure ECVF from the image. Methods: To deal with this difficulty, the authors present a complete ECVF measurement framework including a point-guided myocardial modeling, a deformable model-based myocardium segmentation, nonrigid registration of pre- and post-CT, and ECVF calculation. Results: The proposed method was evaluated on 20 patients by two observers. Compared to the manually delineated reference segmentations, the accuracy of our segmentation in terms of true positive volume fraction (TPVF), false positive volume fraction (FPVF), and average surface distance (ASD), were 92.18% ± 3.52%, 0.31% ± 0.10%, 0.69 ± 0.14 mm, respectively. The interobserver variability measured by concordance correlation coefficient regarding TPVF, FPVF, and ASD were 0.95, 0.90, 0.94, respectively, demonstrating excellent agreement. Bland-Altman method showed 95% limits of agreement between ECVF at CT and ECVF at MR. Conclusions: The proposed framework demonstrates its efficiency, accuracy, and noninvasiveness in ECVF measurement and dramatically advances the ECVF at cardiac CT toward its clinical use

A framework to measure myocardial extracellular volume fraction using dual-phase low dose CT images

Energy Technology Data Exchange (ETDEWEB)

Liu, Yixun; Summers, Ronald M.; Yao, Jianhua, E-mail: JYao@cc.nih.gov [Clinical Image Processing Service, Radiology and Imaging Sciences, NIH Clinical Center, Bethesda, Maryland 20892 (United States); Liu, Songtao; Sibley, Christopher T.; Bluemke, David A. [Radiology and Imaging Sciences, NIH Clinical Center, Bethesda, Maryland 20892-1182 and Molecular Biomedical Imaging Laboratory, National Institute of Biomedical Imaging and Bioengineering, NIH Clinical Center, Bethesda, Maryland 20892 (United States); Nacif, Marcelo S. [Radiology and Imaging Sciences, NIH Clinical Center, Bethesda, Maryland 20892-1182 (United States)

2013-10-15

Purpose: Myocardial extracellular volume fraction (ECVF) is a surrogate imaging biomarker of diffuse myocardial fibrosis, a hallmark of pathologic ventricular remodeling. Low dose cardiac CT is emerging as a promising modality to detect diffuse interstitial myocardial fibrosis due to its fast acquisition and low radiation; however, the insufficient contrast in the low dose CT images poses great challenge to measure ECVF from the image. Methods: To deal with this difficulty, the authors present a complete ECVF measurement framework including a point-guided myocardial modeling, a deformable model-based myocardium segmentation, nonrigid registration of pre- and post-CT, and ECVF calculation. Results: The proposed method was evaluated on 20 patients by two observers. Compared to the manually delineated reference segmentations, the accuracy of our segmentation in terms of true positive volume fraction (TPVF), false positive volume fraction (FPVF), and average surface distance (ASD), were 92.18% ± 3.52%, 0.31% ± 0.10%, 0.69 ± 0.14 mm, respectively. The interobserver variability measured by concordance correlation coefficient regarding TPVF, FPVF, and ASD were 0.95, 0.90, 0.94, respectively, demonstrating excellent agreement. Bland-Altman method showed 95% limits of agreement between ECVF at CT and ECVF at MR. Conclusions: The proposed framework demonstrates its efficiency, accuracy, and noninvasiveness in ECVF measurement and dramatically advances the ECVF at cardiac CT toward its clinical use.

Fractionated irradiation and haematopoiesis. Pt. 3

International Nuclear Information System (INIS)

Ninkov, V.; Karanovic, D.; Savovski, K.

1982-01-01

The effect of total single fractionated irradiation with short time interval on heamatopoietic regeneration of the bone marrow and spleen was investigated. Also, the importance of first dose, when dose of 600 R was divided in two unequal fractions with time interval of 300 s was studied. The investigation was performed on 25 day old rats. The dose of 600 R (X-rays) was divided on: 500 + 100, 400 + 200, 300 + 300, 200 + 400 or 100 + 500 R with time interval of 150, 300 or 600 s. Ten days after irradiation the changes in blood, bone marrow and spleen were observed. After unequal fractionated dose with interval of 600 s slight effect was found. The results after intervals of 600 s and 300 s were significant, when the total dose was divided in two equal doses. The first dose has no promoting role in haematopoietic regeneration when total dose was unequally fractionated. (orig.) [de

Fraction of a dose absorbed estimation for structurally diverse low solubility compounds.

Science.gov (United States)

Sugano, Kiyohiko

2011-02-28

The purpose of the present study was to investigate the prediction accuracy of the fully mechanistic gastrointestinal unified theoretical (GUT) framework for in vivo oral absorption of low solubility drugs. Solubility in biorelevant media, molecular weight, logP(oct), pK(a), Caco-2 permeability, dose and particle size were used as the input parameters. To neglect the effect of the low stomach pH on dissolution of a drug, the fraction of a dose absorbed (Fa%) of undissociable and free acids were used. In addition, Fa% of free base drugs with the high pH stomach was also included to increase the number of model drugs. In total twenty nine structurally diverse compounds were used as the model drugs. Fa% data at several doses and particle sizes in humans and dogs were collated from the literature (total 110 Fa% data). In approximately 80% cases, the prediction error was within 2 fold, suggesting that the GUT framework has practical predictability for drug discovery, but not for drug development. The GUT framework appropriately captured the dose and particle size dependency of Fa% as the particle drifting effect was taken into account. It should be noted that the present validation results cannot be applied for salt form cases and other special formulations such as solid dispersions and emulsion formulations. Copyright © 2010 Elsevier B.V. All rights reserved.

Maximizing Tumor Immunity With Fractionated Radiation

International Nuclear Information System (INIS)

Schaue, Dörthe; Ratikan, Josephine A.; Iwamoto, Keisuke S.; McBride, William H.

2012-01-01

Purpose: Technologic advances have led to increased clinical use of higher-sized fractions of radiation dose and higher total doses. How these modify the pathways involved in tumor cell death, normal tissue response, and signaling to the immune system has been inadequately explored. Here we ask how radiation dose and fraction size affect antitumor immunity, the suppression thereof, and how this might relate to tumor control. Methods and Materials: Mice bearing B16-OVA murine melanoma were treated with up to 15 Gy radiation given in various-size fractions, and tumor growth followed. The tumor-specific immune response in the spleen was assessed by interferon-γ enzyme-linked immunospot (ELISPOT) assay with ovalbumin (OVA) as the surrogate tumor antigen and the contribution of regulatory T cells (Tregs) determined by the proportion of CD4 + CD25 hi Foxp3 + T cells. Results: After single doses, tumor control increased with the size of radiation dose, as did the number of tumor-reactive T cells. This was offset at the highest dose by an increase in Treg representation. Fractionated treatment with medium-size radiation doses of 7.5 Gy/fraction gave the best tumor control and tumor immunity while maintaining low Treg numbers. Conclusions: Radiation can be an immune adjuvant, but the response varies with the size of dose per fraction. The ultimate challenge is to optimally integrate cancer immunotherapy into radiation therapy.

Effect of action of fractioned ionizing radiation in small dose on thyroid gland of rats

OpenAIRE

О. О. Prykhodko; V. V. Lizogubov; V. S. Usenko

2005-01-01

The effect of fractionated X-irradiation by 0.25 Gy dose to rat thyroid gland was studied . It was shown the decrease of thyrocyte proliferative activity that can induce the late effect of pathogenesis to thyroid land and biochemical pathways that control by thyroid hormones. Additional effect by any mutagenic factor may induce thyroid tumor development.

In vivo assessment of the gastric mucosal tolerance dose after single fraction, small volume irradiation of liver malignancies by computed tomography-guided, high-dose-rate brachytherapy

International Nuclear Information System (INIS)

Streitparth, Florian; Pech, Maciej; Boehmig, Michael; Ruehl, Ricarda; Peters, Nils; Wieners, Gero; Steinberg, Johannes; Lopez-Haenninen, Enrique; Felix, Roland; Wust, Peter; Ricke, Jens

2006-01-01

Purpose: The aim of this study was to assess the tolerance dose of gastric mucosa for single-fraction computed tomography (CT)-guided, high-dose-rate (HDR) brachytherapy of liver malignancies. Methods and Materials: A total of 33 patients treated by CT-guided HDR brachytherapy of liver malignancies in segments II and/or III were included. Dose planning was performed upon a three-dimensional CT data set acquired after percutaneous applicator positioning. All patients received gastric protection post-treatment. For further analysis, the contours of the gastric wall were defined in every CT slice using Brachyvision Software. Dose-volume histograms were calculated for each treatment and correlated with clinical data derived from questionnaires assessing Common Toxicity Criteria (CTC). All patients presenting symptoms of upper GI toxicity were examined endoscopically. Results: Summarizing all patients the minimum dose applied to 1 ml of the gastric wall (D 1ml ) ranged from 6.3 to 34.2 Gy; median, 14.3 Gy. Toxicity was present in 18 patients (55%). We found nausea in 16 (69%), emesis in 9 (27%), cramping in 13 (39%), weight loss in 12 (36%), gastritis in 4 (12%), and ulceration in 5 patients (15%). We found a threshold dose D 1ml of 11 Gy for general gastric toxicity and 15.5 Gy for gastric ulceration verified by an univariate analysis (p = 0.01). Conclusions: For a single fraction, small volume irradiation we found in the upper abdomen a threshold dose D 1ml of 15.5 Gy for the clinical endpoint ulceration of the gastric mucosa. This in vivo assessment is in accordance with previously published tolerance data

Fractional-Dose Inactivated Poliovirus Vaccine Campaign - Sindh Province, Pakistan, 2016.

Science.gov (United States)

Pervaiz, Aslam; Mbaeyi, Chukwuma; Baig, Mirza Amir; Burman, Ashley; Ahmed, Jamal A; Akter, Sharifa; Jatoi, Fayaz A; Mahamud, Abdirahman; Asghar, Rana Jawad; Azam, Naila; Shah, Muhammad Nadeem; Laghari, Mumtaz Ali; Soomro, Kamaluddin; Wadood, Mufti Zubair; Ehrhardt, Derek; Safdar, Rana M; Farag, Noha

2017-12-01

Following the declaration of eradication of wild poliovirus (WPV) type 2 in September 2015, trivalent oral poliovirus vaccine (tOPV) was withdrawn globally to reduce the risk for type 2 vaccine-derived poliovirus (VDPV2) transmission; all countries implemented a synchronized switch to bivalent OPV (type 1 and 3) in April 2016 (1,2). Any isolation of VDPV2 after the switch is to be treated as a potential public health emergency and might indicate the need for supplementary immunization activities (3,4). On August 9, 2016, VDPV2 was isolated from a sewage sample taken from an environmental surveillance site in Hyderabad, Sindh province, Pakistan. Possible vaccination activities in response to VDPV2 isolation include the use of injectable inactivated polio vaccine (IPV), which poses no risk for vaccine-derived poliovirus transmission. Fractional-dose, intradermal IPV (fIPV), one fifth of the standard intramuscular dose, has been developed to more efficiently manage limited IPV supplies. fIPV has been shown in some studies to be noninferior to full-dose IPV (5,6) and was used successfully in response to a similar detection of a single VDPV2 isolate from sewage in India (7). Injectable fIPV was used for response activities in Hyderabad and three neighboring districts. This report describes the findings of an assessment of preparatory activities and subsequent implementation of the fIPV campaign. Despite achieving high coverage (>80%), several operational challenges were noted. The lessons learned from this campaign could help to guide the planning and implementation of future fIPV vaccination activities.

Treatment results by uneven fractionated irradiation, low-dose rate telecobalt therapy as a boost, and intraoperative irradiation for malignant glioma

Energy Technology Data Exchange (ETDEWEB)

Yamada, Shogo; Takai, Yoshihiro; Nemoto, Kenji; Ogawa, Yoshihiro; Kakuto, Yoshihisa; Hoshi, Akihiko; Sakamoto, Kiyohiko; Kayama, Takamasa; Yoshimoto, Takashi (Tohoku Univ., Sendai (Japan). School of Medicine)

1992-08-01

The prognosis of malignant glioma is extremely poor. We applied conventionally fractionated irradiation combined with 1-(4-aminio-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), uneven fractionated irradiation with ACNU, low dose rate telecobalt therapy as a boost, and intraoperative irradiation against 110 malignant gliomas to investigate the efficacy of these methods as alternative treatments for malignant glioma. Although local tumor control by uneven fractionated irradiation was better than that by the other methods, no significant improvement was obtained in survival rates. As a result of multiple regression analysis, age and histology were major factors for survival rates, and the difference of treatment methods was not important. Both low-dose rate telecobalt therapy as a boost and intraoperative irradiation showed little advantage because of the high risk of brain necrosis associated with them. (author).

Immunogenicity of fractional doses of tetravalent a/c/y/w135 meningococcal polysaccharide vaccine: results from a randomized non-inferiority controlled trial in Uganda.

Directory of Open Access Journals (Sweden)

Philippe J Guerin

Full Text Available Neisseria meningitidis serogroup A is the main causative pathogen of meningitis epidemics in sub-Saharan Africa. In recent years, serogroup W135 has also been the cause of epidemics. Mass vaccination campaigns with polysaccharide vaccines are key elements in controlling these epidemics. Facing global vaccine shortage, we explored the use of fractional doses of a licensed A/C/Y/W135 polysaccharide meningococcal vaccine.We conducted a randomized, non-inferiority trial in 750 healthy volunteers 2-19 years old in Mbarara, Uganda, to compare the immune response of the full dose of the vaccine versus fractional doses (1/5 or 1/10. Safety and tolerability data were collected for all subjects during the 4 weeks following the injection. Pre- and post-vaccination sera were analyzed by measuring serum bactericidal activity (SBA with baby rabbit complement. A responder was defined as a subject with a > or =4-fold increase in SBA against a target strain from each serogroup and SBA titer > or =128. For serogroup W135, 94% and 97% of the vaccinees in the 1/5- and 1/10-dose arms, respectively, were responders, versus 94% in the full-dose arm; for serogroup A, 92% and 88% were responders, respectively, versus 95%. Non-inferiority was demonstrated between the full dose and both fractional doses in SBA seroresponse against serogroups W135 and Y, in total population analysis. Non-inferiority was shown between the full and 1/5 doses for serogroup A in the population non-immune prior to vaccination. Non-inferiority was not shown for any of the fractionate doses for serogroup C. Safety and tolerability data were favourable, as observed in other studies.While the advent of conjugate A vaccine is anticipated to largely contribute to control serogroup A outbreaks in Africa, the scale-up of its production will not cover the entire "Meningitis Belt" target population for at least the next 3 to 5 years. In view of the current shortage of meningococcal vaccines for Africa

Maximizing Tumor Immunity With Fractionated Radiation

Energy Technology Data Exchange (ETDEWEB)

Schaue, Doerthe, E-mail: dschaue@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Ratikan, Josephine A.; Iwamoto, Keisuke S.; McBride, William H. [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States)

2012-07-15

Purpose: Technologic advances have led to increased clinical use of higher-sized fractions of radiation dose and higher total doses. How these modify the pathways involved in tumor cell death, normal tissue response, and signaling to the immune system has been inadequately explored. Here we ask how radiation dose and fraction size affect antitumor immunity, the suppression thereof, and how this might relate to tumor control. Methods and Materials: Mice bearing B16-OVA murine melanoma were treated with up to 15 Gy radiation given in various-size fractions, and tumor growth followed. The tumor-specific immune response in the spleen was assessed by interferon-{gamma} enzyme-linked immunospot (ELISPOT) assay with ovalbumin (OVA) as the surrogate tumor antigen and the contribution of regulatory T cells (Tregs) determined by the proportion of CD4{sup +}CD25{sup hi}Foxp3{sup +} T cells. Results: After single doses, tumor control increased with the size of radiation dose, as did the number of tumor-reactive T cells. This was offset at the highest dose by an increase in Treg representation. Fractionated treatment with medium-size radiation doses of 7.5 Gy/fraction gave the best tumor control and tumor immunity while maintaining low Treg numbers. Conclusions: Radiation can be an immune adjuvant, but the response varies with the size of dose per fraction. The ultimate challenge is to optimally integrate cancer immunotherapy into radiation therapy.

Spatiotemporal Fractionation Schemes for Irradiating Large Cerebral Arteriovenous Malformations

Energy Technology Data Exchange (ETDEWEB)

Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Bussière, Marc R. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Chapman, Paul H. [Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (United States); Loeffler, Jay S.; Shih, Helen A. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2016-07-01

Purpose: To optimally exploit fractionation effects in the context of radiosurgery treatments of large cerebral arteriovenous malformations (AVMs). In current practice, fractionated treatments divide the dose evenly into several fractions, which generally leads to low obliteration rates. In this work, we investigate the potential benefit of delivering distinct dose distributions in different fractions. Methods and Materials: Five patients with large cerebral AVMs were reviewed and replanned for intensity modulated arc therapy delivered with conventional photon beams. Treatment plans allowing for different dose distributions in all fractions were obtained by performing treatment plan optimization based on the cumulative biologically effective dose delivered at the end of treatment. Results: We show that distinct treatment plans can be designed for different fractions, such that high single-fraction doses are delivered to complementary parts of the AVM. All plans create a similar dose bath in the surrounding normal brain and thereby exploit the fractionation effect. This partial hypofractionation in the AVM along with fractionation in normal brain achieves a net improvement of the therapeutic ratio. We show that a biological dose reduction of approximately 10% in the healthy brain can be achieved compared with reference treatment schedules that deliver the same dose distribution in all fractions. Conclusions: Boosting complementary parts of the target volume in different fractions may provide a therapeutic advantage in fractionated radiosurgery treatments of large cerebral AVMs. The strategy allows for a mean dose reduction in normal brain that may be valuable for a patient population with an otherwise normal life expectancy.

Test of equal effect per fraction and estimation of initial clonogen number in microcolony assays of survival after fractionated irradiation

International Nuclear Information System (INIS)

Thames, H.D.; Withers, H.R.

1980-01-01

In the use of multifraction microcolony assays to infer the low-dose response of in situ renewal systems such as intestinal crypts, the assumption of equal effect per dose fraction is required. Moreover, the construction of a cell-survival curve requires knowledge of the initial count of cells capable of repopulating each renewal structure. We describe a method of designing fractionation protocols which provides a regression estimate of the initial number of clonogens per renewal structure and a test of the hypothesis of equal effect per fraction. The essential factor in the experimental design is the use of common dose fractions (use of the same dose per fraction in series with different numbers of fractions). Applications of the method to data for which the assumption of equal effect per fraction holds (four-hour fractionation interval murine testis study) and does not hold (one-hour fractionation interval murine jejunal crypt study) are presented. (author)

Prescription dose and fractionation predict improved survival after stereotactic radiotherapy for brainstem metastases

Directory of Open Access Journals (Sweden)

Leeman Jonathan E

2012-07-01

Full Text Available Abstract Background Brainstem metastases represent an uncommon clinical presentation that is associated with a poor prognosis. Treatment options are limited given the unacceptable risks associated with surgical resection in this location. However, without local control, symptoms including progressive cranial nerve dysfunction are frequently observed. The objective of this study was to determine the outcomes associated with linear accelerator-based stereotactic radiotherapy or radiosurgery (SRT/SRS of brainstem metastases. Methods We retrospectively reviewed 38 tumors in 36 patients treated with SRT/SRS between February 2003 and December 2011. Treatment was delivered with the Cyberknife™ or Trilogy™ radiosurgical systems. The median age of patients was 62 (range: 28–89. Primary pathologies included 14 lung, 7 breast, 4 colon and 11 others. Sixteen patients (44% had received whole brain radiation therapy (WBRT prior to SRT/SRS; ten had received prior SRT/SRS at a different site (28%. The median tumor volume was 0.94 cm3 (range: 0.01-4.2 with a median prescription dose of 17 Gy (range: 12–24 delivered in 1–5 fractions. Results Median follow-up for the cohort was 3.2 months (range: 0.4-20.6. Nineteen patients (52% had an MRI follow-up available for review. Of these, one patient experienced local failure corresponding to an actuarial 6-month local control of 93%. Fifteen of the patients with available follow-up imaging (79% experienced intracranial failure outside of the treatment volume. The median time to distant intracranial failure was 2.1 months. Six of the 15 patients with distant intracranial failure (40% had received previous WBRT. The actuarial overall survival rates at 6- and 12-months were 27% and 8%, respectively. Predictors of survival included Graded Prognostic Assessment (GPA score, greater number of treatment fractions, and higher prescription dose. Three patients experienced acute treatment-related toxicity consisting of

A secretome analysis reveals that PPARα is upregulated by fractionated-dose γ-irradiation in three-dimensional keratinocyte cultures

International Nuclear Information System (INIS)

Lee, Jee Yong; Kim, Hyun Ji; Yi, Jae Youn

2016-01-01

A three-dimensional (3D) environment composed of properly interconnected and differentiated cells that allows communication and cooperation among cells via secreted molecules would be expected to more accurately reflect cellular responses. Here, we investigated γ-irradiation-induced changes in the secretome of 3D-cultured keratinocytes. An analysis of keratinocyte secretome profiles following fractionated-dose γ-irradiation revealed changes in genes involved in cell adhesion, angiogenesis, and the immune system. Notably, peroxisome proliferator-activated receptor-(PPARα) was upregulated in response to fractionated-dose γ-irradiation. This upregulation was associated with an increase in the transcription of known PPARα target genes, including angiopoietin-like protein 4, dermokine and kallikrein-related peptide 12, which were differentially regulated by fractionated-dose γ-irradiation. Collectively, our data imply a mechanism linking γ-irradiation and secretome changes, and suggest that these changes could play a significant role in the coordinated cellular responses to harmful ionizing radiation, such as those associated with radiation therapy. This extension of our understanding of γ-irradiation-induced secretome changes has the potential to improve radiation therapy strategies. Control of inflammatory waves, improved wound healing, and stabilization of the skin barrier are imperative for minimizing such injuries. Therefore, PPARα agonists and antagonists have the potential to become important therapeutic agents for the treatment of γ-irradiation induced skin damage. Specifically, our analysis suggests that the undesirable consequences of long-term exposure to ionizing radiation could be alleviated by PPARα agonists

A secretome analysis reveals that PPARα is upregulated by fractionated-dose γ-irradiation in three-dimensional keratinocyte cultures

Energy Technology Data Exchange (ETDEWEB)

Lee, Jee Yong; Kim, Hyun Ji; Yi, Jae Youn [Korea Institute of Radiation and Medical Sciences, Daejeon (Korea, Republic of)

2016-05-15

A three-dimensional (3D) environment composed of properly interconnected and differentiated cells that allows communication and cooperation among cells via secreted molecules would be expected to more accurately reflect cellular responses. Here, we investigated γ-irradiation-induced changes in the secretome of 3D-cultured keratinocytes. An analysis of keratinocyte secretome profiles following fractionated-dose γ-irradiation revealed changes in genes involved in cell adhesion, angiogenesis, and the immune system. Notably, peroxisome proliferator-activated receptor-(PPARα) was upregulated in response to fractionated-dose γ-irradiation. This upregulation was associated with an increase in the transcription of known PPARα target genes, including angiopoietin-like protein 4, dermokine and kallikrein-related peptide 12, which were differentially regulated by fractionated-dose γ-irradiation. Collectively, our data imply a mechanism linking γ-irradiation and secretome changes, and suggest that these changes could play a significant role in the coordinated cellular responses to harmful ionizing radiation, such as those associated with radiation therapy. This extension of our understanding of γ-irradiation-induced secretome changes has the potential to improve radiation therapy strategies. Control of inflammatory waves, improved wound healing, and stabilization of the skin barrier are imperative for minimizing such injuries. Therefore, PPARα agonists and antagonists have the potential to become important therapeutic agents for the treatment of γ-irradiation induced skin damage. Specifically, our analysis suggests that the undesirable consequences of long-term exposure to ionizing radiation could be alleviated by PPARα agonists.

Comparative evaluation of multiple fractions per day radiotherapy and conventional fractionated radiotherapy in squamous cell carcinoma of esophagus

International Nuclear Information System (INIS)

Andrabi, W.H.; Akhtar, S.; Kharadi, M.Y.; Mushtaq, G.; Zargar, S.A.

1999-01-01

Dose fractionated is important in radiotherapy in order to achieve the desired results. There are regimes which are accepted and followed worldwide. Five fractions per week for a full course of treatment is regarded as standard fractionation regimen. Interest has lately been developed to alter this and try regimes like hyper and accelerated fractionations. In the former, smaller doses per fraction than usual are given in several fractions on each treating day, with no change in overall time. In the latter, conventionally sized fractions are given as two or three per day with a shortening of overall time. As the dose fraction in our case is high, we spilt the full course of treatment introducing a gap of one week between the treatment schedules. The results obtained are fairly good in comparison with conventional radiotherapy regimes. (author)

Experience of micromultileaf collimator linear accelerator based single fraction stereotactic radiosurgery: Tumor dose inhomogeneity, conformity, and dose fall off

Energy Technology Data Exchange (ETDEWEB)

Hong, Linda X.; Garg, Madhur; Lasala, Patrick; Kim, Mimi; Mah, Dennis; Chen, Chin-Cheng; Yaparpalvi, Ravindra; Mynampati, Dinesh; Kuo, Hsiang-Chi; Guha, Chandan; Kalnicki, Shalom [Department of Radiation Oncology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Neurosurgery, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Epidemiology and Population Health, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Radiation Oncology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States)

2011-03-15

Purpose: Sharp dose fall off outside a tumor is essential for high dose single fraction stereotactic radiosurgery (SRS) plans. This study explores the relationship among tumor dose inhomogeneity, conformity, and dose fall off in normal tissues for micromultileaf collimator (mMLC) linear accelerator (LINAC) based cranial SRS plans. Methods: Between January 2007 and July 2009, 65 patients with single cranial lesions were treated with LINAC-based SRS. Among them, tumors had maximum diameters {<=}20 mm: 31; between 20 and 30 mm: 21; and >30 mm: 13. All patients were treated with 6 MV photons on a Trilogy linear accelerator (Varian Medical Systems, Palo Alto, CA) with a tertiary m3 high-resolution mMLC (Brainlab, Feldkirchen, Germany), using either noncoplanar conformal fixed fields or dynamic conformal arcs. The authors also created retrospective study plans with identical beam arrangement as the treated plan but with different tumor dose inhomogeneity by varying the beam margins around the planning target volume (PTV). All retrospective study plans were normalized so that the minimum PTV dose was the prescription dose (PD). Isocenter dose, mean PTV dose, RTOG conformity index (CI), RTOG homogeneity index (HI), dose gradient index R{sub 50}-R{sub 100} (defined as the difference between equivalent sphere radius of 50% isodose volume and prescription isodose volume), and normal tissue volume (as a ratio to PTV volume) receiving 50% prescription dose (NTV{sub 50}) were calculated. Results: HI was inversely related to the beam margins around the PTV. CI had a ''V'' shaped relationship with HI, reaching a minimum when HI was approximately 1.3. Isocenter dose and mean PTV dose (as percentage of PD) increased linearly with HI. R{sub 50}-R{sub 100} and NTV{sub 50} initially declined with HI and then reached a plateau when HI was approximately 1.3. These trends also held when tumors were grouped according to their maximum diameters. The smallest tumor group

Radical radiotherapy for invasive bladder cancer: What dose and fractionation schedule to choose?

International Nuclear Information System (INIS)

Pos, Floris J.; Hart, Guus; Schneider, Christoph; Sminia, Peter

2006-01-01

Purpose: To establish the α/β ratio of bladder cancer from different radiotherapy schedules reported in the literature and provide guidelines for the design of new treatment schemes. Methods and Materials: Ten external beam radiotherapy (EBRT) and five brachytherapy schedules were selected. The biologically effective dose (BED) of each schedule was calculated. Logistic modeling was used to describe the relationship between 3-year local control (LC3y) and BED. Results: The estimated α/β ratio was 13 Gy (95% confidence interval [CI], 2.5-69 Gy) for EBRT and 24 Gy (95% CI, 1.3-460 Gy) for EBRT and brachytherapy combined. There is evidence for an overall dose-response relationship. After an increase in total dose of 10 Gy, the odds of LC3y increase by a factor of 1.44 (95% CI, 1.23-1.70) for EBRT and 1.47 (95% CI, 1.25-1.72) for the data sets of EBRT and brachytherapy combined. Conclusion: With the clinical data currently available, a reliable estimation of the α/β ratio for bladder cancer is not feasible. It seems reasonable to use a conventional α/β ratio of 10-15 Gy. Dose escalation could significantly increase local control. There is no evidence to support short overall treatment times or large fraction sizes in radiotherapy for bladder cancer

Mouse skin damages caused by fractionated irradiation with carbon ions

International Nuclear Information System (INIS)

Ando, K.; Chen, Y.J.; Ohira, C.; Nojima, K.; Ando, S.; Kobayashi, N.; Ohbuchi, T.; Shimizu, W.; Koike, S.; Kanai, T.

1997-01-01

We have investigated carbon-dose responses of early and late skin damages after daily fractionations to the mouse leg. Depilated legs were irradiated with 7 different positions within 290 MeV/u carbon beams. Fractionation schedules were 1, 2, 4 and 8 daily fractions. Skin reaction was scored every other day for 32 days. Five highest scores in individual mice were averaged, and used as averaged peak reaction. The isoeffect doses to produce an averaged peak skin reaction of 3.0 (moist desquamation) on dose-response curves were calculated with 95% confidence limit. The isoeffect dose for control gamma rays constantly increased with an increase in the number of fraction. The isoeffect doses in low LET carbon ions of 14- and 20 keV/μm also increased up to 4 fractions, but did not increase when 4 fractions increased to 8 fractions. The saturation of isoeffect dose was more prominently observed for 40 keV/μm in such that the isoeffect doses did not change among 2, 4 and 8 fractions. The isoeffect doses for LET higher than 50 keV/μm were smaller than those for lower LET. However, the isoeffect doses for 50-, 60-, 80- and 100 keV/μ steadily increased with an increase in the number of fraction and did not show any saturation up to 8 fractions. Relation between LET and RBE was linear for all fractionation schedules. The slope of regression line in 4 fractions was steepest, and significantly (P<0.05) different from that in 1 fraction. (orig.)

Mouse skin damages caused by fractionated irradiation with carbon ions

Energy Technology Data Exchange (ETDEWEB)

Ando, K; Chen, Y J; Ohira, C; Nojima, K; Ando, S; Kobayashi, N; Ohbuchi, T; Shimizu, W [Space and Particle Radiation Science Research Group, Chiba (Japan); Koike, S; Kanai, T [National Inst. of Radiological Sciences, Chiba (Japan). Div. of Accelerator Physics

1997-09-01

We have investigated carbon-dose responses of early and late skin damages after daily fractionations to the mouse leg. Depilated legs were irradiated with 7 different positions within 290 MeV/u carbon beams. Fractionation schedules were 1, 2, 4 and 8 daily fractions. Skin reaction was scored every other day for 32 days. Five highest scores in individual mice were averaged, and used as averaged peak reaction. The isoeffect doses to produce an averaged peak skin reaction of 3.0 (moist desquamation) on dose-response curves were calculated with 95% confidence limit. The isoeffect dose for control gamma rays constantly increased with an increase in the number of fraction. The isoeffect doses in low LET carbon ions of 14- and 20 keV/{mu}m also increased up to 4 fractions, but did not increase when 4 fractions increased to 8 fractions. The saturation of isoeffect dose was more prominently observed for 40 keV/{mu}m in such that the isoeffect doses did not change among 2, 4 and 8 fractions. The isoeffect doses for LET higher than 50 keV/{mu}m were smaller than those for lower LET. However, the isoeffect doses for 50-, 60-, 80- and 100 keV/{mu} steadily increased with an increase in the number of fraction and did not show any saturation up to 8 fractions. Relation between LET and RBE was linear for all fractionation schedules. The slope of regression line in 4 fractions was steepest, and significantly (P<0.05) different from that in 1 fraction. (orig.)

Positron emission tomography for the dose monitoring of intra-fractionally moving targets in ion beam therapy

International Nuclear Information System (INIS)

Stuetzer, Kristin

2014-01-01

Ion beam therapy (IBT) is a promising treatment option in radiotherapy. The characteristic physical and biological properties of light ion beams allow for the delivery of highly tumor conformal dose distributions. Related to the sparing of surrounding healthy tissue and nearby organs at risk, it is feasible to escalate the dose in the tumor volume to reach higher tumor control and survival rates. Remarkable clinical outcome was achieved with IBT for radio-resistant, deep-seated, static and well fixated tumor entities. Presumably, more patients could benefit from the advantages of IBT if it would be available for more frequent tumor sites. Those located in the thorax and upper abdominal region are commonly subjected to intra-fractional, respiration related motion. Different motion-compensated dose delivery techniques have been developed for active field shaping with scanned pencil beams and are at least available under experimental conditions at the GSI Helmholtzzentrum fuer Schwerionenforschung (GSI) in Darmstadt, Germany. Since minor unexpected anatomical changes e.g. related to patient mispositioning, tumour shrinkage or tissue swelling could already lead to remarkable deviations between planned and delivered dose distribution, a valuable dose monitoring system is desired for IBT. So far, positron emission tomography (PET) is the only in vivo, in situ and non-invasive qualitative dose monitoring method applied under clinical conditions. Conclusions about the delivered dose distribution can be drawn indirectly from a comparison between two β + -activity distributions: the measured one and an expected one generated by a Monte-Carlo simulation. Dedicated phantoms mainly made up of polymethyl methacrylate (PMMA) and a motion table for regular one-dimensional (1D) motion patterns have been designed and manufactured for the experiments. Furthermore, the general applicability of the 4D MLEM algorithm for more complex motion patterns has been demonstrated by the

Increasing Fractional Doses Increases the Probability of Benign PSA Bounce in Patients Undergoing Definitive HDR Brachytherapy for Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Hauck, Carlin R.; Ye, Hong; Chen, Peter Y.; Gustafson, Gary S.; Limbacher, Amy; Krauss, Daniel J., E-mail: Daniel.krauss@beaumont.edu

2017-05-01

Purpose: Prostate-specific antigen (PSA) bounce is a temporary elevation of the PSA level above a prior nadir. The purpose of this study was to determine whether the frequency of a PSA bounce following high-dose-rate (HDR) interstitial brachytherapy for the treatment of prostate cancer is associated with individual treatment fraction size. Methods and Materials: Between 1999 and 2014, 554 patients underwent treatment of low- or intermediate-risk prostate cancer with definitive HDR brachytherapy as monotherapy and had ≥3 subsequent PSA measurements. Four different fraction sizes were used: 950 cGy × 4 fractions, 1200 cGy × 2 fractions, 1350 cGy × 2 fractions, 1900 cGy × 1 fraction. Four definitions of PSA bounce were applied: ≥0.2, ≥0.5, ≥1.0, and ≥2.0 ng/mL above the prior nadir with a subsequent return to the nadir. Results: The median follow-up period was 3.7 years. The actuarial 3-year rate of PSA bounce for the entire cohort was 41.3%, 28.4%, 17.4%, and 6.8% for nadir +0.2, +0.5, +1.0, and +2.0 ng/mL, respectively. The 3-year rate of PSA bounce >0.2 ng/mL was 42.2%, 32.1%, 41.0%, and 59.1% for the 950-, 1200-, 1350-, and 1900-cGy/fraction levels, respectively (P=.002). The hazard ratio for bounce >0.2 ng/mL for patients receiving a single fraction of 1900 cGy compared with those receiving treatment in multiple fractions was 1.786 (P=.024). For patients treated with a single 1900-cGy fraction, the 1-, 2-, and 3-year rates of PSA bounce exceeding the Phoenix biochemical failure definition (nadir +2 ng/mL) were 4.5%, 18.7%, and 18.7%, respectively, higher than the rates for all other administered dose levels (P=.025). Conclusions: The incidence of PSA bounce increases with single-fraction HDR treatment. Knowledge of posttreatment PSA kinetics may aid in decision making regarding management of potential biochemical failures.

Increasing Fractional Doses Increases the Probability of Benign PSA Bounce in Patients Undergoing Definitive HDR Brachytherapy for Prostate Cancer

International Nuclear Information System (INIS)

Hauck, Carlin R.; Ye, Hong; Chen, Peter Y.; Gustafson, Gary S.; Limbacher, Amy; Krauss, Daniel J.

2017-01-01

Purpose: Prostate-specific antigen (PSA) bounce is a temporary elevation of the PSA level above a prior nadir. The purpose of this study was to determine whether the frequency of a PSA bounce following high-dose-rate (HDR) interstitial brachytherapy for the treatment of prostate cancer is associated with individual treatment fraction size. Methods and Materials: Between 1999 and 2014, 554 patients underwent treatment of low- or intermediate-risk prostate cancer with definitive HDR brachytherapy as monotherapy and had ≥3 subsequent PSA measurements. Four different fraction sizes were used: 950 cGy × 4 fractions, 1200 cGy × 2 fractions, 1350 cGy × 2 fractions, 1900 cGy × 1 fraction. Four definitions of PSA bounce were applied: ≥0.2, ≥0.5, ≥1.0, and ≥2.0 ng/mL above the prior nadir with a subsequent return to the nadir. Results: The median follow-up period was 3.7 years. The actuarial 3-year rate of PSA bounce for the entire cohort was 41.3%, 28.4%, 17.4%, and 6.8% for nadir +0.2, +0.5, +1.0, and +2.0 ng/mL, respectively. The 3-year rate of PSA bounce >0.2 ng/mL was 42.2%, 32.1%, 41.0%, and 59.1% for the 950-, 1200-, 1350-, and 1900-cGy/fraction levels, respectively (P=.002). The hazard ratio for bounce >0.2 ng/mL for patients receiving a single fraction of 1900 cGy compared with those receiving treatment in multiple fractions was 1.786 (P=.024). For patients treated with a single 1900-cGy fraction, the 1-, 2-, and 3-year rates of PSA bounce exceeding the Phoenix biochemical failure definition (nadir +2 ng/mL) were 4.5%, 18.7%, and 18.7%, respectively, higher than the rates for all other administered dose levels (P=.025). Conclusions: The incidence of PSA bounce increases with single-fraction HDR treatment. Knowledge of posttreatment PSA kinetics may aid in decision making regarding management of potential biochemical failures.

Optimal timing and frequency of bone marrow soup therapy for functional restoration of salivary glands injured by single-dose or fractionated irradiation.

Science.gov (United States)

Fang, Dongdong; Shang, Sixia; Liu, Younan; Bakkar, Mohammed; Sumita, Yoshinori; Seuntjens, Jan; Tran, Simon D

2018-02-01

Injections of bone marrow (BM) cell extract, known as 'BM soup', were previously reported to mitigate ionizing radiation (IR) injury to salivary glands (SGs). However, the optimal starting time and frequency to maintain BM soup therapeutic efficacy remains unknown. This study tested the optimal starting time and frequency of BM soup injections in mice radiated with either a single dose or a fractionated dose. First, BM soup treatment was started at 1, 3 or 7 weeks post-IR; positive (non-IR) and negative (IR) control mice received injections of saline (vehicle control). Second, BM soup-treated mice received injections at different frequencies (1, 2, 3 and 5 weekly injections). Third, a 'fractionated-dose radiation' model to injure mouse SGs was developed (5 Gy × 5 days) and compared with the single high dose radiation model. All mice (n = 65) were followed for 16 weeks post-IR. The results showed that starting injections of BM soup between 1 and 3 weeks mitigated the effect of IR-induced injury to SGs and improved the restoration of salivary function. Although the therapeutic effect of BM soup lessens after 8 weeks, it can be sustained by increasing the frequency of weekly injections. Moreover, both single-dose and fractionated-dose radiation models are efficient and comparable in inducing SG injury and BM soup treatments are effective in restoring salivary function in both radiation models. In conclusion, starting injections of BM soup within 3 weeks post-radiation, with 5 weekly injections, maintains 90-100% of saliva flow in radiated mice. Copyright © 2017 John Wiley & Sons, Ltd.

Low-dose fractionated percutaneous teletherapy in age-related macular degeneration with subfoveolar neovascularization - 3 year results

International Nuclear Information System (INIS)

Schittkowski, M.; Schneider, H.; Guthoff, R.; Grueschow, K.; Ziegler, P.G.; Fietkau, R.

2001-01-01

The effect of low dose fractionated percutaneous teletherapy to visual acuity and the changes in subfoveolar neovascular membranes in age-related macular degeneration were investigated. Patients and Method: 126 eyes of 118 patients (age 55-89 years; mean 74 ys.) were treated. Best distal and near visual acuity was assessed prior to (= initial visual acuity [IVA]) and 3, 6, 12, 18, 24, and 36 months after teletherapy. Fluorescein angiography was performed prior to and 6, 12, 24 and 36 months after radiation therapy. For analysis patients were divided into different groups by IVA and membrane size. Maximal duration of observation was 36 months. Teletherapy was done by a 9-MeV photon linear accelerator through a lateral port in half-beam technique with a single dose of 2 Gy up to a total dose of 20 Gy within 12 days. Results: No severe negative side effects have been observed. Eight patients reported of epiphora and four patients complained of transient sicca syndrome. Visual acuity decreased more than one line in the group IVA 0.05-0.2. The group IVA 0.3-0.5 remained unchanged for 1 year. We found a tendency for increased visual acuity in group IVA ≥ 0.6 for 18 months. After that time both groups showed decreased visual acuity, but all these patients reported of reduced metamorphopsia and increased color and contrast perception. Conclusions: There is an influence of low dose fractionated percutaneous teletherapy on visual acuity, subfoveal neovascular membranes and metamorphopsia. IVA and duration of anamnesis play an important role. There seems to be no persistent effect; possibly increased dosage will bring a benefit. (orig.) [de

The relative biological effectiveness of fractionated doses of fast neutrons (42 MeV sub d yields Be ) for normal tissues. Pt. 3; Effects on lung function

Energy Technology Data Exchange (ETDEWEB)

Rezvani, M.; Hopewell, J.W.; Robbins, M.E.C.; Hamlet, R. (Churchill Hospital, Oxford (UK)); Barnes, D.W.H.; Sansom, J.M.; Adams, P.J.V. (Medical Research Council, Harwell (UK). Radiobiological Research Unit)

1990-11-01

The effect of single and fractionated doses of fast neutrons (42 MeV{sub d{yields}Bc}) on the early and late radiation responses of the pig lung have been assessed by the measurement of changes in lung function using a {sup 133}Xe washout technique. The results obtained for irradiation schedules with fast neutrons have been compared with those after photon irradiation. There was no statistically significant difference between the values for the relative biological effectiveness (RBE) for the early and late radiation response of the lung. The RBE of the neutron beam increased with decreasing size of dose/fraction with an upper limit value of 4.39 {plus minus} 0.94 for infinitely small X-ray doses per fraction. (author).

Phase I/II trial of single-fraction high-dose-rate brachytherapy-boosted hypofractionated intensity-modulated radiation therapy for localized adenocarcinoma of the prostate.

Science.gov (United States)

Myers, Michael A; Hagan, Michael P; Todor, Dorin; Gilbert, Lynn; Mukhopadhyay, Nitai; Randolf, Jessica; Heimiller, Jeffrey; Anscher, Mitchell S

2012-01-01

A Phase I/II protocol was conducted to examine the toxicity and efficacy of the combination of intensity-modulated radiation therapy (IMRT) with a single-fraction high-dose-rate (HDR) brachytherapy implant. From 2001 through 2006, 26 consecutive patients were treated on the trial. The primary objective was to demonstrate a high rate of completion without experiencing a treatment-limiting toxicity. Eligibility was limited to patients with T stage ≤2b, prostate-specific antigen (PSA) ≤20, and Gleason score ≤7. Treatment began with a single HDR fraction of 6Gy to the entire prostate and 9Gy to the peripheral zone, followed by IMRT optimized to deliver in 28 fractions with a normalized total dose of 70Gy. Patients received 50.4Gy to the pelvic lymph node. The prostate dose (IMRT and HDR) resulted in an average biologic equivalent dose >128Gy (α/β=3). Patients whose pretreatment PSA was ≥10ng/mL, Gleason score 7, or stage ≥T2b received short-term androgen ablation. Median followup was 53 months (9-68 months). There were no biochemical failures by either the American Society of Therapeutic Radiology and Oncology or the Phoenix definitions. The median nadir PSA was 0.32ng/mL. All the 26 patients completed the treatment as prescribed. The rate of Grade 3 late genitourinary toxicity was 3.8% consisting of a urethral stricture. There was no other Grade 3 or 4 genitourinary or gastrointestinal toxicities. Single-fraction HDR-boosted IMRT is a safe effective method of dose escalation for localized prostate cancer. Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Evaluation of the efficacy of palliative irradiation with high fractionated doses and planned intervals of patients with advanced cancer of the oral cavity and pharynx

International Nuclear Information System (INIS)

Skolyszewski, J.; Reinfuss, M.

1988-01-01

200 patients, previously not treated, with advanced highly differentiated cancer of the oral cavity and pharynx have been palliatively irradiated in the Oncology Center in Cracow in the years 1976-1985. Megavoltage irradiation with fractionated doses 4-5 Gy up to the dose of 20 Gy to the tumor with 4-5 fractions during 4-7 days has been applied. 64 patients received 20 Gy as simple dose, in 65 cases such dose has been repeated after month. 71 patients have been irradiated for the third time with similar dose after another 1 month interval. Partial regression of 25-50% of the tumor volume has been obtained after the first series of irradiation in 19% of patients and more than 50% in 28% of patients, complete regression in 4% of patients. 15,5% of the total number of patients survived 1 year since the initiation of the irradiation, 5% without symptoms of the neoplasm. Worse prognosis is connected with major advancement of the tumor (T 4 , N 2 ), poor general condition, cachexia and alcohol addition. Absence of improvement after the first series of irradiations indicates the non-effectiveness of the treatment. Palliative treatment by irradiation with high fractionated doses and planned interval is a safe and efficacious method. 1 fig., 6 tabs., 14 refs. (author)

Stage, tumor growth rate and optimal dose fractionation schedules in the treatment of squamous cell carcinoma of the head and neck

International Nuclear Information System (INIS)

Sugawara, Tadashi; Morita, Mamoru; Aihara, Toshinori; Tanaka, Osamu

1983-01-01

In 77 patients with cancer of the head and neck, 45 patients received radiotherapy alone, while 32 patients with T 1 or T 2 glottic cancer received combined therapy with laryngomicrosurgery performed prior to or during the course of irradiation. These T 1 and T 2 groups were separately analyzed from other T 1 and T 2 groups as T sub(LMS). Local recurrence rates were compared concerning overall time and fraction size in following three subgroups, i.e., T sub(LMS), Tsub(1+2), and Tsub(3+4). No significant correlation was detected between total dose converted to partial tolerance (PT) and local control in all subgroups except for Tsub(3+4), in which local recurrence rate was rather higher in high PT range. Local control was significantly dependent on overall treatment time and fraction size, differently by tumor stage. Favorable fractionation schedules considered as optimal for T sub(LMS) were those in which treatment was given 5 times weekly with a daily dose rate more than 196 rad in a shorter overall time of less than 42 days. In contrast to T sub(LMS), effective schedules for Tsub(3+4) consisted of longer overall time of more than 60 days and a lower daily dose rate of less than 153 rad. In Tsub(1+2), the optimal schedule was needed to be altered according to rapidness of progression of disease characterised by duration of the complaints, which was statistically proved to be significantly shorter in Tsub(1+2) than Tsub(3+4). Rapidity-adjusted schedule consisted of a shorter over-all time of less than 49 days with a daily dose rate of more than 175 rad 5 fractions a week for a case having a duration of complaints of less than 2.9 months, and a longer overall time of more than 50 days with a daily dose rate of less than 174 rad for a case having a duration of more than 3 months. (J.P.N.)

Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases

International Nuclear Information System (INIS)

Nielsen, O.S.; Bentzen, S.M.; Sandberg, E.; Gadeberg, C.C.; Timothy, A.R.

1998-01-01

Purpose: Data in the literature suggest that for painful bone metastases a single dose is as effective as fractionated radiotherapy. In the present multicentre prospective trial, the effects of 8 Gy x1 and 5 Gy x4 were compared. Patients and methods: A total of 241 patients were randomized to 8 Gy (122 patients) or 20 Gy (119 patients). The primary tumour was in the breast in 39% of patients, in the prostate in 34% of patients, in the lung in 13% of patients and in other locations in 14% of patients. Outcome measures were pain relief as measured by VAS and in half of the patients also by a five-point categorical pain scale, global quality of life (QoL) and analgesic consumption. Evaluation was performed before and 4, 8, 12 and 20 weeks after treatment. Results: A total of 239 patients were evaluable for response. The two groups did not differ with respect to age, sex, primary tumour, metastasis localization, analgesic consumption (type and dose), performance status, prior systemic treatment, degree of pain and QoL. The treatment was completed as planned in 98% of patients. The degree of pain relief did not differ between the two treatment groups. At 4 weeks the difference in pain relief was 6% (95% CI 7, 20%) and at 8 weeks the difference was 13% (95% CI 3, 28%). Neither was there any significant difference in the duration of pain relief, the number of new painful sites and the need for reirradiation and toxicity was minor. Conclusion: The present randomized study showed that a single fraction of 8 Gy was as effective as 5 Gy x4 in relieving pain from bone metastasis. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

Dose mapping sensitivity to deformable registration uncertainties in fractionated radiotherapy – applied to prostate proton treatments

International Nuclear Information System (INIS)

Tilly, David; Tilly, Nina; Ahnesjö, Anders

2013-01-01

Calculation of accumulated dose in fractionated radiotherapy based on spatial mapping of the dose points generally requires deformable image registration (DIR). The accuracy of the accumulated dose thus depends heavily on the DIR quality. This motivates investigations of how the registration uncertainty influences dose planning objectives and treatment outcome predictions. A framework was developed where the dose mapping can be associated with a variable known uncertainty to simulate the DIR uncertainties in a clinical workflow. The framework enabled us to study the dependence of dose planning metrics, and the predicted treatment outcome, on the DIR uncertainty. The additional planning margin needed to compensate for the dose mapping uncertainties can also be determined. We applied the simulation framework to a hypofractionated proton treatment of the prostate using two different scanning beam spot sizes to also study the dose mapping sensitivity to penumbra widths. The planning parameter most sensitive to the DIR uncertainty was found to be the target D 95 . We found that the registration mean absolute error needs to be ≤0.20 cm to obtain an uncertainty better than 3% of the calculated D 95 for intermediate sized penumbras. Use of larger margins in constructing PTV from CTV relaxed the registration uncertainty requirements to the cost of increased dose burdens to the surrounding organs at risk. The DIR uncertainty requirements should be considered in an adaptive radiotherapy workflow since this uncertainty can have significant impact on the accumulated dose. The simulation framework enabled quantification of the accuracy requirement for DIR algorithms to provide satisfactory clinical accuracy in the accumulated dose

Influence of Exposure to Fractionated Dose of Gamma Radiation and Antioxidants Supplementation to Mice on program cell death induction

International Nuclear Information System (INIS)

Hanafi, A.

2010-01-01

The previous studies reported that the tumor suppressor protein (P53) is not functioning correctly in most human cancers, and that it plays a crucial role in the prevention of tumor development. This study was designed to evaluate if exposure to fractionated dose of gamma radiation impair function of P53 by the administration of antioxidants. Group of control mice was used. Another groups treated with 3 mg/mouse/day of Antox drug which contains the three main antioxidant vitamins (A, C, and E) together with trace element selenium for 15 days. Another group subjected to 1 Gy of gamma radiation 5 times every other day either alone or combined with the Antox drug supplementation. Hepatic and renal functions were evaluated. Antioxidant markers (MDA and GSH) levels, histopathological changes and P53 expression were recorded in liver and kidney tissues. Animals treated with Antox showed some increase in liver transaminases, non significant changes in total protein and albumin levels, a non significant change in kidney function profiles, a non significant increase in MDA and a significant increase in GSH levels in liver and kidney tissues. However, the exposure of mice to fractionated dose of gamma radiation led to a significant increase in kidney function profiles, AST and ALT activity, a significant decrease in total protein and albumin level, a significant increase in MDA levels and a significant decrease in GSH levels in liver and kidney were observed. Exposure of experimental animals post treatment with Antox drug to fractionated dose of gamma radiation revealed a significant amelioration in liver and kidney function profiles, a highly significant decrease in MDA levels and a significant increase in GSH level in comparison with irradiated group. Histopathological changes in liver and kidney recorded the same alterations observed with the biochemical parameters. P53 expression negatively expressed in normal liver and kidney tissues. However, the exposure of mice to

Autologous stem cell transplantation following high-dose whole-body irradiation of dogs - influence of cell number and fractionation regimes

International Nuclear Information System (INIS)

Bodenberger, U.

1981-01-01

The acute radiation syndrome after a single dose of 1600 R (approx. 12-14 Gy in body midline) and after fractionated irradiation with 2400 R (approx. 18-20 Gy) was studied with regard to fractionation time and to the number of bone marrow cells infused. The acute radiation syndrome consisted of damage to the alimentary tract and of damage to the hemopoietic system. Damage of hemopoiesis was reversible in dogs which had been given a sufficient amount of hemopoietic cells. Furthermore changes in skin and in the mucous membranes occurred. Hemopoietic recovery following infusion of various amounts of bone marrow was investigated in dogs which were irradiated with 2400 R within 7 days. Repopulation of bone marrow as well as rise of leukocyte and platelet counts in the peripheral blood was taken as evidence of complete hemopoietic reconstitution. The results indicate that the acute radiation syndrom following 2400 R TBI and autologous BMT can be controlled by fractionation of this dose within 5 or 7 days. The acute gastrointestinal syndrome is aggravated by infusion of a lesser amount of hemopoietic cells. However, TBI with 2400 R does not require greater numbers of hemopoietic cells for restoration of hemopoiesis. Thus, the hemopoiesis supporting tissue can not be damage by this radiation dose to an essential degree. Longterm observations have not revealed serious late defects which could represent a contraindication to the treatment of malignent diseases with 2400 R of TBI. (orig./MG) [de

Effect of Fractionated Low Doses of Gamma Radiation on Some Haematological and Immunological Parameters in Albino Rat

International Nuclear Information System (INIS)

Bahgat, M.M.; Abdel-Khalek, L.G.

2003-01-01

This study was performed on 30 mature male albino rats to evaluate the direct effect of fractionated low doses (0.5 Gy twice weekly) gamma radiation and delayed effect (one month post-irradiation) on some haematological and immunological parameters. The rats were divided into three equal groups, Control and two whole body gamma-irradiated groups the irradiated groups were subjected to total doses of 4 and 8 Grays over a period of one and two months, respectively. The blood samples and peritoneal macrophages were taken twice from each irradiated rats at the end of their irradiation period and after one month post irradiation. Activated peritoneal macrophages in all groups showed significant decrease as compared to control group denoting that irradiation may cause receptor alteration and/or decrease in the phagocytic power of macrophages lasting for a longer time. Throughout the whole experiment there was wide variation in platelet count with no significant or minimal changes in other blood elements. Moreover, in the post irradiation group after two months irradiation, all the haematological parameters tested, except the Hct, were increased as compared to the control group. These results pointed to that the bone marrow and lymphoid organs of the animals can tolerate fractionated low dose irradiation through rapid recovery and/or compensatory stimulation. The presence of many target cells in the post irradiated group increases the red blood cell fragility

SU-F-T-02: Estimation of Radiobiological Doses (BED and EQD2) of Single Fraction Electronic Brachytherapy That Equivalent to I-125 Eye Plaque: By Using Linear-Quadratic and Universal Survival Curve Models

International Nuclear Information System (INIS)

Kim, Y; Waldron, T; Pennington, E

2016-01-01

Purpose: To test the radiobiological impact of hypofractionated choroidal melanoma brachytherapy, we calculated single fraction equivalent doses (SFED) of the tumor that equivalent to 85 Gy of I125-BT for 20 patients. Corresponding organs-at-risks (OARs) doses were estimated. Methods: Twenty patients treated with I125-BT were retrospectively examined. The tumor SFED values were calculated from tumor BED using a conventional linear-quadratic (L-Q) model and an universal survival curve (USC). The opposite retina (α/β = 2.58), macula (2.58), optic disc (1.75), and lens (1.2) were examined. The % doses of OARs over tumor doses were assumed to be the same as for a single fraction delivery. The OAR SFED values were converted into BED and equivalent dose in 2 Gy fraction (EQD2) by using both L-Q and USC models, then compared to I125-BT. Results: The USC-based BED and EQD2 doses of the macula, optic disc, and the lens were on average 118 ± 46% (p 14 Gy). Conclusion: The estimated single fraction doses were feasible to be delivered within 1 hour using a high dose rate source such as electronic brachytherapy (eBT). However, the estimated OAR doses using eBT were 112 ∼ 118% higher than when using the I125-BT technique. Continued exploration of alternative dose rate or fractionation schedules should be followed.

WHO position on the use of fractional doses - June 2017, addendum to vaccines and vaccination against yellow fever WHO: Position paper - June 2013.

Science.gov (United States)

World Health Organization

2017-10-13

This article presents the World Health Organization's (WHO) recommendations on the use of fractional doses of yellow fever vaccines excerpted from the "Yellow fever vaccine: WHO position on the use of fractional doses - June 2017, Addendum to Vaccines and vaccination against yellow fever WHO: Position Paper - June 2013″, published in the Weekly Epidemiological Record [1,2]. This addendum to the 2013 position paper pertains specifically to use of fractional dose YF (fYF) vaccination (fractional dose yellow fever vaccination refers to administration of a reduced volume of vaccine dose, which has been reconstituted as usual per manufacturer recommendations) in the context of YF vaccine supply shortages beyond the capacity of the global stockpile. The current WHO position on the use of yellow fever (YF) vaccine is set out in the 2013 WHO position paper on vaccines and vaccination against YF and those recommendations are unchanged. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of Yellow Fever vaccines were discussed by SAGE in October 2016; evidence presented at these meetings can be accessed at: www.who.int/immunization/sage/meetings/2016/October/presentations_background_docs/en/. Copyright © 2017. Published by Elsevier Ltd.

Extracranial doses during stereotactic radiosurgery and fractionated stereotactic radiotherapy measured with thermoluminescent dosimeter in vivo

Energy Technology Data Exchange (ETDEWEB)

Kim, I.H.; Lim, D.H.; Kim, S.; Hong, S.; Kim, B.K.; Kang, W-S.; Wu, H.G.; Ha, S.W.; Park, C.I. [Seoul National University College of Medicine, Department of Therapeutic Radiology (Korea)

2000-05-01

Recently the usage of 3-dimensional non-coplanar radiotherapy technique is increasing. We measured the extracranial dose and its distribution g the above medical procedures to estimate effect of exit doses of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) of the intracranial target lesions using a linac system developed in our hospital. Among over hundred patients who were treated with SRS or FSRT from 1995 to 1998, radiation dosimetry data of 15 cases with SRS and 20 cases with FSRT were analyzed. All patients were adults. Of SRS cases, 11 were male and 4 were female. Vascular malformation cases were 9, benign tumors were 3, and malignant tumors were 3. Of FSRT cases, males were 12 and females were 8. Primary malignant brain tumors were 5, benign tumors were 6, and metastatic brain tumors were 10. Doses were measured with lithium fluoride TLD chips (7.5% Li-6 and 92.5% Li-7; TLD-100, Harshaw/Filtrol, USA). The chips were attached patient's skin at the various extracranial locations during SRS or FSRT. For SRS, 14-25 Gy were delivered with 1-2 isocenters using 12-38 mm circular tertiary collimators with reference to 50-80% isodose line conforming at the periphery of the target lesions. For FSRT, 5-28 fractions were used to deliver 9-56 Gy to periphery with dose maximum of 10-66 Gy. Both procedures used 6 MV X-ray generated from Clinac-18 (Varian, USA). For SRS procedures, extracranial surface doses (relative doses) were 8.07{+-}4.27 Gy (0.31{+-}0.16% Mean{+-}S.D.) at the upper eyelids, 6.13{+-}4.32 Gy (0.24{+-}0.16%) at the submental jaw, 7.80{+-}5.44 Gy (0.33{+-}0.26%) at thyroid, 1.78{+-}0.64 Gy (0.07{+-}0.02%) at breast, 0.75{+-}0.38 Gy (0.03{+-}0.02%) at umbilicus, 0.40{+-}0.07 Gy (0.02{+-}0.01%) at perineum, and 0.46{+-}0.39 Gy (0.02{+-}0.01%) at scrotum. Thus the farther the distance from the brain, the less the dose to the location. In overall the doses were less than 0.3% and thus less detrimental. For FSRT procedures

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

International Nuclear Information System (INIS)

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

1997-01-01

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

Intervals between multiple fractions per day

International Nuclear Information System (INIS)

Fowler, J.F.

1988-01-01

Assuming the linear quadratic model for dose-response curves enables the proportion of repairable damage to be calculated for any size of dose per fraction. It is given by the beta (dose squared) term, and represents a larger proportion of the total damage for larger doses per fraction, but also for late-reacting than for early-reacting tissues. For example at 2 Gy per fraction, repairable damage could represent nearly half the total damage in late-reacting tissues but only one fifth in early-reacting tissues. Even if repair occurs at the same rate in both tissues, it will obviously take longer for 50% of the damage to fade to an undetectable level (3 or 5%) than for 20% to do so. This means that late reactions require longer intervals than early reactions when multiple fraction per day radiotherapy is planned, even if the half-lives of repair are not different. (orig.)

Clinical results of definitive-dose (50 Gy/25 fractions) preoperative chemoradiotherapy for unresectable esophageal cancer

International Nuclear Information System (INIS)

Ishikawa, Kazuki; Nakamatsu, Kiyoshi; Shiraishi, Osamu; Yasuda, Takushi; Nishimura, Yasumasa

2015-01-01

The clinical results of definitive-dose preoperative chemoradiotherapy (CRT) of 50 Gy/25 fractions/5 weeks for unresectable esophageal cancer were analyzed. Inclusion criteria were unresectable esophageal squamous cell carcinoma with T4b or mediastinal lymph nodes invading to the trachea or aorta. Radiation therapy of 50 Gy/25 fractions/5 weeks was combined concurrently with two courses of FP therapy (CDDP 70 mg/m 2 + 5-FU 700 mg/m 2 /d x 5 days: day 1-5, day 29-33). Tumor response was evaluated 4 weeks after completion of RT. Subtotal esophagectomy was planned 6-8 weeks after RT. Thirty patients (26 male and 4 female) aged from 50-78 years (median 66) were enrolled between 2008 and 2011. The clinical stages according to the 7th edition of UICC were stages II/III/IV, 1/23/6; T1/2/3/4, 1/1/4/24; and N0/1/2/3, 3/25/1/1. All 30 patients completed RT of 50 Gy/ 25 fractions. Initial tumor responses were 21 patients with resectable disease, 7 with unresectable disease, and 2 with progressive disease. Subtotal esophagectomy was performed in 18 (60%) of the 30 patients. Pathological complete response was obtained in five (28%) patients. There were two patients with hospitalization death after surgery (11%). Six of the 7 patients who still had unresectable disease were treated with 1-3 courses of docetaxel, CDDP and 5-FU. Three patients treated without surgery showed long-term survival. The 3-year locoregional control rate and the 3-year overall survival rate for the 30 patients were 70 and 49%, respectively. Definitive-dose preoperative CRT was feasible, and is a promising treatment strategy for unresectable esophageal cancer. (author)

Time-dose modifications

International Nuclear Information System (INIS)

Kian Ang, K.

1987-01-01

Changes in fractionation schedule can be made by various approaches. However, from the first principle, it is anticipated that strategies of hyperfractionation and/or accelerated fractionation offer the most promised in improving the therapeutic ratio. Hyperfractionation is defined as a treatment schedule in which a large number of significantly reduced dose fractions (--1.2 Gy/fraction) is used to give a greater total dose in a conventional overall time period. The results of the pilot studies testing the efficacy of hyperfractionation have been encouraging. The most valid clinical trial of pure hyperfractionation, however, is that conducted by the EORTC. This study compared 70 Gy in 35 fractions or 80.5 Gy in 70 fractions over 7 weeks in the treatment of patients with oropharyngeal carcinomas. The local tumor control was significantly improved in the hyperfractionated arm without increasing the morbidity. Accelerated fractionation is defined as a schedule in which the overall time of treatment is reduced without significant changes in the total dose and fraction size. The strategy has been used to treat patients with malignant gliomas, melanomas and Head and Neck cancers. The data in Head and Neck Cancers seem to be promising

SU-D-BRB-06: Treating Glioblastoma Multiforme (GBM) as a Chronic Disease: Implication of Temporal-Spatial Dose Fractionation Optimization Including Cancer Stem Cell Dynamics

Energy Technology Data Exchange (ETDEWEB)

Yu, V; Nguyen, D; Pajonk, F; Kaprealian, T; Kupelian, P; Steinberg, M; Low, D; Sheng, K [Department of Radiation Oncology, UCLA, Los Angeles, CA (United States)

2015-06-15

Purpose: To explore the feasibility of improving GBM treatment outcome with temporal-spatial dose optimization of an ordinary differential equation (ODE) that models the differentiation and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC). Methods: The ODE was formulated into a non-convex optimization problem with the objective to minimize remaining total cancer cells 500 days from the onset of radiotherapy when the total cancer cell number was 3.5×10{sup 7}, while maintaining normal tissue biological effective dose (BED) of 100Gy resulted from standard prescription of 2Gyx30. Assuming spatially separated CSC and DCC, optimization was also performed to explore the potential benefit from dose-painting the two compartments. Dose escalation to a sub-cell-population in the GTV was also examined assuming that a 2 cm margin around the GTV allows sufficient dose drop-off to 100Gy BED. The recurrence time was determined as the time at which the total cancer cell number regrows to 10{sup 9} cells. Results: The recurrence time with variable fractional doses administered once per week, bi-week and month for one year were found to be 615, 593 and 570 days, superior to the standard-prescription recurrence time of 418 days. The optimal dose-fraction size progression for both uniform and dose-painting to the tumor is low and relatively constant in the beginning and gradually increases to more aggressive fractions at end of the treatment course. Dose escalation to BED of 200Gy to the whole tumor alongside with protracted weekly treatment was found to further delay recurrence to 733 days. Dose-painting of 200 and 500Gy BED to CSC on a year-long weekly schedule further extended recurrence to 736 and 1076 days, respectively. Conclusion: GBM treatment outcome can possibly be improved with a chronic treatment approach. Further dose escalation to the entire tumor or CSC targeted killing is needed to achieve total tumor control. This work

What next in fractionated radiotherapy

International Nuclear Information System (INIS)

Fowler, J.F.

1984-01-01

Trends in models for predicting the total dose required to produce tolerable normal-tissue injury can be seen by the progression from the ''cube root law'', through Strandqvist's slope of 0.22, to NSD, TDF and CRE which have separate time and fraction number exponents, to even better approximations now available. The dose-response formulae that can be used to define the effect of fraction size (and number) include (1) the linear quadratic (LQ) model (2) the two-component (TC) multi-target model and (3) repair-misrepair models. The LQ model offers considerable convenience, requires only two parameters to be determined, and emphasizes the difference between late and early normal-tissue dependence on dose per fraction first shown by exponents greater than the NSD slope of 0.24. Exponents of overall time, e.g. Tsup(0.11), yield the wrong shape of time curve, suggesting that most proliferating occurs early, although it really occurs after a delay depending on the turnover time of the tissue. Improved clinical results are being sought by hyperfractionation, accelerated fractionation, or continuous low dose rate irradiation as in interstitial implants. (U.K.)

Preliminary Results of a Phase 1 Dose-Escalation Trial for Early-Stage Breast Cancer Using 5-Fraction Stereotactic Body Radiation Therapy for Partial-Breast Irradiation

International Nuclear Information System (INIS)

Rahimi, Asal; Thomas, Kimberly; Spangler, Ann; Rao, Roshni; Leitch, Marilyn; Wooldridge, Rachel; Rivers, Aeisha; Seiler, Stephen; Albuquerque, Kevin; Stevenson, Stella; Goudreau, Sally; Garwood, Dan; Haley, Barbara; Euhus, David; Heinzerling, John; Ding, Chuxiong; Gao, Ang; Ahn, Chul; Timmerman, Robert

2017-01-01

Purpose: To evaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose. Methods and Materials: Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size <3 cm. Patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Starting dose was 30 Gy in 5 fractions and was escalated by 2.5 Gy total for each cohort to 40 Gy. Results: In all, 75 patients were enrolled, with a median age of 62 years. Median follow-up for 5 cohorts was 49.9, 42.5, 25.7, 20.3, and 13.5 months, respectively. Only 3 grade 3 toxicities were experienced. There was 1 dose-limiting toxicity in the overall cohort. Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 95.9%, 100%, 96.7%, and 100% at baseline and 6, 12, and 24 months after S-PBI, whereas patients scored the same periods as 86.5%, 97.1%, 95.1%, and 95.3%, respectively. The disagreement rates between MDs and patients during those periods were 9.4%, 2.9%, 1.6%, and 4.7%, respectively. There have been no recurrences or distant metastases. Conclusion: Dose was escalated to the target dose of 40 Gy in 5 fractions, with the occurrence of only 1 dose-limiting toxicity. Patients felt cosmetic results improved within the first year after surgery and stereotactic body radiation therapy. Our results show minimal toxicity with excellent cosmesis; however, further follow-up is warranted in future studies. This study is the first to show the safety, tolerability, feasibility, and cosmesis results of a 5-fraction dose-escalated S-PBI treatment for

Preliminary Results of a Phase 1 Dose-Escalation Trial for Early-Stage Breast Cancer Using 5-Fraction Stereotactic Body Radiation Therapy for Partial-Breast Irradiation

Energy Technology Data Exchange (ETDEWEB)

Rahimi, Asal, E-mail: asal.rahimi@utsouthwestern.edu [University of Texas Southwestern Medical Center, Dallas, Texas (United States); Thomas, Kimberly; Spangler, Ann [University of Texas Southwestern Medical Center, Dallas, Texas (United States); Rao, Roshni; Leitch, Marilyn; Wooldridge, Rachel; Rivers, Aeisha [Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Seiler, Stephen [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Albuquerque, Kevin; Stevenson, Stella [University of Texas Southwestern Medical Center, Dallas, Texas (United States); Goudreau, Sally [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Garwood, Dan [University of Texas Southwestern Medical Center, Dallas, Texas (United States); Haley, Barbara [Department of Medical Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Euhus, David [Department of Surgery, Johns Hopkins University, Baltimore, Maryland (United States); Heinzerling, John [Department of Radiation Oncology, Levine Cancer Institute, Charlotte, North Carolina (United States); Ding, Chuxiong [University of Texas Southwestern Medical Center, Dallas, Texas (United States); Gao, Ang; Ahn, Chul [Department of Statistics, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Timmerman, Robert [University of Texas Southwestern Medical Center, Dallas, Texas (United States)

2017-05-01

Purpose: To evaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose. Methods and Materials: Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size <3 cm. Patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Starting dose was 30 Gy in 5 fractions and was escalated by 2.5 Gy total for each cohort to 40 Gy. Results: In all, 75 patients were enrolled, with a median age of 62 years. Median follow-up for 5 cohorts was 49.9, 42.5, 25.7, 20.3, and 13.5 months, respectively. Only 3 grade 3 toxicities were experienced. There was 1 dose-limiting toxicity in the overall cohort. Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 95.9%, 100%, 96.7%, and 100% at baseline and 6, 12, and 24 months after S-PBI, whereas patients scored the same periods as 86.5%, 97.1%, 95.1%, and 95.3%, respectively. The disagreement rates between MDs and patients during those periods were 9.4%, 2.9%, 1.6%, and 4.7%, respectively. There have been no recurrences or distant metastases. Conclusion: Dose was escalated to the target dose of 40 Gy in 5 fractions, with the occurrence of only 1 dose-limiting toxicity. Patients felt cosmetic results improved within the first year after surgery and stereotactic body radiation therapy. Our results show minimal toxicity with excellent cosmesis; however, further follow-up is warranted in future studies. This study is the first to show the safety, tolerability, feasibility, and cosmesis results of a 5-fraction dose-escalated S-PBI treatment for

Differences in Clinical Results After LINAC-Based Single-Dose Radiosurgery Versus Fractionated Stereotactic Radiotherapy for Patients With Vestibular Schwannomas

International Nuclear Information System (INIS)

Combs, Stephanie E.; Welzel, Thomas; Schulz-Ertner, Daniela; Huber, Peter E.; Debus, Juergen

2010-01-01

Purpose: To evaluate the outcomes of patients with vestibular schwannoma (VS) treated with fractionated stereotactic radiotherapy (FSRT) vs. those treated with stereotactic radiosurgery (SRS). Methods and Materials: This study is based on an analysis of 200 patients with 202 VSs treated with FSRT (n = 172) or SRS (n = 30). Patients with tumor progression and/or progression of clinical symptoms were selected for treatment. In 165 out of 202 VSs (82%), RT was performed as the primary treatment for VS, and for 37 VSs (18%), RT was conducted for tumor progression after neurosurgical intervention. For patients receiving FSRT, a median total dose of 57.6 Gy was prescribed, with a median fractionation of 5 x 1.8 Gy per week. For patients who underwent SRS, a median single dose of 13 Gy was prescribed to the 80% isodose. Results: FSRT and SRS were well tolerated. Median follow-up time was 75 months. Local control was not statistically different for both groups. The probability of maintaining the pretreatment hearing level after SRS with doses of ≤13 Gy was comparable to that of FSRT. The radiation dose for the SRS group (≤13 Gy vs. >13 Gy) significantly influenced hearing preservation rates (p = 0.03). In the group of patients treated with SRS doses of ≤13 Gy, cranial nerve toxicity was comparable to that of the FSRT group. Conclusions: FSRT and SRS are both safe and effective alternatives for the treatment of VS. Local control rates are comparable in both groups. SRS with doses of ≤13 Gy is a safe alternative to FSRT. While FSRT can be applied safely for the treatment of VSs of all sizes, SRS should be reserved for smaller lesions.

Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall

International Nuclear Information System (INIS)

Jebsen, Nina L.; Engellau, Jacob; Engström, Katarina; Bauer, Henrik C.; Monge, Odd R.; Muren, Ludvig P.; Eide, Geir E.; Trovik, Clement S.; Bruland, Øyvind S.

2013-01-01

Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence interval [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma

Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall

Energy Technology Data Exchange (ETDEWEB)

Jebsen, Nina L., E-mail: nina.louise.jebsen@helse-bergen.no [Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen (Norway); Department of Oncology, Haukeland University Hospital, Bergen (Norway); Engellau, Jacob [Department of Oncology, Skåne University Hospital, Lund (Sweden); Engström, Katarina [Department of Oncology, Sahlgrenska University Hospital, Gothenburg (Sweden); Bauer, Henrik C. [Department of Molecular Medicine and Surgery, Section for Orthopaedics and Sports Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm (Sweden); Monge, Odd R. [Department of Oncology, Haukeland University Hospital, Bergen (Norway); Muren, Ludvig P. [Department of Physics and Technology, University of Bergen, Bergen (Norway); Department of Medical Physics, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Eide, Geir E. [Centre for Clinical Research, Haukeland University Hospital, Bergen (Norway); Department of Public Health and Primary Health Care, University of Bergen, Bergen (Norway); Trovik, Clement S. [Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen (Norway); Department of Oncology, Haukeland University Hospital, Bergen (Norway); Bruland, Øyvind S. [Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Institute of Clinical Medicine, University of Oslo, Oslo (Norway)

2013-08-01

Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence interval [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma.

Intensification of antitumor radiation effect by metronidazole and short-term hyperglycemia and dependence of therapeutic effect on schedules of fractionation and value of single dose

International Nuclear Information System (INIS)

Venkhvadze, N.G.

1988-01-01

Combined application of metronidazole and short-term hyperglycemia under fractionated irradiation of sarcoma-45, 340 in white rats-males is studied. Tumors were γ-irradiated with 60 Co threefold in 48 hours at 15 Gy single dose or irradiated threefold in a week at 20, 25 and 30 Gy doses. Efficiency of experimental therapy is cheked by dynamics of tumor regression, a number of animals with tumors reabsorbed temporarily, a number of animals recovered and time of tumor grouth up to the initial volume. It is established that combined application of metronidazole and short-term hyperglycemia under fractionated irradiation increases essentially the efficiency of radiotherapy carried out by large fractions with great time intervals. 7 refs.; 1 fig.; 2 tabs

The Effects of Radiation and Dose-Fractionation on Cancer and Non-Tumor Disease Development

Directory of Open Access Journals (Sweden)

Gayle E. Woloschak

2012-12-01

Full Text Available The Janus series of radiation experiments, conducted from 1970 to 1992, explored the effects of gamma and neutron radiation on animal lifespan and disease development. Data from these experiments presents an opportunity to conduct a large scale analysis of both tumor and non-tumor disease development. This work was focused on a subset of animals from the Janus series of experiments, comparing acute or fractionated exposures of gamma or neutron radiation on the hazards associated with the development of tumor and non-tumor diseases of the liver, lung, kidney or vascular system. This study also examines how the co-occurrence of non-tumor diseases may affect tumor-associated hazards. While exposure to radiation increases the hazard of dying with tumor and non-tumor diseases, dose fractionation modulates these hazards, which varies across different organ systems. Finally, the effect that concurrent non-cancer diseases have on the hazard of dying with a tumor also differs by organ system. These results highlight the complexity in the effects of radiation on the liver, lung, kidney and vascular system.

SU-F-T-02: Estimation of Radiobiological Doses (BED and EQD2) of Single Fraction Electronic Brachytherapy That Equivalent to I-125 Eye Plaque: By Using Linear-Quadratic and Universal Survival Curve Models

Energy Technology Data Exchange (ETDEWEB)

Kim, Y; Waldron, T; Pennington, E [University Of Iowa, College of Medicine, Iowa City, IA (United States)

2016-06-15

Purpose: To test the radiobiological impact of hypofractionated choroidal melanoma brachytherapy, we calculated single fraction equivalent doses (SFED) of the tumor that equivalent to 85 Gy of I125-BT for 20 patients. Corresponding organs-at-risks (OARs) doses were estimated. Methods: Twenty patients treated with I125-BT were retrospectively examined. The tumor SFED values were calculated from tumor BED using a conventional linear-quadratic (L-Q) model and an universal survival curve (USC). The opposite retina (α/β = 2.58), macula (2.58), optic disc (1.75), and lens (1.2) were examined. The % doses of OARs over tumor doses were assumed to be the same as for a single fraction delivery. The OAR SFED values were converted into BED and equivalent dose in 2 Gy fraction (EQD2) by using both L-Q and USC models, then compared to I125-BT. Results: The USC-based BED and EQD2 doses of the macula, optic disc, and the lens were on average 118 ± 46% (p < 0.0527), 126 ± 43% (p < 0.0354), and 112 ± 32% (p < 0.0265) higher than those of I125-BT, respectively. The BED and EQD2 doses of the opposite retina were 52 ± 9% lower than I125-BT. The tumor SFED values were 25.2 ± 3.3 Gy and 29.1 ± 2.5 Gy when using USC and LQ models which can be delivered within 1 hour. All BED and EQD2 values using L-Q model were significantly larger when compared to the USC model (p < 0.0274) due to its large single fraction size (> 14 Gy). Conclusion: The estimated single fraction doses were feasible to be delivered within 1 hour using a high dose rate source such as electronic brachytherapy (eBT). However, the estimated OAR doses using eBT were 112 ∼ 118% higher than when using the I125-BT technique. Continued exploration of alternative dose rate or fractionation schedules should be followed.

Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

International Nuclear Information System (INIS)

Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E.

2015-01-01

Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm

Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

Energy Technology Data Exchange (ETDEWEB)

Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E., E-mail: claudia.ruebe@uks.eu

2015-08-01

Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm.

Misonidazole in fractionated radiotherapy: are many small fractions best

International Nuclear Information System (INIS)

Denekamp, J.; McNally, N.J.; Fowler, J.F.; Joiner, M.C.

1980-01-01

The largest sensitizing effect is always demonstrated with six fractions, each given with 2 g/m 2 of misonidazole. In the absence of reoxygenation a sensitizer enhancement ratio of 1.7 is predicted, but this falls to 1.1-1.2 if extensive reoxygenation occurs. Less sensitization is observed with 30 fractions, each with 0.4 g/m 2 of drug. However, for clinical use, the important question is which treatment kills the maximum number of tumour cells. Many of the simulations predict a marked disadvantage of reducing the fraction number for X rays alone. The circumstances in which this disadvantage is offset by the large Sensitizer enhancement ratio values with a six-fraction schedule are few. The model calculations suggest that many small fractions, each with a low drug dose, are safest unless the clinician has some prior knowledge that a change in fraction number is not disadvantageous. (author)

Radiation-induced lung damage in rats: The influence of fraction spacing on effect per fraction

International Nuclear Information System (INIS)

Haston, C.K.; Hill, R.P.; Newcomb, C.H.; Van Dyk, J.

1994-01-01

When the linear-quadratic model is used to predict fractionated treatments which are isoeffective, it is usually assumed that each (equal size) treatment fraction has an equal effect, independent of the time at which it was delivered during a course of treatment. Previous work has indicated that this assumption may not be valid in the context of radiation-induced lung damage in rats. Consequently the authors tested directly the validity of the assumption that each fraction has an equal effect, independent of the time it is delivered. An experiment was completed in which fractionated irradiation was given to whole thoraces of Sprague-Dawley rats. All treatment schedules consisted of eleven equal dose fractions in 36 days given as a split course, with some groups receiving the bulk of the doses early in the treatment schedule, before a 27-day gap, and others receiving most of the dose toward the end of the treatment schedule, after the time gap. To monitor the incidence of radiation-induced damage, breathing rate and lethality assays were used. The maximum differences in the LD 50 s and breathing rate ED 50 s for the different fractionation schedules were 4.0% and 7.7% respectively. The lethality data and breathing rate data were consistent with results expected from modelling using the linear-quadratic model with the inclusion of an overall time factor, but not the generalized linear-quadratic model which accounted for fraction spacing. For conventional daily fractionation, and within the range of experimental uncertainties, the results indicate that the effect of a treatment fraction does not depend on the time at which it is given (its position) in the treatment. The results indicate no need to extend isoeffect formulae to consider the effect of each fraction separately for radiation-induced lung damage. 21 refs., 6 figs., 3 tabs

Early fractionation methods and the origins of the NSD concept

International Nuclear Information System (INIS)

Thames, H.D. Jr.

1988-01-01

The concept of the time factor in radiotherapy originated in the controversy surrounding single-dose and fractionated treatments during the first 20 years of this century. The success of Coutard's fractionated treatments of larynx tumors was an important factor in the abandonment of single-dose treatments. There was considerable research afterwards into the influence of dose rate and overall time of treatment on the responses of normal tissues. Recovery was modeled in terms of the Schwarzschild law of photochemistry, as exemplified by the analysis of Strandqvist in log dose-log time coordinates. Different conventions were followed in defining the time for a single-dose treatment. Subsequently the concept arose that the slopes of isoeffect lines relating dose and treatment time for normal tissues and tumors were different and moreover that the effects of fraction number and overall time could be separated; these developments constituted the foundation of the Ellis NSD model. It had an important influence on clinical practice and was reasonably successful in predicting isoeffective regimens for acute effects. It failed to predict severe late effects after large dose fractions. The dissociation between acute and late effects with altered fractionation led to recognition of the importance of the ratio α/β in characterizing the fractionation sensitivity of tissues. (orig.) With 125 refs

The hemodynamic effects of spinal block with low dose of bupivacaine and sufentanil in patients with low myocardial ejection fraction.

Directory of Open Access Journals (Sweden)

Mehdi Sanatkar

2013-07-01

Full Text Available The aim of this study was to assess the effect of spinal block with low dose of bupivacaine and sufentanil on patients with low cardiac output who underwent lower limb surgery. Fifteen patients who had ejection fraction less than 40% (group 1 were compared with 65 cases with ejection fraction more than 40% (group 2 in our study. Our subjects underwent spinal block with 7.5 mg hyperbaric bupivacaine 0.5% and 5 µg sufentanil. We recorded early events such as hypotension, bradycardia, vasopressor need and ST segment change in our cases. The average mean arterial pressure decreased 13% (110 mmHg to 95.7 mmHg in group 1 and 20% (160 mmHg to 128 mmHg in group 2 (P<0.001. Hypotension due to spinal anesthesia was observed in none of our subjects in both groups and none of our cases need to vasopressor support. All patients remained alert, and no ST segment changes were observed in two groups. In our study none of subjects complained of pain intraoperatively. The subjects were without complaints during the spinal anesthetic in both groups. Spinal block with low dose local anesthetic and sufentanil was a safe and effective method for lower limb surgery in patients with low ejection fraction.

The kinetics of repair in mouse lung after fractionated irradiation

International Nuclear Information System (INIS)

Travis, E.L.; Thames, H.D.; Watkins, T.L.; Kiss, I.

1987-01-01

The kinetics of repair of sublethal damage in mouse lung was studied after fractionated doses of 137 Cs γ-rays. A wide range of doses per fraction (1.7-12 Gy) was given with interfraction intervals ranging from 0.5 to 24 h. Data were analysed by a direct method of analysis using the incomplete repair model. The half-time of repair (Tsub(1/2)) was 0.76 h for the pneumonitis phase of damage (up to 8 months) and 0.65 h for the later phase of damage up to 12 months. Rate of repair was dependent on fraction size for both phases of lung damage and was faster after large dose fractions than after small fractions. Tsub(1/2) was 0.6 h (95% c.1. 0.53, 0.69) for doses per fraction greater than 5 Gy and 0.83 h (95% c.1. 0.76, 0.92) for doses per fraction of 2 Gy. Repair was nearly complete by 6 h at least for the pneumonitis phase of damage. If extrapolated to humans, these results imply that treatments with multiple fractions per day involving the lung will not be limited by the necessity for interfraction intervals much longer than 6 h. (author)

Modification of UV-induced mutation frequencies in Chinese hamster- cells by dose fractionation, cycloheximide and caffeine treatments

International Nuclear Information System (INIS)

Chang, C.-C.; Schultz, R.; Trosko, J.E.; D'Ambrosio, S.M.; Setlow, R.B.

1978-01-01

Chinese hamster (V79) cells were irradiated with a fractionated regime of ultraviolet light (UV 1 +UV 2 ). The fractionation of a UV dose always increased the colony-forming ability but reduced (or it did not change) the mutation frequencies. Treatment with cycloheximide between the two UV irradiations resulted in two types of effects, depending on the protocols used. Long exposures to cycloheximide (i.e., >6h) for the entire period between UV 1 and UV 2 or partial treatment of cycloheximide (i.e., 3h) long before UV 2 always resulted in reduced colony-forming ability and enhanced or unchanged mutation frequencies. Exposure to cycloheximide for the entire period in the short fractionated regime (i.e., 4h) between UV 1 and UV 2 or partial treatment of cycloheximide just prior to UV 2 tended to give the opposite effects. Caffeine treatment before UV 2 , with or without UV 1 , significantly increased the mutation frequencies. These results suggest that an error-free postreplication repair system exists in Chinese hamster cells which is inhibitable by particular cycloheximide or caffeine treatments. (Auth.)

Adaptive fractionation therapy: I. Basic concept and strategy

International Nuclear Information System (INIS)

Lu Weiguo; Chen Mingli; Chen Quan; Ruchala, Kenneth; Olivera, Gustavo

2008-01-01

Radiotherapy is fractionized to increase the therapeutic ratio. Fractionation in conventional treatment is determined as part of the prescription, and a fixed fraction size is used for the whole course of treatment. Due to patients' day-to-day variations on the relative distance between the tumor and the organs at risk (OAR), a better therapeutic ratio may be attained by using an adaptive fraction size. Intuitively, we want to use a larger fraction size when OAR and the tumor are far apart and a smaller fraction size when OAR and the tumor are close to each other. The concept and strategies of adaptive fractionation therapy (AFT) are introduced in this paper. AFT is an on-line adaptive technique that utilizes the variations of internal structures to get optimal OAR sparing. Changes of internal structures are classified as different configurations according to their feasibility to the radiation delivery. A priori knowledge is used to describe the probability distribution of these configurations. On-line processes include identifying the configuration via daily image guidance and optimizing the current fraction size. The optimization is modeled as a dynamic linear programming problem so that at the end of the treatment course, the tumor receives the same planned dose while OAR receives less dose than the regular fractionation delivery. Extensive simulations, which include thousands of treatment courses with each course consisting of 40 fractions, are used to test the efficiency and robustness of the presented technique. The gains of OAR sparing depend on the variations on configurations and the bounds of the fraction size. The larger the variations and the looser the bounds are, the larger the gains will be. Compared to the conventional fractionation technique with 2 Gy/fraction in 40 fractions, for a 20% variation on tumor-OAR configurations and [1 Gy, 3 Gy] fraction size bounds, the cumulative OAR dose with adaptive fractionation is 3-8 Gy, or 7-20% less than that

Six fractions per week of external beam radiotherapy and high-dose-rate brachytherapy for carcinoma of the uterine cervix: A phase I/II study

International Nuclear Information System (INIS)

Yoon, Sang Min; Huh, Seung Jae; Park, Won; Lee, Jeung Eun; Park, Young Je; Nam, Hee Rim; Lim, Do Hoon; Ahn, Yong Chan

2006-01-01

Purpose: This study evaluated the treatment results of external beam radiotherapy administered in six fractions per week and high-dose-rate (HDR) brachytherapy for the treatment of cervical cancer. Methods and Materials: From July 2000 to July 2003, 43 patients were enrolled in this study. The patients received 45 Gy from a 10-MV photon beam using four-field box or anterior-posterior beams. Parametrial regions and the pelvic side walls were boosted with up to 50.4 Gy using a midline block. The daily fraction dose was 1.8 Gy administered in six-weekly fractions, from Monday to Saturday. HDR brachytherapy was also delivered at doses of 24 Gy to point A in six fractions twice a week. The median follow-up time was 37 months (range, 9-60 months). Results: The median overall treatment time was 51 days for all patients (range, 44-62 days). Thirty-four patients (79.1%) achieved complete remission and 8 (18.6%) achieved partial remission after radiotherapy. Locoregional recurrence occurred in 5 patients (11.6%), and a distant metastasis was encountered in 6 patients (13.9%). The 3-year overall survival, locoregional, and distant metastasis-free survival rates were 74.7%, 87.8%, and 84.7%, respectively. Grade 2 and 3 late rectal complications were encountered in 3 (6.5%) and 1 (2.2%), respectively. There were no Grade 3 late bladder complications. Conclusions: Six fractions per week of external beam radiotherapy and HDR brachytherapy is an effective treatment for patients with a carcinoma of the uterine cervix and can be used as a possible alternative to concomitant chemoradiotherapy in elderly patients or in patients with co-morbidity

Expression profiling of murine lung 70 days following exposure to fractionated or acute dose of 1.0 Gy 56Fe- particle irradiation

Data.gov (United States)

National Aeronautics and Space Administration — Irradiation of the K-rasLA1 mouse model with a fractionated dose of 1.0Gy 56Fe- particles increases the incidence of invasive carcinoma compared to unirradiated...

Fraction-variant beam orientation optimization for non-coplanar IMRT

Science.gov (United States)

O'Connor, Daniel; Yu, Victoria; Nguyen, Dan; Ruan, Dan; Sheng, Ke

2018-02-01

Conventional beam orientation optimization (BOO) algorithms for IMRT assume that the same set of beam angles is used for all treatment fractions. In this paper we present a BOO formulation based on group sparsity that simultaneously optimizes non-coplanar beam angles for all fractions, yielding a fraction-variant (FV) treatment plan. Beam angles are selected by solving a multi-fraction fluence map optimization problem involving 500-700 candidate beams per fraction, with an additional group sparsity term that encourages most candidate beams to be inactive. The optimization problem is solved using the fast iterative shrinkage-thresholding algorithm. Our FV BOO algorithm is used to create five-fraction treatment plans for digital phantom, prostate, and lung cases as well as a 30-fraction plan for a head and neck case. A homogeneous PTV dose coverage is maintained in all fractions. The treatment plans are compared with fraction-invariant plans that use a fixed set of beam angles for all fractions. The FV plans reduced OAR mean dose and D 2 values on average by 3.3% and 3.8% of the prescription dose, respectively. Notably, mean OAR dose was reduced by 14.3% of prescription dose (rectum), 11.6% (penile bulb), 10.7% (seminal vesicle), 5.5% (right femur), 3.5% (bladder), 4.0% (normal left lung), 15.5% (cochleas), and 5.2% (chiasm). D 2 was reduced by 14.9% of prescription dose (right femur), 8.2% (penile bulb), 12.7% (proximal bronchus), 4.1% (normal left lung), 15.2% (cochleas), 10.1% (orbits), 9.1% (chiasm), 8.7% (brainstem), and 7.1% (parotids). Meanwhile, PTV homogeneity defined as D 95/D 5 improved from .92 to .95 (digital phantom), from .95 to .98 (prostate case), and from .94 to .97 (lung case), and remained constant for the head and neck case. Moreover, the FV plans are dosimetrically similar to conventional plans that use twice as many beams per fraction. Thus, FV BOO offers the potential to reduce delivery time for non-coplanar IMRT.

A new way of adapting IMRT delivery fraction-by-fraction to cater for variable intrafraction motion

International Nuclear Information System (INIS)

Webb, S; Bortfeld, T

2008-01-01

In this paper a technique is presented for adaptive therapy to compensate for variable intrafraction tissue motion. So long as the motion can be measured or deduced for each fraction the technique modifies the fluence profile for the subsequent fractions in a repeatable cyclic way. The fluence modification is based on projecting the dose discrepancies between the cumulative delivered dose after each fraction and the expected planned dose at the same stage. It was shown that, in general, it is best to adapt the fluence profile to moving leaves that also have been modified to 'breathe' according to some regular default motion. However, it is important to point out that, if this regular default motion were to differ too much from the variable motion at each fraction, then the result can be worse than adapting to non-breathing leaves in a dynamic MLC technique. Furthermore, in general it should always be possible to improve results by starting the adaptation process with a constrained deconvolution of the regular default motion

Compliance to the prescribed dose and overall treatment time in five randomized clinical trials of altered fractionation in radiotherapy for head-and-neck carcinomas

International Nuclear Information System (INIS)

Khalil, Azza A.; Bentzen, Soeren M.; Bernier, Jacques; Saunders, Michele I.; Horiot, Jean-Claude; Bogaert, Walter van den; Cummings, Bernard J.; Dische, Stanley

2003-01-01

Purpose: To investigate compliance to the prescribed dose-fractionation schedule in five randomized controlled trials of altered fractionation in radiotherapy for head-and-neck carcinoma. Methods and Materials: Individual patient data from 2566 patients participating in the European Organization for Research and Treatment of Cancer (EORTC) 22791, EORTC 22811, EORTC 22851, Princess Margaret Hospital (PMH), and continuous hyperfractionated accelerated radiotherapy (CHART) head-and-neck trials were merged in the fractionation IMPACT (Intergroup Merger of Patient data from Altered or Conventional Treatment schedules) study database. The ideal treatment time was defined as the minimum time required to deliver a prescribed schedule. Compliance to the prescribed overall treatment time was quantified as the difference between the actual and the ideal overall time. An overall measure of compliance in an individual patient, the total dose lost (TDL), was calculated as the dose lost due to prolongation of therapy (assuming a D prolif of 0.64 Gy/day) plus the difference between the prescribed and the actual dose given. Results: The time in excess of the ideal ranged up to 97 days (average 3.9 days), and 25% of the patients had delays of 6 days or more. World Health Organization (WHO) performance status and nodal stage had a significant effect on TDL. TDL was significantly higher in the conventional than in the altered arm of the EORTC 22851 and CHART trials. In the PMH trial, TDL was significantly higher in the hyperfractionation than in the conventional arm. Centers participating in the three EORTC trials varied significantly in their compliance. There was a significant improvement in compliance in patients treated more recently. Conclusions: Even in randomized controlled trials, compliance to the prescribed radiation therapy schedule may be relatively poor, especially after conventional fractionation. This affects the interpretation of the outcome of these trials

Allogeneic bone marrow transplantation in adults after fractionated body irradiation and high dose cyclophosphamide

International Nuclear Information System (INIS)

Brinch, L.; Evensen, S.A.; Albrechtsen, D.; Egeland, T.; Solheim, B.G.; Rollag, H.; Naalsund, A.; Jacobsen, A.B.

1991-01-01

The authors present short and long-term results of allogeneic bone marrow transplantation after hyper-fractionated total body irradiation and high dose cyclophosphamide in ten patients treated for leukaemia during th period 1985-89. Three patients died from complications connected to the transplantation, while seven are living free from leukaemia 18 to 59 months after transplantation. Two patients need treatment for chronic graft versus host disease. Allogeneic bone marrow transplantation is expensive and risky. Close cooperation between clinicians and laboratory specialists is essential. The treatment increases long term survival and probably cures certain patients with leukaemia. Some of the patients will need treatment for chronic graft versus host disease and other late sequelae. 19 refs., 2 tabs

Radiosensitivity of Nicotiana protoplasts. Action on cell; cycle effects of low dose and fractionated irradiations; biological repair

International Nuclear Information System (INIS)

Magnien, E.

1981-10-01

Leaf protoplasts of Nicotiana plumbaginifolia and Nicotiana sylvestris demonstrate five main qualities: they can be maintained as haploid lines; they constitute starting populations with a remarkable cytological homogeneity; they show a transient initial lag-phase; they yield very high plating efficiencies and retain permanently a complete differentiation capacity; being derived of a cell wall, they appear well adapted for fusion experiments or enzymatic dosages. The resumption of mitotic activity was followed by cytophotometric measurements, labelling experiments, nuclear sizing and enzymatic assays. The action of 5 Gy gamma-ray irradiations delayed entrance in the S-phase, provoked an otherwise not verified dependency between transcription, translation and protein synthesis, increased nuclear volumes in the G2-phase, and slightly stimulated the activity of a repair enzyme. The plating efficiency was a sensitive end-point which allowed the evaluation of the biological effectiveness of low to medium radiation-doses after gamma-ray and fast neutron irradiations. The neutron dose-RBE relationship increased from 3 to 25 when the dose decreased from 5 Gy to 5 mGy. When fractionated into low single doses only, a neutron dose of 300 mGy markedly increased its biological effectiveness: this phenomenon could not be explained by cell progression, and necessitated additional hypotheses involving other mechanisms in the specific action of low radiation doses. Radiation-induced UDS was measured in presence of aphidicolin. A beta-like DNA-polymerase was shown to be definitely involved in nuclear repair synthesis [fr

The radiobiology of prostate cancer including new aspects of fractionated radiotherapy

International Nuclear Information System (INIS)

Fowler, Jack F.

2005-01-01

Total radiation dose is not a reliable measure of biological effect when dose-per-fraction or dose-rate is changed. Large differences in biological effectiveness (per gray) are seen between the 2 Gy doses of external beam radiotherapy and the large boost doses given at high dose-rate from afterloading sources. The effects are profoundly different in rapidly or slowly proliferating tissues, that is for most tumors versus late complications. These differences work the opposite way round for prostate tumors versus late complications compared with most other types of tumor. Using the Linear-Quadratic formula it is aimed to explain these differences, especially for treatments of prostate cancer. The unusually slow growth rate of prostate cancers is associated with their high sensitivity to increased fraction size, so a large number of small fractions, such as 35 or 40 'daily' doses of 2 Gy, is not an optimum treatment. Theoretical modeling shows a stronger enhancement of tumor effect than of late complications for larger (and fewer) fractions, in prostate tumors uniquely. Biologically Effective Doses and Normalized Total Doses (in 2 Gy fraction equivalents) are given for prostate tumor, late rectal reactions, and - a new development - acute rectal mucosa. Tables showing the change of fraction-size sensitivity (the alpha/beta ratio) with proliferation rates of tissues lead to the association of slow cell doubling times in prostate tumors with small alpha/beta ratios. Clinical evidence to confirm this biological expectation is reviewed. The alpha/beta ratios of prostate tumors appear to be as low as 1.5 Gy (95% confidence interval 1.3-1.8 Gy), in contrast with the value of about 10 Gy for most other types of tumor. The important point is that alpha/beta ratio=1.5 Gy appears to be significantly less than the alpha/beta ratio=3 Gy for late complications in rectal tissues. Such differences are also emerging from recent clinical results. From this important difference stems

Attached, unattached fraction of progeny concentrations and equilibrium factor for dose assessments from {sup 222}Rn and {sup 220}Rn

Energy Technology Data Exchange (ETDEWEB)

Singh, Parminder; Saini, Komal; Bajwa, Bikramjit Singh [Guru Nanak Dev University, Department of Physics, Amritsar, Punjab (India); Mishra, Rosaline; Sahoo, Bijay Kumar [Bhabha Atomic Research Centre, Radiological Physics and Advisory Division, Mumbai (India)

2016-08-15

In this study, measurements of indoor radon ({sup 222}Rn), thoron ({sup 220}Rn) and their equilibrium equivalent concentration (EEC) were carried out in 96 dwellings from 22 different villages situated in Hamirpur district, Himachal Pradesh, India, by using LR-115 type II-based pinhole twin cup dosimeters and deposition-based progeny sensors (DRPS/DTPS). The annual average indoor {sup 222}Rn and {sup 220}Rn concentrations observed in these dwellings were 63.82 and 89.59 Bq/m{sup 3}, respectively, while the average EEC (attached + unattached) for {sup 222}Rn and {sup 220}Rn was 29.28 and 2.74 Bq/m{sup 3}. For {sup 222}Rn (f{sub Rn}) and {sup 220}Rn (f{sub Tn}), the average values of unattached fraction were 0.11 and 0.09, respectively. The equilibrium factors for radon (F{sub Rn}) and thoron (F{sub Tn}) varied from 0.12 to 0.77 with an average of 0.50, and from 0.01 to 0.34 with an average of 0.05, respectively. The annual inhalation dose due to mouth and nasal breathing was calculated using dose conversion factors and unattached fractions. The indoor annual effective doses for {sup 222}Rn (AEDR) and {sup 220}Rn (AEDT) were found to be 1.92 and 0.83 mSv a{sup -1}, respectively. The values of {sup 222}Rn/{sup 220}Rn concentrations and annual effective doses obtained in the present study are within the safe limits as recommended by the International Commission on Radiological Protection for indoor dwelling exposure conditions. (orig.)

Spinal Cord Doses in Palliative Lung Radiotherapy Schedules

International Nuclear Information System (INIS)

Ffrrcsi, F.H.; Parton, C.

2006-01-01

Aim: We aim to check the safety of the standard palliative radiotherapy techniques by using the Linear quadratic model for a careful estimation of the doses received by the spinal cord, in all standard palliative lung radiotherapy fields and fractionation. Material and Methods: All patients surveyed at this prospective audit were treated with palliative chest radio-therapy for lung cancer over a period from January to June 2005 by different clinical oncology specialists within the department. Radiotherapy field criteria were recorded and compared with the recommended limits of the MRC trial protocols for the dose and fractionation prescribed. Doses delivered to structures off the field central axis were estimated using a standard CT scan of the chest. Dose estimates were made using an SLPLAN planning system. As unexpected spinal cord toxicity has been reported after hypo fractionated chest radiotherapy, a sagittal view was used to calculate the isodoses along the length of the spinal cord that could lie within the RT field. Equivalent dose estimates are made using the Linear Quadratic Equivalent Dose formula (LQED). The relative radiation sensitivity of spinal cord for myelopathy (the a/b dose) cord has been estimated as a/b = 1 Gy. Results: 17 Gy in 2 fraction and 39 Gy in 13 fraction protocols have spinal cord equivalent doses (using the linear-quadratic model) that lie within the conventional safe limits of 50 Gy in 25 fractions for the 100% isodose. However when the dosimetry is modelled for a 6 MV 100 cm isocentric linac in 3 dimensions, and altered separations and air space inhomogeneity are considered, the D-Max doses consistently fall above this limit on our 3 model patients. Conclusion: The 17 Gy in 2 fraction and 39 Gy in 13 fraction protocol would risk spinal cord damage if the radio therapist was unaware of the potential spinal cord doses. Alterative doses are suggested below 15.5 Gy/ 2 fractions (7 days apart) would be most acceptable

Perioperative fractionated high-dose rate brachytherapy for malignant bone and soft tissue tumors

International Nuclear Information System (INIS)

Koizumi, Masahiko; Inoue, Takehiro; Yamazaki, Hideya; Teshima, Teruki; Tanaka, Eiichi; Yoshida, Ken; Imai, Atsushi; Shiomi, Hiroya; Kagawa, Kazufumi; Araki, Nobuto; Kuratsu, Shigeyuki; Uchida, Atsumasa; Inoue, Toshihiko

1999-01-01

Purpose: To investigate the viability of perioperative fractionated HDR brachytherapy for malignant bone and soft tissue tumors, analyzing the influence of surgical margin. Methods and Materials: From July 1992 through May 1996, 16 lesions of 14 patients with malignant bone and soft tissue tumors (3 liposarcomas, 3 MFHs, 2 malignant schwannomas, 2 chordomas, 1 osteosarcoma, 1 leiomyosarcoma, 1 epithelioid sarcoma, and 1 synovial sarcoma) were treated at the Osaka University Hospital. The patients' ages ranged from 14 to 72 years (median: 39 years). Treatment sites were the pelvis in 6 lesions, the upper limbs in 5, the neck in 4, and a lower limb in 1. The resection margins were classified as intracapsular in 5 lesions, marginal in 5, and wide in 6. Postoperative fractionated HDR brachytherapy was started on the 4th-13th day after surgery (median: 6th day). The total dose was 40-50 Gy/7-10 fr/ 4-7 day (bid) at 5 or 10 mm from the source. Follow-up periods were between 19 and 46 months (median: 30 months). Results: Local control rates were 75% at 1 year and 48% in 2 years, and ultimate local control was achieved in 8 (50%) of 16 lesions. Of the 8 uncontrolled lesions, 5 (63%) had intracapsular (macroscopically positive) resection margins, and all the 8 controlled lesions (100%) had marginal (microscopically positive) or wide (negative) margins. Of the total, 3 patients died of both tumor and metastasis, 3 of metastasis alone, 1 of tumor alone, and 7 showed no evidence of disease. Peripheral nerve palsy was seen in one case after this procedure, but no infection or delayed wound healing caused by tubing or irradiation has occurred. Conclusion: Perioperative fractionated HDR brachytherapy is safe, well tolerated, and applicable to marginal or wide surgical margin cases

Fractional carbon dioxide laser versus low-dose UVA-1 phototherapy for treatment of localized scleroderma: a clinical and immunohistochemical randomized controlled study.

Science.gov (United States)

Shalaby, S M; Bosseila, M; Fawzy, M M; Abdel Halim, D M; Sayed, S S; Allam, R S H M

2016-11-01

Morphea is a rare fibrosing skin disorder that occurs as a result of abnormal homogenized collagen synthesis. Fractional ablative laser resurfacing has been used effectively in scar treatment via abnormal collagen degradation and induction of healthy collagen synthesis. Therefore, fractional ablative laser can provide an effective modality in treatment of morphea. The study aimed at evaluating the efficacy of fractional carbon dioxide laser as a new modality for the treatment of localized scleroderma and to compare its results with the well-established method of UVA-1 phototherapy. Seventeen patients with plaque and linear morphea were included in this parallel intra-individual comparative randomized controlled clinical trial. Each with two comparable morphea lesions that were randomly assigned to either 30 sessions of low-dose (30 J/cm 2 ) UVA-1 phototherapy (340-400 nm) or 3 sessions of fractional CO 2 laser (10,600 nm-power 25 W). The response to therapy was then evaluated clinically and histopathologically via validated scoring systems. Immunohistochemical analysis of TGF-ß1 and MMP1 was done. Patient satisfaction was also assessed. Wilcoxon signed rank test for paired (matched) samples and Spearman rank correlation equation were used as indicated. Comparing the two groups, there was an obvious improvement with fractional CO 2 laser that was superior to that of low-dose UVA-1 phototherapy. Statistically, there was a significant difference in the clinical scores (p = 0.001), collagen homogenization scores (p = 0.012), and patient satisfaction scores (p = 0.001). In conclusion, fractional carbon dioxide laser is a promising treatment modality for cases of localized morphea, with proved efficacy of this treatment on clinical and histopathological levels.

Repair in mouse lung of multifraction X rays and neutrons: extension to 40 fractions

International Nuclear Information System (INIS)

Parkins, C.S.; Fowler, J.F.

1985-01-01

Repair parameters were calculated from measurements of breathing rate and lethality at monthly intervals up to 17 months after irradiation with 1, 10, 20 or 40 equal fractions, down to 1.1 Gy of x-rays and 0.18 Gy of 3 MeV neutrons per fraction. Sparing of neutron damage was negligible when the neutron dose was divided into multiple fractions; progressively greater repair of lung damage was seen after increasing x-ray fractions. Significant increase in the iso-effect dose for 40 x-ray fractions was found compared with 20, even at two fractions per day at six hour intervals, as was the case in the 40 fraction experiment. Data were well fitted by the linear quadratic formula for response vs. dose per fraction and the ratio γ/β yielded values of approx. 3 Gy after x-rays and 30 to 40 Gy after neutron irradiation, not different from γ/β ratios found for up to 20 fractions. Single dose RBE was less than 2, increasing to about six at the lowest dose per fraction measured, agreeing with previous results. The ratio of the γ component for neutrons to that for x-rays was approx. 8, which is therefore the limiting RBE predicted for infinitely small fractional doses. (U.K.)

Radioimmunotherapy with Y-90-epratuzumab in patients with previously treated B-cell lymphoma. A fractionated dose-escalation study

International Nuclear Information System (INIS)

Linden, O.; Cavallin-Stahl, E.; Tennvall, J.; Hindorf, C.; Olsson, T.; Strand, S.E.; Stenberg, L.; Wingardh, K.

2002-01-01

Aim: Fractionated RIT may improve outcome by decreasing heterogeneity in absorbed dose and by increasing therapeutic window. The humanised anti-CD22 antibody, Epratuzumab, (Immunomedics, Inc., Morris Plains, NJ) can be given repeatedly with minimal risk of neutralising Ab (HAHA), making fractionated treatment with 90 Y-labelled epratuzumab possible. Materials and Methods: Patients with previously treated B-cell lymphoma received increasing number (2-4) of weekly infusions of 90 Y-epratuzumab. Patients received either 185 MBq/m 2 per infusion (group A), or, if they had a history of high-dose chemotherapy with stem-cell rescue, 92.5 MBq/m 2 per infusion (group B). The first infusion included 150 MBq of 111 Indium for scintigraphic verification of tumour targeting and dosimetry. 1.5 mg/kg epratuzumab was administered with each infusion. The treatment could be repeated once after 3 m. Results: Of 23 patients, 16 in group A and 6 in group B were evaluable for response. The RR in group A was 62% objective response (OR) and 25% CR/CRu. One patient in group B showed OR. OR was seen in aggressive and indolent lymphoma. Response was also long-lasting and event-free survival of patients showing CR/CRu was 14 to 25+ months. In group A all seven patient, receiving three infusions, showed less than grade 3 platelet and neutrophil toxicity, except for two patients suffering grade 3 neutropenia. Of five patients with 4 weekly infusions there were two patients with dose-limiting haematological toxicity (DLT), both recently treated with high dose cytosar before RIT. With criteria used the maximal tolerated dose was three infusions 185 MBq/m 2 . In group B no patient suffered DLT and one patient exhibited OR. Seven patients were retreated after 3 months with minor toxicity, but improvement in OR in two cases. No patient has developed HAHA. CD22 expression on tumour cells, as assessed by flow cytometry, is available in 18 of 22 patients. In group A, seven of eight patients with

Fractionation and protraction for radiotherapy of prostate carcinoma

International Nuclear Information System (INIS)

Brenner, David J.; Hall, Eric J.

1999-01-01

Purpose: To investigate whether current fractionation and brachytherapy protraction schemes for the treatment of prostatic cancer with radiation are optimal, or could be improved. Methods and Materials: We analyzed two mature data sets on radiotherapeutic tumor control for prostate cancer, one using EBRT and the other permanent seed implants, to extract the sensitivity to changes in fractionation of prostatic tumors. The standard linear-quadratic model was used for the analysis. Results: Prostatic cancers appear significantly more sensitive to changes in fractionation than most other cancers. The estimated α/β value is 1.5 Gy [0.8, 2.2]. This result is not too surprising as there is a documented relationship between cellular proliferative status and sensitivity to changes in fractionation, and prostatic tumors contain exceptionally low proportions of proliferating cells. Conclusions: High dose rate (HDR) brachytherapy would be a highly appropriate modality for treating prostate cancer. Appropriately designed HDR brachytherapy regimens would be expected to be as efficacious as low dose rate, but with added advantages of logistic convenience and more reliable dose distributions. Similarly, external beam treatments for prostate cancer can be designed using larger doses per fraction; appropriately designed hypofractionation schemes would be expected to maintain current levels of tumor control and late sequelae, but with reduced acute morbidity, together with the logistic and financial advantages of fewer numbers of fractions

Radiobiological effect of different irradiation fractionated regimens in human brain glioma

International Nuclear Information System (INIS)

Gai Xue; Yang Weizhi; Gao Li; Jiang Heng; Wang Mianrong; Shi Huizhen

2010-01-01

Objective: To evaluate the radiobiological effect of different irradiation fractionated regimens in human glioma cells (BT 325 cell line). Methods: The xenografts in Balb/c-nude mice were irradiated with different single and fractionated regimens. The single fraction dose was 10, 20, 30, 40 and 60 Gy, respectively. The fractionated regimens were 2 Gy x 5 fractions ( irradiated every day), and 3 Gy x 3 fractions (irradiated every other day), 3 Gy x 5 fractions (irradiated every day) and 4 Gy x 3 fractions (irradiated every other day), with total doses of 125 Gy, 114 Gy, 126 Gy and 112 Gy, respectively. The growth curve was used to evaluate the tumor doubling time. clonogenic assays was performed to draw the cell survival curve and analyze the radiobiological parameters with doses of 1, 2, 4, 6, 8 and 10 Gy. T 1/2 was measured by comet assay. Results: Tumor regression were not observed by single fraction irradiation, 2 Gy x 5 fractions and 3 Gy x 3 fractions irradiation regimens. The tumor regress was more significant with the increas of fraction dose. The 4 Gy x 3 fractions inhibited tumor more though not curing tumor. The cell doubling time of the BT 325 cell was 30. 16 h and the tumor doubling time of the xenograft was 43 days.When fitted with L-Q model, α was 0. 36 Gy -1 and β was 0. 057 Gy -2 . When fitted with the single-hit multi target model, D 0 was 1. 394 Gy, Dq was 2. 127 Gy and SF 2 was 0.714, respectively. The T 1/2 was 9.999 min. Conclusions: Glioma is a radioresistant tumor. Increase of the fraction dose improves recent effect.Further study is needed to control the tumor stem cells. (authors)

Radiation therapy of malignant melanomas: an evaluation of clinically used fractionation schemes

International Nuclear Information System (INIS)

Strauss, A.; Dritschilo, A.; Nathanson, L.; Piro, A.J.

1981-01-01

To assess the importance of radiation dose fraction size in the treatment of malignant melanomas, the records of 48 patients (83 sites) treated at Tufts-New England Medical Center from 1971 to 1979 have been retrospectively reviewed. During this period, the dose fractionation schemes evolved from standard fraction size to large-dose techniques. Radiation fraction size was observed to be the major factor in the clinical response of melanoma. Fractions of 600-800 rad resulted in the best overall response (80%). The rapid fractionation scheme of 800-400-400 rad on successive days resulted in intermediate response (58%) and may be useful for the palliative treatment of selected patients

Fractionation parameters for human tissues and tumors

International Nuclear Information System (INIS)

Thames, H.D.; Turesson, I.; Bogaert, W. van den

1989-01-01

Time-dose factors such as fractionation sensitivity (α/β) can sometimes be estimated from clinical data, when there is a wide variation in dose, fraction size, treatment time, etc. This report summarizes estimates of fractionation parameters derived from clinical results. Consistent with the animal data, α/β is higher for acutely responding than for late-responding normal tissues. While many human tumors seem to be characterized by high α/β values, there are exceptions (e.g. melanomas). Repair kinetics may be slower in human than in rodent skin and mucosa, but there are no hard and fast estimates of the repair halftime. Regeneration in head and neck tumors is equivalent to a daily dose of 1 Gy or less, while in the mucosa it is equivalent to approximately 1.8 Gy/day. (author)

Maximizing therapeutic gain with gemcitabine and fractionated radiation

International Nuclear Information System (INIS)

Mason, Kathy A.; Milas, Luka; Hunter, Nancy R.; Elshaikh, Mohamed; Buchmiller, Lara; Kishi, Kazushi; Hittelman, K. Walter; Ang, K. Kian

1999-01-01

Purpose/Objective: The nucleoside analogue gemcitabine inhibits cellular repair and repopulation, induces apoptosis, causes tumor growth delay, and enhances radiation-induced growth delay. After single doses of drug and radiation, maximum enhancement of tumor response was obtained when gemcitabine preceded radiation by at least 24 h. Conversely, the cellular radioresponse of the normal gastrointestinal epithelium was slightly protected when gemcitabine and radiation were separated by 24 h. This differential response created a time frame within which therapeutic gain could be maximized. In our present investigation, we sought to define the most therapeutically beneficial scheme of gemcitabine administration when combined with fractionated radiotherapy. Methods and Materials: C3Hf/Kam mice were given identical drug and radiation schedules of administration, and both normal tissue (jejunal mucosa) and tumor (Sa-NH) responses were measured. Irradiation was given once per day for 5 days in normal tissue and tumor growth delay studies and twice per day for the tumor cure endpoint. A total dose of 25 mg/kg gemcitabine was given i.p. in 1 of 3 schedules: a single dose of 25 mg/kg 24 h before the start of fractionated irradiation, 12.5 mg/kg 24 h before the first and third radiation doses, or 24 h before each of 5 radiation doses. Groups of mice bearing 7- or 8-mm diameter tumors were treated with gemcitabine alone or in combination with fractionated irradiation under ambient or hypoxic conditions. The survival response of the jejunal mucosa was quantified by the microcolony assay and histologically by quantifying apoptosis, mitosis, S-phase fraction, and crypt cellularity. Results: For tumor growth delay, dose-modifying factors (DMFs) were similar (1.34-1.46) for all 3 schedules of drug administration. In contrast, the response of the jejunum was strongly dependent on the schedule of gemcitabine administration. A single dose of gemcitabine before the start of fractionated

The effects of high dose and highly fractionated radiation on distraction osteogenesis in the murine mandible

International Nuclear Information System (INIS)

Monson, Laura A; Cavaliere, Christi M; Deshpande, Sagar S; Ayzengart, Alexander L; Buchman, Steven R

2012-01-01

The ability of irradiated tissue to support bony growth remains poorly defined, although there are anecdotal cases reported showing mixed results for the use of mandibular distraction osteogenesis after radiation for head and neck cancer. Many of these reports lack objective measures that would allow adequate analysis of outcomes or efficacy. The purpose of this experiment was to utilize a rat model of mandibular distraction osteogenesis after high dose and highly fractionated radiation therapy and to evaluate and quantify distracted bone formation under these conditions. Male Sprague–Dawley rats underwent 12 fractions of external beam radiation (48 Gray) of the left mandible. Following a two week recovery period, an external frame distractor was applied and gradual distraction of the mandible was performed. Tissue was harvested after a twenty-eight day consolidation period. Gross, radiologic and histological evaluations were undertaken. Those animals subjected to pre-operative radiation showed severe attenuation of bone formation including bone atrophy, incomplete bridging of the distraction gap, and gross bony defects or non-union. Although physical lengthening was achieved, the irradiated bone consistently demonstrated marked damaging effects on the normal process of distraction osteogenesis. This murine model has provided reliable evidence of the injurious effects of high dose radiation on bone repair and regeneration in distraction osteogenesis utilizing accurate and reproducible metrics. These results can now be used to assist in the development of therapies directed at mitigating the adverse consequences of radiation on the regeneration of bone and to optimize distraction osteogenesis so it can be successfully applied to post-oncologic reconstruction

Radiobiological arguments for and clinical possibilities of unconventional fractionating rhythms

International Nuclear Information System (INIS)

Herrmann, T.; Voigtmann, L.

1986-01-01

Radiobiological considerations are presented using unconventional fractionating rhythms. The aim of this method is to enlarge the therapeutic dimensions between maximum tumor destruction and most careful treatment of late responding cell systems. These late responding tissues show a very similar dose-time reaction, probably by reason of a causal injury on cells of the capillary endothelium. In linear-quadratic models for the estimation of the parameters of the number of fractions and total treatment period it becomes evident that a careful treatment of late responding tissue can be attained by reduction of the single dose per fraction. Because with partition of a total dose in several fractions at daily irradiation a longer repopulation period is available also for the tumor irradiations are presented, done repeatedly during the day. Accelerated fractionation (same fractionating number in reduced treatment period) are contrasted to hyperfractionation (increased fractionating number within the same total treatment period) and possibilities in application are suggested. (author)

The come-back of hypo fractionation?

International Nuclear Information System (INIS)

Cosset, J.M.

2005-01-01

Hypo-fractionation (i.e. the use of fewer higher fractional doses than usual) is not a new concept. It had actually been proposed in the early year of Radiotherapy by the German and Austrian specialists. In the seventy's, supported by the - wrong - hypotheses which gave birth to the NSD (Nominal Standard Dose), hypo-fractionation reappears. The consequential increase of late complications which was observed led the radiation oncologists to give up again using large doses per fraction, except for a few specific situations, such as palliative treatments. We are recently facing a new 'come-back' of hypo-fractionation, in particular for breast and prostate cancers. In the case of breast cancer, the aim is clearly to look for more 'convenience' for both the patients and the physicians, proposing shorter irradiation schedules including a lesser number of fractions. Some 'modestly' hypo-fractionated schemes have been proposed and used, without apparently altering the efficacy/toxicity ratio, but these results have been seriously questioned. As for prostate cancer, the situation is different, since in that case new radiobiological data are at the origin of the newly proposed hypo-fractionation schedules. A number of papers actually strongly suggested that the fractionation sensitivity of prostate cancer could be higher than the one of the tissues responsible for late toxicity (i.e the exact opposite of the classical dogma). Based on those data, several hypo-fractionated schemes have been proposed, with a few preliminary results looking similar to the ones obtained by the classical schedules. However, no randomized study is available so far, and a few recent radiobiological data are now questioning the new dogma of the high fractionation sensitivity of prostate cancer. For those two - frequent - cancers, it seems therefore that prudence should prevail before altering classical irradiation schedules which have proven their efficacy, while staying open to new concepts and

Some aspects of time-dose relationships

International Nuclear Information System (INIS)

Sugawara, Tadashi; Koito, Kazumitsu; Aihara, Toshinori

1985-01-01

One hundred thirty-seven patients with non-small cell lung cancers, 57 with oral cavity cancers and 98 with postoperative breast cancers treated with external radiotherapy from 1974 to 1980 were analyzed to determine optimal trends of time-dose relationships. Superiorities of fractionation factors were examined by comparing the relative local recurrence or expire rates among the subgroups prognostically homogenized in each entities of the diseases. Faborable fractionation factors for the former two diseases were those in which treatment was given in shortened over-all times, and frequently with low fraction dose to the considerably high daily dose. These results indicate the superiority of accelerated fractionation regime to conventional one in the treatment of those diseases. In contrast, any optimal trend was not found with postoperative breast cancers but total dose administered more than 43 Gy. (author)

Effect of fractionated radiation on multidrug resistance in human ovarian cancer

International Nuclear Information System (INIS)

Kong Dejuan; Liu Xiaodong; Liang Bing; Jia Lili; Ma Shumei

2012-01-01

Objective: To investigate the effect of different subtypes of fractionated doses on multidrug resistance in ovarian cancer cells. Methods: The human ovarian cancer cell lines SKOV3 and its drug-resistant subtype SKVCR were divided into four groups i.e., sham-irradiated, single dose (10 Gy), fractionated dose (2 Gy × 5) and multi-fractionated dose (1 Gy × 2 × 5). Cell sensitivity to vincristine (VCR), etoposide (VP-16), pirarubicin (THP) and cisplatin (DDP) was measured by MTT assay. Western blot was applied to detect the expression of P-gp after irradiation. Results: The doubling time of SKVCR was about 1.8-fold of that of SKOV3 cells. P-gp was expressed in SKVCR but not in SKOV3. IC 50 values of SKVCR were higher than those of SKOV3. To SKOV3 cells, single dose irradiation decreased cell sensitivity to THP and DDP and fractionated irradiation decreased cell sensitivity to VCR, THP and VP-16. Multi-fractionated irradiation decreased cell sensitivity to VP-16. In SKVCR cells, all these irradiation treatments increased cell sensitivity to VCR and VP-16 but not to DDP. In addition, single and fractionated irradiation decreased P-gp expression in SKVCR cells. Conclusions: Single, fractionated and multi-fractionated radiation induced chemotherapy resistance in SKOV3 cells, while reversed drug resistance to VCR and VP-16 in SKVCR cells. (authors)

The influence of single and fractionated dose external beam irradiation on injury-induced arterial smooth muscle cell proliferation

International Nuclear Information System (INIS)

Schaefer, U.; Micke, O.; Dorszewski, A.; Breithardt, G.; Willich, N.

1997-01-01

Purpose/Objective: Restenosis after catheter-based revascularization has been demonstrated to be primarily caused by smooth muscle cell proliferation. This study examined the effects of external beam irradiation on neointimal proliferation after external injury to the central artery of the rabbit ear. Materials and Methods: 40 male New Zealand White rabbits were used in this study. Crush lesions were performed on each ear under general anesthesia and bilateral auricular nerve blockade. A single dose of 12 Gy (n=10), 16 Gy (n=10), or 20 Gy (n=10) and a fractionated dose of 4 x 5 Gy (n=10) gamma radiation was delivered to the left or right central artery of the ear 24 hours after injury; the contralateral central artery served as control. All rabbits were sacrificed after twenty-one days and the central arteries of the ear were fixed for morphometric measurements. Results: Mean (± SD) neointimal area was 0.062 ± 0.005 mm 2 (12 Gy), 0.022 ± 0,005 mm 2 (16 Gy), 0,028 ± 0,006 mm 2 and 0.038 mm 2 ± 0,02 mm 2 (4 x 5 Gy) in irradiated arteries compared with 0,081 ± 0,009 mm 2 in the control group. Mean (±SD) luminal area was 0.049 ± 0.004 mm 2 (12 Gy), 0.059 ± 0.002 mm 2 (16 Gy), 0.072 ± 0,006 mm 2 (20 Gy) and 0.048 mm 2 ± 0,018 mm 2 (4 x 5 Gy) in irradiated arteries compared with 0,043 ± 0,008 mm 2 in the control group. The difference in neointimal and luminal area between control and irradiated arteries was significant (p<0.05) only for the 16 and 20 Gy group compared to control. Conclusion: We conclude that in this model, external beam X-ray irradiation was successful in reducing neointimal proliferation after injury of the central artery of the rabbit ear. The optimal dose seems to be a single dose of 16 Gy - 20 Gy. Only a less prominent effect was noted for a fractionated dose of 4 x 5 Gy. Whether this approach can be used successfully to inhibit restenosis in the clinical setting requires further investigation

Effect of fractionated X-ray doses on the hemogram and the protein formula of the mouse; Action de doses fractionnees de rayons X sur l'hemogramme et la formule proteique de la souris

Energy Technology Data Exchange (ETDEWEB)

Alix, D; Pierotti, Th [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

1965-07-01

The authors have studied the action of small doses of radiation on the system of mice. Irradiations was performed at doses of 50, 100, 150 or 200 R according to groups, either, as single dose or as fractionated doses. It was established that changes begin to become evident only after total exposure of 100 R. It occurs a decrease of cellular constituents and more often than not an increase of total proteins and {gamma}-globulins. (authors) [French] Les auteurs ont etudie l'action des faibles doses de radiation sur la souris. Des irradiations furent pratiquees a des doses totales de 50, 100, 150 ou 200 R suivant les lots, soit en dose unique, soit en doses fractionnees. Ils ont constate que les modifications ne commencent a apparaitre nettement qu'apres une exposition de 100 R au total. Elles se font dans le sens de la diminution pour les elements cellulaires, le plus souvent dans le sens de l'augmentation pour les proteines totales et les {gamma}-globulines. (auteurs)

Concurrent cisplatin, infusional fluorouracil, and conventionally fractionated radiation therapy in head and neck cancer: Dose-limiting mucosal toxicity

Energy Technology Data Exchange (ETDEWEB)

Denham, J.W.; Abbott, R.L. (Royal Adelaide Hospital (Australia))

1991-03-01

After a preliminary dose-finding study involving 12 patients with advanced or locally recurrent head and neck cancer, 27 patients were treated on a phase II protocol, using fluorouracil 350 mg/m2/d by continuous intravenous (IV) infusion over 5 days, followed on the sixth day by a 2-hour IV infusion of cisplatin 50 mg/m2, administered during the first and fourth weeks of radiation therapy to total doses between 60 and 64 Gy, using 2 Gy daily fractions. Eight of these 27 patients had American Joint Committee on Cancer Staging (AJCC) stage III disease, and 12 had stage IV disease. Four had recurrent disease after surgery. Three-year follow-up is now available. Twenty-one (77.8%) remitted completely following treatment, and 11 remain free of local and regional relapse at 3 years. Four have developed systemic metastases. Following successful salvage treatment in two cases, estimated determinate survival at 3 years is 64%. Acute toxicity was manageable with this regime. Eleven instances of grade 3 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) mucositis were observed, which caused interruptions to radiotherapy in only four cases. No late sequelae have so far been recorded. It is concluded that the protocol described is tolerable but probably did not cause a greater number of locoregional cures than would have been expected following conventional radiotherapy alone in this group of patients. The use of infusional fluorouracil with concurrent conventionally fractionated radiation therapy and cisplatin infusion results in mucositis that limits the dose of fluorouracil to levels that are probably subtherapeutic.

Clinical evaluation of the hypoxic cytotoxin tirapazamine (SR-4233): phase I experience with repeated dose administration during fractionated irradiation

International Nuclear Information System (INIS)

Hancock, Steven L.; Spencer, Sharon; Mariscal, Carol; Wooten, Ann; Wheeler, Richard; Brown, J. Martin; Fisher, Cheryl; Roemeling, Reinhard von

1996-01-01

Purpose: Regions of chronic or transient hypoxia are common in many human tumors and are thought to limit tumor cell killing and tumor control with conventional irradiation and some chemotherapeutic agents. Tirapazamine (3-amino-1,2,4-benzotriazine-1,4-di-N-oxide) forms a cytotoxic free radical during reductive metabolism in regions of hypoxia. In well oxygenated regions, the tirapazamine radical reacts with molecular oxygen to form the inactive parent drug. This results in markedly greater toxicity for hypoxic cells than for the well oxygenated cells that comprise most normal tissues. Tirapazamine increased the anti-tumor effects of single dose or fractionated irradiation or cis-platin chemotherapy in murine tumors,in vivo . This study evaluated the ability to repeat the administration of Tirapazamine during courses of fractionated irradiation in humans after an earlier phase I trial established a maximum tolerated dose of 390 mg per square meter of body surface area (mg/m 2 ) when given as a single dose with radiotherapy. Materials and Methods: Between December 1993 and August 1995 22 patients with locally advanced or metastatic tumors of varying histology, normal renal, hepatic, and hematologic functions, and Karnofsky performance status ≥ 60 received repeated doses of Tirapazamine during a planned, 6 weeks course of standardly fractionated radiotherapy. After anti-emetic treatment with ondansetron (32 mg) and dexamethasone (16 mg), Tirapazamine was administered during a 2 hour intravenous infusion that ended from 30 to 90 minutes before a radiation treatment. Patients were monitored for acute toxicity during the course of treatment and for a minimum of one month after radiotherapy. Results: The study was initiated with three, biweekly doses of Tirapazamine at 330 mg/m 2 . Four of 7 patients who initiated treatment at this dose refused the second (1 patient) or third dose of Tirapazamine (3 patients). Two of the three patients who received three doses

In vivo assessment of catheter positioning accuracy and prolonged irradiation time on liver tolerance dose after single-fraction 192Ir high-dose-rate brachytherapy

Directory of Open Access Journals (Sweden)

Kropf Siegfried

2011-09-01

Full Text Available Abstract Background To assess brachytherapy catheter positioning accuracy and to evaluate the effects of prolonged irradiation time on the tolerance dose of normal liver parenchyma following single-fraction irradiation with 192 Ir. Materials and methods Fifty patients with 76 malignant liver tumors treated by computed tomography (CT-guided high-dose-rate brachytherapy (HDR-BT were included in the study. The prescribed radiation dose was delivered by 1 - 11 catheters with exposure times in the range of 844 - 4432 seconds. Magnetic resonance imaging (MRI datasets for assessing irradiation effects on normal liver tissue, edema, and hepatocyte dysfunction, obtained 6 and 12 weeks after HDR-BT, were merged with 3D dosimetry data. The isodose of the treatment plan covering the same volume as the irradiation effect was taken as a surrogate for the liver tissue tolerance dose. Catheter positioning accuracy was assessed by calculating the shift between the 3D center coordinates of the irradiation effect volume and the tolerance dose volume for 38 irradiation effects in 30 patients induced by catheters implanted in nearly parallel arrangement. Effects of prolonged irradiation were assessed in areas where the irradiation effect volume and tolerance dose volume did not overlap (mismatch areas by using a catheter contribution index. This index was calculated for 48 irradiation effects induced by at least two catheters in 44 patients. Results Positioning accuracy of the brachytherapy catheters was 5-6 mm. The orthogonal and axial shifts between the center coordinates of the irradiation effect volume and the tolerance dose volume in relation to the direction vector of catheter implantation were highly correlated and in first approximation identically in the T1-w and T2-w MRI sequences (p = 0.003 and p p = 0.001 and p = 0.004, respectively. There was a significant shift of the irradiation effect towards the catheter entry site compared with the planned dose

Proliferation studies for different radiotherapy fractionation regimes

International Nuclear Information System (INIS)

Jones, L.

1996-01-01

Full text: This study was undertaken to investigate extended treatment schedules and compare the differences between schedules for highly proliferative tumours. Treatment schedules can be extended for various reasons e.g. public holidays, early side effects. For highly proliferative tumours this can dramatically reduce the effective dose delivered to the tumour. To deduce the most effective schedule fractionation regimes are compared to a common schedule so that the effects can be understood. Thus an equation to allow this to be done for the proliferative case has been derived. (i) The linear quadratic model with proliferation has been used to investigate the effect on biological effective dose (BED) when treatment schedules are extended. (ii) An equation was derived for comparison with a standard effective dose (SED) of 2Gy/fraction given daily 5 days per week, this is a common schedule in most radiotherapy centres. The SED equation derived for the proliferative case is where n 1 and n 2 are the number of fractions for the initial and equivalent schedules respectively, d 1 is the dose delivered per fraction for the initial schedules. T 1 is the time taken for the initial schedule (in days) and T p is the proliferation half life for the tumour involved. SEDs were calculated for the CHART regime of 36 fractions at 1.5 Gy in 12 days (Saunders et al. 1988, cited in Fowler J F, Brit. J. Radiol. 62: 679-694, 1989) and various other schedules. Late effects of these schedules and their standard equivalents were compared. The dose required to achieve the same BED when a treatment schedule is extended has been found to be quite large in some circumstances. For breast tumours a loss of 2Gy 10 BED to tumour occurs after ten days extension of treatment time (T p =12 days,T k =12 days). For head and neck tumours a loss of 2Gy 10 BED occurs after only three and a half days (T p =3 days). From these results it seems that an accelerated fractionation schedule would be advantageous

Radiation therapy of malignant melanomas: an evaluation of clinically used fractionation schemes

International Nuclear Information System (INIS)

Strauss, A.; Dritschilo, A.; Nathanson, L.; Piro, A.J.

1981-01-01

To assess the importance of radiation dose fraction size in the treatment of malignant melanomas, the records of 48 patients (83 sites) treated at Tufts-New England Medical Center from 1971 to 1979 have been retrospectively reviewed. During this period, the dose fractionation schemes evolved from standard fraction size to large-dose techniques. Radiation fraction size was observed to be the major factor in the clinical response of melanoma. Fractions of 600 to 800 rad resulted in the best overall response (80%). The rapid fractionation scheme of 800 to 400 to 400 rad on successive days resulted in intermediate response (58%) and may be useful for the palliative treatment of selected patients

Risk assessment of excess drug and sunscreen absorption via skin with ablative fractional laser resurfacing : optimization of the applied dose for postoperative care.

Science.gov (United States)

Chen, Wei-Yu; Fang, Chia-Lang; Al-Suwayeh, Saleh A; Yang, Hung-Hsu; Li, Yi-Ching; Fang, Jia-You

2013-09-01

The ablative fractional laser is a new modality used for surgical resurfacing. It is expected that laser treatment can generally deliver drugs into and across the skin, which is toxicologically relevant. The aim of this study was to establish skin absorption characteristics of antibiotics, sunscreens, and macromolecules via laser-treated skin and during postoperative periods. Nude mice were employed as the animal model. The skin received a single irradiation of a fractional CO2 laser, using fluences of 4-10 mJ with spot densities of 100-400 spots/cm(2). In vitro skin permeation using Franz cells was performed. Levels of skin water loss and erythema were evaluated, and histological examinations with staining by hematoxylin and eosin, cyclooxygenase-2, and claudin-1 were carried out. Significant signs of erythema, edema, and scaling of the skin treated with the fractional laser were evident. Inflammatory infiltration and a reduction in tight junctions were also observed. Laser treatment at 6 mJ increased tetracycline and tretinoin fluxes by 70- and 9-fold, respectively. A higher fluence resulted in a greater tetracycline flux, but lower skin deposition. On the other hand, tretinoin skin deposition increased following an increase in the laser fluence. The fractional laser exhibited a negligible effect on modulating oxybenzone absorption. Dextrans with molecular weights of 4 and 10 kDa showed increased fluxes from 0.05 to 11.05 and 38.54 μg/cm(2)/h, respectively. The optimized drug dose for skin treated with the fractional laser was 1/70-1/60 of the regular dose. The skin histology and drug absorption had recovered to a normal status within 2-3 days. Our findings provide the first report on risk assessment of excessive skin absorption after fractional laser resurfacing.

Hypericin photocytotoxicyty followed after fractionated light irradiation

International Nuclear Information System (INIS)

Sackova, V.; Kulikova, L.; Mikes, J.; Kleban, J.; Fedorocko, P.

2006-01-01

The present study demonstrates the in vitro effect of hypericin-mediated photodynamic therapy with fractionated light delivery. Cells were photosensitized with unequal light fractions separated by dark intervals (1 h, 6 h). The changes in survival, apoptosis and cell cycle were compared on HT-29 cells irradiated with a single light dose (12 J/cm 2 ) to the fractionated light delivery (1+11 J/cm 2 ) 24 h and 48 h after photodynamic treatment. It was found that a fractionated light regime with a longer dark period resulted in a decrease of hypericin photo-cytotoxicity. Cell survival was higher after light sensitization with a 6 h dark interval. DNA fragmentation occurred after a single light dose application, but in contrast no apoptotic DNA formation was detected with a 6 h dark pause. After fractionation the percentage of cells in G 1 phase of the cell cycle was increased, while the proportion of cells in the G 2 phase decreased as compared to a single light dose application i. e. both percentage of cells in G 1 and G 2 phase of cell cycle were near control levels. We presume that the longer dark interval after the irradiation of cells by first light dose makes them to resistant to the effect of the second illumination. These findings confirm that the light application scheme together with other photodynamic protocol components is crucial for the photo-cytotoxicity of hypericin. (authors)

Multiple anatomy optimization of accumulated dose

International Nuclear Information System (INIS)

Watkins, W. Tyler; Siebers, Jeffrey V.; Moore, Joseph A.; Gordon, James; Hugo, Geoffrey D.

2014-01-01

Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated

Multiple anatomy optimization of accumulated dose

Energy Technology Data Exchange (ETDEWEB)

Watkins, W. Tyler, E-mail: watkinswt@virginia.edu; Siebers, Jeffrey V. [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia 22908 and Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298 (United States); Moore, Joseph A. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland 21231 and Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298 (United States); Gordon, James [Henry Ford Health System, Detroit, Michigan 48202 and Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298 (United States); Hugo, Geoffrey D. [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298 (United States)

2014-11-01

Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.

Multiple anatomy optimization of accumulated dose.

Science.gov (United States)

Watkins, W Tyler; Moore, Joseph A; Gordon, James; Hugo, Geoffrey D; Siebers, Jeffrey V

2014-11-01

To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.

Calculation of the biological effect of fractionated radiotherapy: the importance of radiation-induced apoptosis

International Nuclear Information System (INIS)

Olsen, D.R.

1995-01-01

The total effect (TE) has been calculated for two different fractionation formalisms: the consecutive and repetitive fractionation mechanism, using a modified linear quadratic (LQ) model which includes the effect of apoptosis. For a given total dose, an increase in TE is seen when increasing the dose per fraction as well as the apoptotic fraction (F a ). Also, the TE increases with increasing α/β ratio (of the modified LQ model). The ratio of TE for tumour tissue and TE for late reacting tissue is calculated assuming the absence of apoptosis in late reacting tissue and a common value of α/β (of the modified LQ model). The biological effect ratio (BR) is higher for a large F a and low doses per fraction, than for large doses per fraction and a small F a . Assuming a consecutive fractionation mechanism, the TE formalism is unable to predict a log cell kill of more than 3 for β values of 0.010-0.028. It is less dependent on dose per fraction and F a than the repetitive fractionation mechanism. The biological effect ratio is only slightly higher than 1, and is less influenced by F a , dose per fraction and α/β ratio. A repetitive fractionation mechanism is also consistent with the preliminary results of published fractionation experiments. The calculations indicate that designing fractionation regimes for optimization of biological effect is a process where the role of apoptotic cell inactivation must be maximized, and where the influence of mitotic cell inactivation may be of less importance. (author)

Fractionated radiosurgery for 9L gliosarcoma in the rat brain

International Nuclear Information System (INIS)

Kim, Jae Ho; Khil, Mark S.; Kolozsvary, Andrew; Gutierrez, Jorge A.; Brown, Stephen L.

1999-01-01

Purpose: Fractionated radiosurgery is being carried out in the clinic to improve the therapeutic ratio of single-dose radiosurgery using various fractionation schemes. Because there is a paucity of experimental radiobiological data in the literature on the tumor response and late-responding normal tissue of critical intracranial structures to radiosurgery, the present animal study was designed to compare the response following a single high dose of radiation with that obtained from calculated fractionated doses of radiosurgery. Methods and Materials: Male Fischer rats with 9L gliosarcoma growing in their brains were stereotactically irradiated and assayed for the tumor control rate and brain tissue damage. The radiation dose needed for 50% tumor control (TCD 50 ) was used as the endpoint of the efficacy of radiosurgery. Normal brain damage was measured histologically following a period of time over 270 days. Histological evaluation included hematoxylin-eosin (H and E), Luxol fast blue and periodic acid Schiff (LFB/PAS) for the presence of myelin and glial fibrillary acidic protein (GFAP) for the assessment of astrocytic re-activity. The optical density of optic nerves and chiasms staining with LFB/PAS was quantitatively measured using a computer image analysis to assess the magnitude of demyelination. Results: Radiosurgery (RS) was found to be more effective in curing small tumors than large tumors. The dose required to control 50% of the tumored animals for 120 days was 24, 31, and 40 Gy for 2-, 6-, and 12-day-old tumors, respectively. Using 12-day-old brain tumors, two fractions of 23.5 Gy and three fractions of 18.5 Gy were found to be equivalent to the single dose of 35 Gy for tumor control. For normal brain damages, the visual pathways including optic nerves and chiasm were found to be highly radiosensitive structures. A single dose of 35 Gy produced 100% severe optic neuropathy. The fractionated RS regimens spared substantial optic nerve damage. Conclusion

Differential effects of fractionated X irradiation on mouse spermatogonial stem cells

NARCIS (Netherlands)

van der Meer, Y.; Huiskamp, R.; Davids, J. A.; de rooij, D. G.

1993-01-01

The response of spermatogonial stem cells to fractionated X irradiation was studied in the various stages of the spermatogenic cycle of the CBA mouse. Fractionated doses of 2 + 2, 1 + 3, and 3 + 1 Gy with a 24-h interval between the doses were compared with a single dose of 4 Gy. The numbers of

Synchronized dynamic dose reconstruction

International Nuclear Information System (INIS)

Litzenberg, Dale W.; Hadley, Scott W.; Tyagi, Neelam; Balter, James M.; Ten Haken, Randall K.; Chetty, Indrin J.

2007-01-01

Variations in target volume position between and during treatment fractions can lead to measurable differences in the dose distribution delivered to each patient. Current methods to estimate the ongoing cumulative delivered dose distribution make idealized assumptions about individual patient motion based on average motions observed in a population of patients. In the delivery of intensity modulated radiation therapy (IMRT) with a multi-leaf collimator (MLC), errors are introduced in both the implementation and delivery processes. In addition, target motion and MLC motion can lead to dosimetric errors from interplay effects. All of these effects may be of clinical importance. Here we present a method to compute delivered dose distributions for each treatment beam and fraction, which explicitly incorporates synchronized real-time patient motion data and real-time fluence and machine configuration data. This synchronized dynamic dose reconstruction method properly accounts for the two primary classes of errors that arise from delivering IMRT with an MLC: (a) Interplay errors between target volume motion and MLC motion, and (b) Implementation errors, such as dropped segments, dose over/under shoot, faulty leaf motors, tongue-and-groove effect, rounded leaf ends, and communications delays. These reconstructed dose fractions can then be combined to produce high-quality determinations of the dose distribution actually received to date, from which individualized adaptive treatment strategies can be determined

Multi-institutional phase I study of low-dose ultra-fractionated radiotherapy as a chemosensitizer for gemcitabine and erlotinib in patients with locally advanced or limited metastatic pancreatic cancer

International Nuclear Information System (INIS)

Konski, Andre; Meyer, Joshua E.; Joiner, Michael; Hall, Michael J.; Philip, Philip; Shields, Anthony; McSpadden, Erin; Choi, Minsig; Adaire, Beth; Duncan, Gail; Meropol, Neal J.; Cescon, Terrence P.; Cohen, Steven J.

2014-01-01

Purpose: Gemcitabine (G) has been shown to sensitize pancreatic cancer to radiotherapy but requires lower doses of G and thus delays aggressive systemic treatment, potentially leading to distant failure. We initiated a phase I trial combining ultra-fractionated low-dose radiotherapy with full dose G and erlotinib in the treatment of patients with advanced pancreatic cancer. Methods: Patients with locally advanced or metastatic pancreatic cancer confined to the abdomen and an ECOG performance status (PS) of 0–1 who had received 0–1 prior regimens (without G or E) and no prior radiotherapy were eligible. Patients were treated in 21 day cycles with G IV days 1 and 8, E once PO QD, and twice daily RT fractions separated by at least 4 h on days 1, 2, 8, and 9. Whole abdominal RT fields were used. Primary endpoint was to define dose limiting toxicity (DLT) and the maximum tolerated dose (MTD). Results: 27 patients (median age 64 years and 15 male) were enrolled between 11/24/08 and 4/12/12. 1 patient withdrew consent prior to receiving any protocol therapy. 17 patients had a PS of 1. The majority of patients were stage IV. One DLT was noted out of 7 patients at dose level (DL) 1. Subsequently no DLTs were noted in 3 patients each enrolled at DL2-4 or 11 patients in the expansion cohort. The majority of grade 3 toxicities were hematologic with 1 grade 5 bowel perforation in dose level 1 in cycle 4. Best response in 24 evaluable patients: PR (8), stable (15), PD 1. Median survival for the entire group was 9.1 months. Conclusion: This phase I study combining low-dose ultra-fractionated RT as a sensitizer to full dose G plus E was well tolerated with encouraging efficacy. This represents a novel strategy worthy of further investigation in advanced pancreatic cancer patients

Variability of Marker-Based Rectal Dose Evaluation in HDR Cervical Brachytherapy

International Nuclear Information System (INIS)

Wang Zhou; Jaggernauth, Wainwright; Malhotra, Harish K.; Podgorsak, Matthew B.

2010-01-01

In film-based intracavitary brachytherapy for cervical cancer, position of the rectal markers may not accurately represent the anterior rectal wall. This study was aimed at analyzing the variability of rectal dose estimation as a result of interfractional variation of marker placement. A cohort of five patients treated with multiple-fraction tandem and ovoid high-dose-rate (HDR) brachytherapy was studied. The cervical os point and the orientation of the applicators were matched among all fractional plans for each patient. Rectal points obtained from all fractions were then input into each clinical treated plan. New fractional rectal doses were obtained and a new cumulative rectal dose for each patient was calculated. The maximum interfractional variation of distances between rectal dose points and the closest source positions was 1.1 cm. The corresponding maximum variability of fractional rectal dose was 65.5%. The percentage difference in cumulative rectal dose estimation for each patient was 5.4%, 19.6%, 34.6%, 23.4%, and 13.9%, respectively. In conclusion, care should be taken when using rectal markers as reference points for estimating rectal dose in HDR cervical brachytherapy. The best estimate of true rectal dose for each fraction should be determined by the most anterior point among all fractions.

Radiation-included brachial plexus injury; Follow-up of two different fractionation schedules

Energy Technology Data Exchange (ETDEWEB)

Powell, S.; Cooke, J.; Parsons, C. (Royal Marsden Hospital, London (UK))

1990-07-01

All 449 breast cancer patients treated with post-operative radiotherapy to the breast and lymph nodes between 1982 and 1984 have been followed for 3-5.5 years. In this group two different fractionation schedules were used, one five times a fortnight and one daily, both over 6 weeks. The calculated dose to the brachial plexus was 45 Gy in 15 fractions or 5e Gy in 30 fractions. These schedules are equivalent doses using the standard NSD formula. The diagnosis of a brachial plexus injury was made clinically and computed tomography from recurrent disease. The actuarial incidence of a radiation-induced brachial plexus injury for the whole group was 4.9% at 5.5 years. No cases were seen in the first 10 months following radiotherapy. The incidence rises between 1 and 4 years and then starts to plateau. When the large fraction size group is compared with the small fraction size group the incidence at 5.5 years is 5.9% and 1.0%, respectively (p 0.09). Two different treatment techniques were used in this group but were not found to contribute to the probability of developing a brachial plexud injury. It is suggested that radiation using large doses per fraction are less well tolerated by the brachial plexus than small doses per fraction; a commonly used fractionation schedule such as 45 Gy in 15 fractions may give unacceptably high brachial plexus morbidity; and the of small doses per fraction or avoiding lymphatic irradiation is advocated. (author). 13 refs.; 6 figs.; 1 tab.

Fractionated radiosurgery for painful spinal metastases: DOSIS - a phase II trial

International Nuclear Information System (INIS)

Guckenberger, Matthias; Hawkins, Maria; Flentje, Michael; Sweeney, Reinhart A

2012-01-01

One third of all cancer patients will develop bone metastases and the vertebral column is involved in approximately 70% of these patients. Conventional radiotherapy with of 1–10 fractions and total doses of 8-30 Gy is the current standard for painful vertebral metastases; however, the median pain response is short with 3–6 months and local tumor control is limited with these rather low irradiation doses. Recent advances in radiotherapy technology – intensity modulated radiotherapy for generation of highly conformal dose distributions and image-guidance for precise treatment delivery – have made dose-escalated radiosurgery of spinal metastases possible and early results of pain and local tumor control are promising. The current study will investigate efficacy and safety of radiosurgery for painful vertebral metastases and three characteristics will distinguish this study. 1) A prognostic score for overall survival will be used for selection of patients with longer life expectancy to allow for analysis of long-term efficacy and safety. 2) Fractionated radiosurgery will be performed with the number of treatment fractions adjusted to either good (10 fractions) or intermediate (5 fractions) life expectancy. Fractionation will allow inclusion of tumors immediately abutting the spinal cord due to higher biological effective doses at the tumor - spinal cord interface compared to single fraction treatment. 3) Dose intensification will be performed in the involved parts of the vertebrae only, while uninvolved parts are treated with conventional doses using the simultaneous integrated boost concept. It is the study hypothesis that hypo-fractionated image-guided radiosurgery significantly improves pain relief compared to historic data of conventionally fractionated radiotherapy. Primary endpoint is pain response 3 months after radiosurgery, which is defined as pain reduction of ≥ 2 points at the treated vertebral site on the 0 to 10 Visual Analogue Scale. 60 patients

In vivo assessment of the tolerance dose of small liver volumes after single-fraction HDR irradiation

International Nuclear Information System (INIS)

Ricke, Jens; Seidensticker, Max; Luedemann, Lutz; Pech, Maciej; Wieners, Gero; Hengst, Susanne; Mohnike, Konrad; Cho, Chie Hee; Lopez Haenninen, Enrique; Al-Abadi, Hussain; Felix, Roland; Wust, Peter

2005-01-01

Purpose: To prospectively assess a dose-response relationship for small volumes of liver parenchyma after single-fraction irradiation. Methods and Materials: Twenty-five liver metastases were treated by computed tomography (CT)-guided interstitial brachytherapy. Magnetic resonance imaging was performed 1 day before and 3 days and 6, 12, and 24 weeks after therapy. MR sequences included T1-w gradient echo (GRE) enhanced by hepatocyte-targeted gadobenate dimeglumine. All MRI data sets were merged with 3D dosimetry data and evaluated by two radiologists. The reviewers indicated the border of hyperintensity on T2-w images (edema) or hypointensity on T1-w images (loss of hepatocyte function). Based on the total 3D data, a dose-volume histogram was calculated. We estimated the threshold dose for either edema or function loss as the D 90 , i.e., the dose achieved in at least 90% of the pseudolesion volume. Results: Between 3 days and 6 weeks, the extension of the edema increased significantly from the 12.9 Gy isosurface to 9.9 Gy (standard deviation [SD], 3.3 and 2.6). No significant change was detected between 6 and 12 weeks. After 24 weeks, the edematous tissue had shrunk significantly to 14.7 Gy (SD, 4.2). Three days postbrachytherapy, the D 90 for hepatocyte function loss reached the 14.9 Gy isosurface (SD, 3.9). At 6 weeks, the respective zone had increased significantly to 9.9 Gy (SD, 2.3). After 12 and 24 weeks, the dysfunction volume had decreased significantly to the 11.9 Gy and 15.2 Gy isosurface, respectively (SD, 3 and 4.1). Conclusions: The 95% interval from 7.6 to 12.2 Gy found as the minimal hepatocyte tolerance after 6 weeks accounts for the radiobiologic variations found in CT-guided brachytherapy, including heterogeneous dose rates by variable catheter arrays

Repair of skin damage during fractionated irradiation with gamma rays and low-LET carbon ions

International Nuclear Information System (INIS)

Ando, Koichi; Koike, Sachiko; Uzawa, Akiko; Takai, Nobuhiko; Fukawa, Takeshi; Furusawa, Yoshiya; Aoki, Mizuho; Hirayama, Ryoichi

2006-01-01

In clinical use of carbon-ion beams, a deep-seated tumor is irradiated with a Spread-Out Bragg peak (SOBP) with a high-linear energy transfer (LET) feature, whereas surface skin is irradiated with an entrance plateau, the LET of which is lower than that of the peak. The repair kinetics of murine skin damage caused by an entrance plateau of carbon ions was compared with that caused by photons using a scheme of daily fractionated doses followed by a top-up dose. Right hind legs received local irradiations with either 20 keV/μm carbon ions or γ rays. The skin reaction of the irradiated legs was scored every other day up to Day 35 using a scoring scale that consisted of 10 steps, ranging from 0.5 to 5.0. An isoeffect dose to produce a skin reaction score of 3.0 was used to obtain a total dose and a top-up dose for each fractionation. Dependence on a preceding dose and on the time interval of a top-up dose was examined using γ rays. For fractionated γ rays, the total dose linearly increased while the top-up dose linearly decreased with an increase in the number of fractions. The magnitude of damage repair depended on the size of dose per fraction, and was larger for 5.2 Gy than 12.5 Gy. The total dose of carbon ions with 5.2 Gy per fraction did not change till 2 fractions, but abruptly increased at the 3rd fraction. Factors such as rapid repopulation, induced repair and cell cycle synchronization are possible explanations for the abrupt increase. As an abrupt increase/decrease of normal tissue damage could be caused by changing the number of fractions in carbon-ion radiotherapy, we conclude that, unlike photon therapy, skin damage should be carefully studied when the number of fractions is changed in new clinical trials. (author)

Effects of low-dose fractionated external irradiation on metabolic and structural characteristics of rat thyroid

Energy Technology Data Exchange (ETDEWEB)

Nadolnik, L.; Niatsetskaya, Z. [Institute of Biochemistry, National Academy of Sciences of Belarus, Grodno (Belarus)

2006-07-01

Full text of publication follows: The problem of thyroid radiosensitivity to the effect of low dose external ionizing irradiation presently seems to be the least studied, and the experimental findings - the most contradictory. The aim of the work was to study the effects of long-term low-dose fractionated irradiation on the iodide metabolism and structure of the thyroid. Female Wistar rats weighing 140-160 g were irradiated 20 times (5 times a week, for 4 weeks) using a 60 Co installation. The single absorbed doses were 0.1, 0.25 and 0.5 Gy and the total ones - 2.0, 5.0 and 10.0 Gy, respectively. The animals were decapitated after 1 day, 4 and 24 weeks following the last irradiation. The thyroid tissue was used to assay for thyro-peroxidase (T.P.O.) activity as well as total, protein -bound and free iodide concentrations. Microscopic and morphometric examination of histologic thyroid preparations was carried out. Blood was assayed for thyroxin (T4) and triiodothyronine (T3) concentrations. After a day following the irradiation, the thyroid showed a pronounced increase in the concentration of total iodide (30.0-54.4%) as well in that of free (32.1-60.8%) and protein-bound ones (24.4-37.4%). The most pronounced iodide concentration elevation was noted in the 0.1 -Gy animals, with thyroid T.P.O. activity being raised by 48.0%. Only the 0.5 Gy-group had 1.4-1.5-fold reduced thyroid hormone levels. Four weeks after the irradiation, studied parameters of irradiated rats were brought back to the control values, except for the 0.5 Gy-group. However, after 24-weeks, the 0.5-and 0.25- irradiated rats experienced a 12-20% thyroid weight elevation in comparison with the control. The thyroid of these animals demonstrated reduced contents of total and free iodide as well as T.P.O. activity by 24.5 and 34.8%. The 0.1 Gy-group had a 1.7-fold increased T.P.O. activity. The concentration of the thyroid hormones was maintained diminished only in the 0.5 Gy -irradiated group. However

Consideration of margins for hypo fractionated radiotherapy

International Nuclear Information System (INIS)

Herschtal, A.; Foroudi, F.; Kron, T.

2010-01-01

Full text: Geographical misses of the tumour are of concern in radiotherapy and are typically accommodated by introducing margins around the target. However, there is a trade-off between ensuring the target receives sufficient dose and minimising the dose to surrounding normal structures. Several methods of determining margin width have been developed with the most commonly used one proposed by M. VanHerk (VanHerk UROBP 52: 1407, 2002). VanHerk's model sets margins to achieve 95% of dose coverage for the target in 90% of patients. However, this model was derived assuming an infinite number of fractions. The aim of the present work is to estimate the modifications necessary to the model if a finite number of fractions are given. Software simulations were used to determine the true probability of a patient achieving 95% target coverage if different fraction numbers are used for a given margin width. Model parameters were informed by a large data set recently acquired at our institution using daily image guidance for prostate cancer patients with implanted fiducial markers. Assuming a 3 mm penumbral width it was found that using the VanHerk model only 74 or 54% of patients receive 95% of the prescription dose if 20 or 6 fractions are given, respectively. The steep dose gradients afforded by IMRT are likely to make consideration of the effects of hypofractionation more important. It is necessary to increase the margins around the target to ensure adequate tumour coverage if hypofractionated radiotherapy is to be used for cancer treatment. (author)

The relationship between sol fraction and radiation dose in radiation crosslinking of low-density polyethylene (LDPE)/ethylenevinylacetate copolymer (EVA) blend

International Nuclear Information System (INIS)

Zhang, W.X.; Liu, Y.T.; Sun, J.Z.

1990-01-01

In this paper, two different methods were used to prepare the blend of low-density polyethylene (LDPE) and ethylene vinyl acetate copolymer (EVA). One of them was mechanical blending, and the other was solution blending. The relationship between sol fraction and radiation dose of different weight ratio polymer blends has been studied. The method to calculate the β b value of polymer blend system (LDPE/EVA) has been established. (author)

Dosimetric evaluation of multi-pattern spatially fractionated radiation therapy using a multi-leaf collimator and collapsed cone convolution superposition dose calculation algorithm

Energy Technology Data Exchange (ETDEWEB)

Stathakis, Sotirios [Department of Radiation Oncology, University of Texas Health Science Center San Antonio, 7979 Wurzbach Rd, San Antonio, TX 78229 (United States)], E-mail: stathakis@uthscsa.edu; Esquivel, Carlos; Gutierrez, Alonso N.; Shi, ChengYu; Papanikolaou, Niko [Department of Radiation Oncology, University of Texas Health Science Center San Antonio, 7979 Wurzbach Rd, San Antonio, TX 78229 (United States)

2009-10-15

Purpose: In this paper, we present an alternative to the originally proposed technique for the delivery of spatially fractionated radiation therapy (GRID) using multi-leaf collimator (MLC) shaped fields. We employ the MLC to deliver various pattern GRID treatments to large solid tumors and dosimetrically characterize the GRID fields. Methods and materials: The GRID fields were created with different open to blocked area ratios and with variable separation between the openings using a MLC. GRID designs were introduced into the Pinnacle{sup 3} treatment planning system, and the dose was calculated in a water phantom. Ionization chamber and film measurements using both Kodak EDR2 and Gafchromic EBT film were performed in a SolidWater phantom to determine the relative output of each GRID design as well as its spatial dosimetric characteristics. Results: Agreement within 5.0% was observed between the Pinnacle{sup 3} predicted dose distributions and the measurements for the majority of experiments performed. A higher magnitude of discrepancy (15%) was observed using a high photon beam energy (18 MV) and small GRID opening. Skin dose at the GRID openings was higher than the corresponding open field by a factor as high as three for both photon energies and was found to be independent of the open-to-blocked area ratio. Conclusion: In summary, we reaffirm that the MLC can be used to deliver spatially fractionated GRID therapy and show that various GRID patterns may be generated. The Pinnacle{sup 3} TPS can accurately calculate the dose of the different GRID patterns in our study to within 5% for the majority of the cases based on film and ion chamber measurements. Disadvantages of MLC-based GRID therapy are longer treatment times and higher surface doses.

Response of the skin of hamsters to fractionated irradiation with X rays or accelerated carbon ions

International Nuclear Information System (INIS)

Leith, J.T.; Powers-Risius, P.; Woodruff, K.H.; McDonald, M.; Howard, J.

1981-01-01

The ventral thoracic skin of hamsters was irradiated with either single, split (two fractions given in 24 hr), or multiple (five fractions given daily) exposures of X rays or accelerated carbon ions using a 4-cm spread Bragg peak. Animals were positioned in the heavy-ion beam so that the ventral thoracic skin surface was 1 cm distal to the proximal peak of the modified beam. Early skin reactions from 6 to 30 days postirradiation were assessed. Using the average skin reactions produced in this period, it was found that the relative biological effect (RBE) for single doses of carbon ions was about 1.6 (5-17 Gy per fraction), for two fractions about 1.8 (5-17 Gy perfraction), and for five fractions about 1.9 (2.4-7.2 Gy per fraction). The fractional amount of sublethal damage repaired after carbon ion irradiation was about 0.3 (at dose levels of 2.4-8.0 Gy per fraction) compared to a value of about 0.45 (at dose levels of 60-13.0 Gy per fraction) found for the fractionated X irradiations, indicting about a 33% decrease in the relative amount of sublethal damage repaired after carbon ion irradiation in this position in the spread Bragg curve. Also, data were interpreted using plots of the reciprocal total dose needed to produce a given level of skin damage versus the dose per fraction used in the multifraction experiments, and of the RBE versus dose per fraction obtained from a nonparametric analysis of the responses. These approaches allow estimation of RBE at dose levels relevant to the clinical situation. Also, estimation may be made of the maximum permissible RBE by using the zero dose intercept value from the linear reciprocal dose plot. With this approach, the RBE at a dose level of 2 Gy is about 2.5 and the maximum RBE value is about 2.7

Morphological correlates of fractionated radiation of the mouse lung: Early and late effects

International Nuclear Information System (INIS)

Penney, D.P.; Siemann, D.W.; Rubin, P.; Maltby, K.

1994-01-01

The definition and quantitation of radiation-induced morphologic alterations in murine lungs is presented. The extent of injury to the lung, which is the dose-limiting organ in the thorax, may be reduced by fractionating the total radiation exposure to permit partial repair of radiation-induced damage between fraction administration and also to permit a larger total exposure to be administered. The authors previously reported that, following fractionated radiation exposures, as the dose/fraction decreases, the total dose to reach an isoeffect increases, with an α/β ratio of 3.2 and 3.0 for breathing rates and lethality, respectively. In the present report, they provide comparative morphologic evaluation of the effects of weekly fractionated, daily fractionated, and hyperfractionated radiation exposures. The doses administered within each group were uniform. To determine morphologic alterations, LAF1 mice were irradiated with 3, 15, and 30 fractions delivered in 19 days overall treatment time. In the hyperfractionation schedule, the two fractions per day were separated by a 6-h time interval. Total doses were as follows: 15-21 Gy for weekly fractionation, 30-41.5 Gy for daily fractionation, and 30-49.5 Gy for hyperfractionated schedules. Lung tissue, recovered either 24 or 72 weeks following the final exposure, was evaluated by transmission and scanning electron microscopy and light microscopy. Morphological damage was not uniform throughout the exposed lung and tended to be concentrated in lobes or portions of lobes. In the three fractionation regimens studied, there is progressive sparing of the lung with increased fractionation during the pnuemonitic state (24 weeks postirradiation). Both daily and twice daily fractionations provide increased sparing over weekly fractionation during the fibrotic stages (72 weeks postirradiation), but were not markedly different from each other (i.e. weekly < daily = twice daily). 41 refs., 15 figs., 2 tabs

High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma

Energy Technology Data Exchange (ETDEWEB)

Jani, Ashish; Shaikh, Fauzia; Barton, Sunjay [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States); Willis, Callen [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Banerjee, Debarshi [Department of Pediatrics, Columbia University Medical Center, New York, New York (United States); Mitchell, Jason [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Hernandez, Sonia L. [Department of Surgery, University of Chicago, Chicago, Illinois (United States); Hei, Tom [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States); Kadenhe-Chiweshe, Angela [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Yamashiro, Darrell J. [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Department of Pediatrics, Columbia University Medical Center, New York, New York (United States); Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York (United States); Connolly, Eileen P., E-mail: epc2116@cumc.columbia.edu [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States)

2016-04-01

Purpose: To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)–pericyte interaction as a potential target for combined treatment with antiangiogenic agents. Methods and Materials: The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed. Results: HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis of tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours. Conclusions: HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.

Fractionated stereotactic radiation therapy and single high-dose radiosurgery for acoustic neuroma: early results of a prospective clinical study

International Nuclear Information System (INIS)

Meijer, O.W.M.; Wolbers, J.G.; Baayen, J.C.; Slotman, B.J.

2000-01-01

Purpose: To prospectively assess the local control and toxicity rate in acoustic neuroma patients treated with linear accelerator-based radiosurgery and fractionated stereotactic radiation therapy. Methods and Materials: We evaluated 37 consecutive patients treated with stereotactic radiation therapy for acoustic neuroma. All patients had progressive tumors, progressive symptoms, or both. Mean tumor diameter was 2.3 cm (range 0.8-3.3) on magnetic resonance (MR) scan. Dentate patients were given a dose of 5 x 4 Gy or 5 x 5 Gy and edentate patients were given a dose of 1 x 10 Gy or 1 x 12.50 Gy prescribed to the 80% isodose. All patients were treated with a single isocenter. Results: With a mean follow-up period of 25 months (range 12-61), the actuarial local control rate at 5 years was 91% (only 1 patient failed). The actuarial rate of hearing preservation at 5 years was 66% in previously-hearing patients. The actuarial rate of freedom from trigeminal nerve toxicity was 97% at 5 years. No patient developed facial nerve toxicity or other complications. Conclusion: In this unselected series, fractionated stereotactic radiation therapy and linear accelerator-based radiosurgery give excellent local control in acoustic neuroma. It combines a high rate of preservation of hearing with a very low rate of other toxicity, although follow-up is relatively short

The response of mouse skin and lung to fractionated x-rays

International Nuclear Information System (INIS)

Field, S.B.; Hornsey, S.

1975-01-01

The relationship between total dose and number of fractions has been investigated for damage to lung and skin in mice. Single doses and various numbers of fractions have been given and the results are analysed in two ways: (i) by comparing the fractionated treatment with a single dose. With this approach, and assuming that the observed damage to lung and skin is the result of cell killing, it is estimated that the ratio of initial to final slope of the cell survival curve is about 7:1; (ii) by measuring the additional dose required when the number of fractions is doubled. These results are roughly fitted by a single-hit times multitarget survival-curve model, with the ratio of slopes about 3:1. It is concluded from this discrepancy that the two-component model is an inadequate description of the survival curve for the cells of either skin or lung. (author)

Quality control of 192Ir high dose rate after loading brachytherapy dose veracity

International Nuclear Information System (INIS)

Feng Zhongsu; Xu Xiao; Liu Fen

2008-01-01

Recently, 192 Ir high dose rate (HDR) afterloading are widely used in brachytherapy. The advantage of using HDR systems over low dose rate systems are shorter treatment time and higher fraction dose. To guarantee the veracity of the delivery dose, several quality control methods are deseribed in this work. With these we can improve the position precision, time precision and dose precision of the brachytherapy. (authors)

Modulation of haemopoietic radiation response of mice by diclofenac in fractionated treatment

International Nuclear Information System (INIS)

Hofer, M.; Pospisil, M.; Pipalova, I.; Hola, J.

1996-01-01

The effects were studied of diclofenac, an inhibitor of prostaglandin synthesis, on the acute radiation syndrome elicited in mice by fractionated irradiation. Several hematological parameters were evaluated in mice irradiated with 5x 2 Gy and 3x, 4x, or 5x 3 Gy (intervals between fractions 24 h) from a 60 Co gamma source. The animals were treated with diclofenac either before each fraction or only once before the last fraction. The survival of mice was recorded after the irradiation regimen of 5x 3 Gy followed by a ''top-up'' dose of 3.5 Gy given 24 h after the last radiation fraction. Statistically significant enhancement of the endogenous spleen colony and of leukopoiesis was found in mice treated with diclofenac repeatedly, as compared with both saline-treated irradiated controls and animals administered a single diclofenac dose, if a sublethal total radiation dose had been accumulated. However, following accumulation of a lethal radiation dose, slightly impaired survival was observed in mice given diclofenac. It follows from the results that diclofenac is a suitable drug for enhancing leukopoisesis impaired by sublethal fractionated irradiation. Nevertheless, the undesirable side effects of this drug affect adversely the survival of the experimental animals following a lethal accumulated radiation dose. 3 tabs., 3 figs.,32 refs

Effect of simultaneous, single oral doses of beta-carotene with lutein or lycopene on the beta-carotene and retinyl ester responses in the triacylglycerol-rich lipoprotein fraction of men

NARCIS (Netherlands)

Berg, H. van den; Vliet, T. van

1998-01-01

The effects of lutein and lycopene on β-carotene absorption and cleavage were investigated in 12 male subjects. Responses of carotenoids and retinyl palmitate in the triacylglycerol-rich lipoprotein (TRL) fraction after a separate 15-mg β-carotene dose were compared with those after a dose of 15 mg

Impact of Drug Therapy, Radiation Dose, and Dose Rate on Renal Toxicity Following Bone Marrow Transplantation

International Nuclear Information System (INIS)

Cheng, Jonathan C.; Schultheiss, Timothy E.; Wong, Jeffrey Y.C.

2008-01-01

Purpose: To demonstrate a radiation dose response and to determine the dosimetric and chemotherapeutic factors that influence the incidence of late renal toxicity following total body irradiation (TBI). Methods and Materials: A comprehensive retrospective review was performed of articles reporting late renal toxicity, along with renal dose, fractionation, dose rate, chemotherapy regimens, and potential nephrotoxic agents. In the final analysis, 12 articles (n = 1,108 patients), consisting of 24 distinct TBI/chemotherapy conditioning regimens were included. Regimens were divided into three subgroups: adults (age ≥18 years), children (age <18 years), and mixed population (both adults and children). Multivariate logistic regression was performed to identify dosimetric and chemotherapeutic factors significantly associated with late renal complications. Results: Individual analysis was performed on each population subgroup. For the purely adult population, the only significant variable was total dose. For the mixed population, the significant variables included total dose, dose rate, and the use of fludarabine. For the pediatric population, only the use of cyclosporin or teniposide was significant; no dose response was noted. A logistic model was generated with the exclusion of the pediatric population because of its lack of dose response. This model yielded the following significant variables: total dose, dose rate, and number of fractions. Conclusion: A dose response for renal damage after TBI was identified. Fractionation and low dose rates are factors to consider when delivering TBI to patients undergoing bone marrow transplantation. Drug therapy also has a major impact on kidney function and can modify the dose-response function

A model to accumulate fractionated dose in a deforming organ

International Nuclear Information System (INIS)

Yan Di; Jaffray, D.A.; Wong, J.W.

1999-01-01

Purpose: Measurements of internal organ motion have demonstrated that daily organ deformation exists throughout the course of radiation treatment. However, a method of constructing the resultant dose delivered to the organ volume remains a difficult challenge. In this study, a model to quantify internal organ motion and a method to construct a cumulative dose in a deforming organ are introduced. Methods and Materials: A biomechanical model of an elastic body is used to quantify patient organ motion in the process of radiation therapy. Intertreatment displacements of volume elements in an organ of interest is calculated by applying an finite element method with boundary conditions, obtained from multiple daily computed tomography (CT) measurements. Therefore, by incorporating also the measurements of daily setup error, daily dose delivered to a deforming organ can be accumulated by tracking the position of volume elements in the organ. Furthermore, distribution of patient-specific organ motion is also predicted during the early phase of treatment delivery using the daily measurements, and the cumulative dose distribution in the organ can then be estimated. This dose distribution will be updated whenever a new measurement becomes available, and used to reoptimize the ongoing treatment. Results: An integrated process to accumulate dosage in a daily deforming organ was implemented. In this process, intertreatment organ motion and setup error were systematically quantified, and incorporated in the calculation of the cumulative dose. An example of the rectal wall motion in a prostate treatment was applied to test the model. The displacements of volume elements in the rectal wall, as well as the resultant doses, were calculated. Conclusion: This study is intended to provide a systematic framework to incorporate daily patient-specific organ motion and setup error in the reconstruction of the cumulative dose distribution in an organ of interest. The realistic dose

COMMERCIAL SNF ACCIDENT RELEASE FRACTIONS

Energy Technology Data Exchange (ETDEWEB)

S.O. Bader

1999-10-18

The purpose of this design analysis is to specify and document the total and respirable fractions for radioactive materials that are released from an accident event at the Monitored Geologic Repository (MGR) involving commercial spent nuclear fuel (CSNF) in a dry environment. The total and respirable release fractions will be used to support the preclosure licensing basis for the MGR. The total release fraction is defined as the fraction of total CSNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. The radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses. This subset of the total release fraction is referred to as the respirable release fraction. Potential accidents may involve waste forms that are characterized as either bare (unconfined) fuel assemblies or confined fuel assemblies. The confined CSNF assemblies at the MGR are contained in shipping casks, canisters, or disposal containers (waste packages). In contrast to the bare fuel assemblies, the container that confines the fuel assemblies has the potential of providing an additional barrier for diminishing the total release fraction should the fuel rod cladding breach during an accident. However, this analysis will not take credit for this additional bamer and will establish only the total release fractions for bare unconfined CSNF assemblies, which may however be

COMMERCIAL SNF ACCIDENT RELEASE FRACTIONS

International Nuclear Information System (INIS)

S.O. Bader

1999-01-01

The purpose of this design analysis is to specify and document the total and respirable fractions for radioactive materials that are released from an accident event at the Monitored Geologic Repository (MGR) involving commercial spent nuclear fuel (CSNF) in a dry environment. The total and respirable release fractions will be used to support the preclosure licensing basis for the MGR. The total release fraction is defined as the fraction of total CSNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. The radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses. This subset of the total release fraction is referred to as the respirable release fraction. Potential accidents may involve waste forms that are characterized as either bare (unconfined) fuel assemblies or confined fuel assemblies. The confined CSNF assemblies at the MGR are contained in shipping casks, canisters, or disposal containers (waste packages). In contrast to the bare fuel assemblies, the container that confines the fuel assemblies has the potential of providing an additional barrier for diminishing the total release fraction should the fuel rod cladding breach during an accident. However, this analysis will not take credit for this additional bamer and will establish only the total release fractions for bare unconfined CSNF assemblies, which may however be

Fractionated radiosurgery for painful spinal metastases: DOSIS - a phase II trial

Directory of Open Access Journals (Sweden)

Guckenberger Matthias

2012-11-01

Full Text Available Abstract Background One third of all cancer patients will develop bone metastases and the vertebral column is involved in approximately 70% of these patients. Conventional radiotherapy with of 1–10 fractions and total doses of 8-30 Gy is the current standard for painful vertebral metastases; however, the median pain response is short with 3–6 months and local tumor control is limited with these rather low irradiation doses. Recent advances in radiotherapy technology – intensity modulated radiotherapy for generation of highly conformal dose distributions and image-guidance for precise treatment delivery – have made dose-escalated radiosurgery of spinal metastases possible and early results of pain and local tumor control are promising. The current study will investigate efficacy and safety of radiosurgery for painful vertebral metastases and three characteristics will distinguish this study. 1 A prognostic score for overall survival will be used for selection of patients with longer life expectancy to allow for analysis of long-term efficacy and safety. 2 Fractionated radiosurgery will be performed with the number of treatment fractions adjusted to either good (10 fractions or intermediate (5 fractions life expectancy. Fractionation will allow inclusion of tumors immediately abutting the spinal cord due to higher biological effective doses at the tumor - spinal cord interface compared to single fraction treatment. 3 Dose intensification will be performed in the involved parts of the vertebrae only, while uninvolved parts are treated with conventional doses using the simultaneous integrated boost concept. Methods / Design It is the study hypothesis that hypo-fractionated image-guided radiosurgery significantly improves pain relief compared to historic data of conventionally fractionated radiotherapy. Primary endpoint is pain response 3 months after radiosurgery, which is defined as pain reduction of ≥ 2 points at the treated

Analytical incorporation of fractionation effects in probabilistic treatment planning for intensity-modulated proton therapy.

Science.gov (United States)

Wahl, Niklas; Hennig, Philipp; Wieser, Hans-Peter; Bangert, Mark

2018-04-01

We show that it is possible to explicitly incorporate fractionation effects into closed-form probabilistic treatment plan analysis and optimization for intensity-modulated proton therapy with analytical probabilistic modeling (APM). We study the impact of different fractionation schemes on the dosimetric uncertainty induced by random and systematic sources of range and setup uncertainty for treatment plans that were optimized with and without consideration of the number of treatment fractions. The APM framework is capable of handling arbitrarily correlated uncertainty models including systematic and random errors in the context of fractionation. On this basis, we construct an analytical dose variance computation pipeline that explicitly considers the number of treatment fractions for uncertainty quantitation and minimization during treatment planning. We evaluate the variance computation model in comparison to random sampling of 100 treatments for conventional and probabilistic treatment plans under different fractionation schemes (1, 5, 30 fractions) for an intracranial, a paraspinal and a prostate case. The impact of neglecting the fractionation scheme during treatment planning is investigated by applying treatment plans that were generated with probabilistic optimization for 1 fraction in a higher number of fractions and comparing them to the probabilistic plans optimized under explicit consideration of the number of fractions. APM enables the construction of an analytical variance computation model for dose uncertainty considering fractionation at negligible computational overhead. It is computationally feasible (a) to simultaneously perform a robustness analysis for all possible fraction numbers and (b) to perform a probabilistic treatment plan optimization for a specific fraction number. The incorporation of fractionation assumptions for robustness analysis exposes a dose to uncertainty trade-off, i.e., the dose in the organs at risk is increased for a

Adjuvant single-fraction radiotherapy is safe and effective for intractable keloids

International Nuclear Information System (INIS)

Song, Changhoon; Wu, Honggyun; Chang, Hak; Kim, Il Han; Ha, Sung W.

2014-01-01

The aim of this study was to assess the feasibility and efficacy of high-dose, single-fraction electron beam radiotherapy for therapy-resistant keloids. Before 2010, intractable keloids were treated at our institution with post-operative irradiation of 6-15 Gy in 3-5 fractionations. For convenience and cost effectiveness, we have changed our treatment protocol to high-dose single-fraction radiotherapy. A total of 12 patients with 16 keloid lesions were treated from January 2010 to January 2013 in our department. A 10-Gy dose of electron irradiation was given within 72 h of the surgical excision. The mean follow-up period was 20 months. Treatments were well tolerated, and there was no recurrence in any of the patients. Severe adverse effects were not observed. Surgical excision of the keloid, followed by immediate, single-fraction, high-dose radiotherapy, is both safe and effective in preventing recurrence of therapy-resistant keloids. (author)

Thyroid tumours following fractionated irradiation in childhood

International Nuclear Information System (INIS)

Vathaire, F. de; Grimaud, E.; Diallo, I.; Shamsaldin, A.

1997-01-01

Results of a cohort study designed to evaluate the long term risk of thyroid tumours after fractioned high doses of external beam radiotherapy received by the thyroid are reported. In this cohort study, doses have been estimated for each child. (author)

SU-F-J-68: Deformable Dose Accumulation for Voxel-Based Dose Tracking of PTV Cold Spots for Adaptive Radiotherapy of the Head and Neck

Energy Technology Data Exchange (ETDEWEB)

Liu, C; Chetty, I; Mao, W; Kumarasiri, A; Zhong, H; Brown, S; Siddiqui, F [Henry Ford Health System, Detroit, MI (United States)

2016-06-15

Purpose: To utilize deformable dose accumulation (DDA) to determine how cold spots within the PTV change over the course of fractionated head and neck (H&N) radiotherapy. Methods: Voxel-based dose was tracked using a DDA platform. The DDA process consisted of B-spline-based deformable image registration (DIR) and dose accumulation between planning CT’s and daily cone-beam CT’s for 10 H&N cancer patients. Cold spots within the PTV (regions receiving less than the prescription, 70 Gy) were contoured on the cumulative dose distribution. These cold spots were mapped to each fraction, starting from the first fraction to determine how they changed. Spatial correlation between cold spot regions over each fraction, relative to the last fraction, was computed using the Jaccard index Jk (Mk,N), where N is the cold spot within the PTV at the end of the treatment, and Mk the same region for fraction k. Results: Figure 1 shows good spatial correlation between cold spots, and highlights expansion of the cold spot region over the course of treatment, as a result of setup uncertainties, and anatomical changes. Figure 2 shows a plot of Jk versus fraction number k averaged over 10 patients. This confirms the good spatial correlation between cold spots over the course of treatment. On average, Jk reaches ∼90% at fraction 22, suggesting that possible intervention (e.g. reoptimization) may mitigate the cold spot region. The cold spot, D99, averaged over 10 patients corresponded to a dose of ∼65 Gy, relative to the prescription dose of 70 Gy. Conclusion: DDA-based tracking provides spatial dose information, which can be used to monitor dose in different regions of the treatment plan, thereby enabling appropriate mid-treatment interventions. This work is supported in part by Varian Medical Systems, Palo Alto, CA.

The effect of fractionated irradiation on cell kinetics

International Nuclear Information System (INIS)

Laasonen, A.; Pyrhoenen, S.; Kouri, M.; Raety, J.; Holsti, L.R.

1991-01-01

The effects of single and split-dose irradiation were compared by in vitro experiments on HeLa cells. Changes in rate of cell proliferation were detected by flow cytometry, simultaneously determining the DNA content and the bromodeoxyuridine incorporation of individual cells. Cell cultures were irradiated with either a single dose of 1-6 Gy or with a corresponding dose divided into multiple fractions given at 1-6-h intervals. A dose-dependent accumulation of cells in G2/M phase was observed. The method was sensitive enough for the detection of G2/M block even after 1 Gy. The block disappeared completely within a 24-h follow-up time at dose levels up to 3 Gy. Interestingly, no differences in cell kinetics were observed between the single and split-dose regiments. This approach proves to be valuable in evaluating novel fractionation models and the effects of radiation on the cell kinetics of human tumor cells. (orig.)

SU-G-BRA-12: Development of An Intra-Fractional Motion Tracking and Dose Reconstruction System for Adaptive Stereotactic Body Radiation Therapy in High-Risk Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Rezaeian, N Hassan; Chi, Y; Tian, Z; Jiang, S; Hannan, R; Jia, X [UT Southwestern Medical Center, Dallas, TX (United States)

2016-06-15

Purpose: A clinical trial on stereotactic body radiation therapy (SBRT) for high-risk prostate cancer is undergoing at our institution. In addition to escalating dose to the prostate, we have increased dose to intra-prostatic lesions. Intra-fractional prostate motion deteriorates well planned radiation dose, especially for the small intra-prostatic lesions. To solve this problem, we have developed a motion tracking and 4D dose-reconstruction system to facilitate adaptive re-planning. Methods: Patients in the clinical trial were treated with VMAT using four arcs and 10 FFF beam. KV triggered x-ray projections were taken every 3 sec during delivery to acquire 2D projections of 3D anatomy at the direction orthogonal to the therapeutic beam. Each patient had three implanted prostate markers. Our developed system first determined 2D projection locations of these markers and then 3D prostate translation and rotation via 2D/3D registration of the markers. Using delivery log files, our GPU-based Monte Carlo tool (goMC) reconstructed dose corresponding to each triggered image. The calculated 4D dose distributions were further aggregated to yield the delivered dose. Results: We first tested each module in our system. MC dose engine were commissioned to our treatment planning system with dose difference of <0.5%. For motion tracking, 1789 kV projections from 7 patients were acquired. The 2D marker location error was <1 mm. For 3D motion tracking, root mean square (RMS) errors along LR, AP, and CC directions were 0.26mm, 0.36mm, and 0.01mm respectively in simulation studies and 1.99mm, 1.37mm, and 0.22mm in phantom studies. We also tested the entire system workflow. Our system was able to reconstruct delivered dose. Conclusion: We have developed a functional intra-fractional motion tracking and 4D dose re-construction system to support our clinical trial on adaptive high-risk prostate cancer SBRT. Comprehensive evaluations have shown the capability and accuracy of our system.

A model of cardiovascular disease giving a plausible mechanism for the effect of fractionated low-dose ionizing radiation exposure.

Directory of Open Access Journals (Sweden)

Mark P Little

2009-10-01

Full Text Available Atherosclerosis is the main cause of coronary heart disease and stroke, the two major causes of death in developed society. There is emerging evidence of excess risk of cardiovascular disease at low radiation doses in various occupationally exposed groups receiving small daily radiation doses. Assuming that they are causal, the mechanisms for effects of chronic fractionated radiation exposures on cardiovascular disease are unclear. We outline a spatial reaction-diffusion model for atherosclerosis and perform stability analysis, based wherever possible on human data. We show that a predicted consequence of multiple small radiation doses is to cause mean chemo-attractant (MCP-1 concentration to increase linearly with cumulative dose. The main driver for the increase in MCP-1 is monocyte death, and consequent reduction in MCP-1 degradation. The radiation-induced risks predicted by the model are quantitatively consistent with those observed in a number of occupationally-exposed groups. The changes in equilibrium MCP-1 concentrations with low density lipoprotein cholesterol concentration are also consistent with experimental and epidemiologic data. This proposed mechanism would be experimentally testable. If true, it also has substantive implications for radiological protection, which at present does not take cardiovascular disease into account. The Japanese A-bomb survivor data implies that cardiovascular disease and cancer mortality contribute similarly to radiogenic risk. The major uncertainty in assessing the low-dose risk of cardiovascular disease is the shape of the dose response relationship, which is unclear in the Japanese data. The analysis of the present paper suggests that linear extrapolation would be appropriate for this endpoint.

Dose-rate effects in external beam radiotherapy redux

International Nuclear Information System (INIS)

Ling, C. Clifton; Gerweck, Leo E.; Zaider, Marco; Yorke, Ellen

2010-01-01

Recent developments in external beam radiotherapy, both in technical advances and in clinical approaches, have prompted renewed discussions on the potential influence of dose-rate on radio-response in certain treatment scenarios. We consider the multiple factors that influence the dose-rate effect, e.g. radical recombination, the kinetics of sublethal damage repair for tumors and normal tissues, the difference in α/β ratio for early and late reacting tissues, and perform a comprehensive literature review. Based on radiobiological considerations and the linear-quadratic (LQ) model we estimate the influence of overall treatment time on radio-response for specific clinical situations. As the influence of dose-rate applies to both the tumor and normal tissues, in oligo-fractionated treatment using large doses per fraction, the influence of delivery prolongation is likely important, with late reacting normal tissues being generally more sensitive to the dose-rate effect than tumors and early reacting tissues. In conventional fractionated treatment using 1.8-2 Gy per fraction and treatment times of 2-10 min, the influence of dose-rate is relatively small. Lastly, the dose-rate effect in external beam radiotherapy is governed by the overall beam-on-time, not by the average linac dose-rate, nor by the instantaneous dose-rate within individual linac pulses which could be as high as 3 x 10 6 MU/min.

Beam Attenuators and the Risk of Unrecognized Large-Fraction Irradiation of Critical Tissues

International Nuclear Information System (INIS)

Luka, S.; Marks, J.E.

2015-01-01

The use of radiation beam attenuators led to radiation injury of the spinal cord in one patient and of the peripheral nerve in another due to unsuspected large-fraction irradiation. The anatomic distribution of radiation dose was reconstructed in the sagittal plane for the patient who developed radiation myelopathy and in the axial plane for the patient who developed peripheral neuropathy. The actual dose delivered to the injured structure in each patient was taken from the dose distribution and recorded along with the time, number of fractions, and dose per fraction. The patient who developed radiation myelopathy received a total of 46.5 Gy in twenty-three 2.1 Gy fractions in 31 days to the upper cervical spinal cord where the thickness of the neck was less than the central axis thickness due to cervical lordosis and absence of a posterior compensating filter. The patient who developed peripheral neuropathy received 55 Gy in twenty-five 2.2 Gy fractions in 50 days to the femoral nerve using bolus over the groins and an anterior one-half value layer Cerrobend pelvic block to bias the dose anteriorly. Compensating filters and other beam attenuators should be used with caution because they may result in unsuspected large-fraction irradiation and total doses of radiation that exceed the tolerance of critical structures.

Beam Attenuators and the Risk of Unrecognized Large-Fraction Irradiation of Critical Tissues

Energy Technology Data Exchange (ETDEWEB)

Luka, S.; Marks, J.E.

2015-01-15

The use of radiation beam attenuators led to radiation injury of the spinal cord in one patient and of the peripheral nerve in another due to unsuspected large-fraction irradiation. The anatomic distribution of radiation dose was reconstructed in the sagittal plane for the patient who developed radiation myelopathy and in the axial plane for the patient who developed peripheral neuropathy. The actual dose delivered to the injured structure in each patient was taken from the dose distribution and recorded along with the time, number of fractions, and dose per fraction. The patient who developed radiation myelopathy received a total of 46.5 Gy in twenty-three 2.1 Gy fractions in 31 days to the upper cervical spinal cord where the thickness of the neck was less than the central axis thickness due to cervical lordosis and absence of a posterior compensating filter. The patient who developed peripheral neuropathy received 55 Gy in twenty-five 2.2 Gy fractions in 50 days to the femoral nerve using bolus over the groins and an anterior one-half value layer Cerrobend pelvic block to bias the dose anteriorly. Compensating filters and other beam attenuators should be used with caution because they may result in unsuspected large-fraction irradiation and total doses of radiation that exceed the tolerance of critical structures.

Four-Dimensional Patient Dose Reconstruction for Scanned Ion Beam Therapy of Moving Liver Tumors

International Nuclear Information System (INIS)

Richter, Daniel; Saito, Nami; Chaudhri, Naved; Härtig, Martin; Ellerbrock, Malte; Jäkel, Oliver; Combs, Stephanie E.; Habermehl, Daniel; Herfarth, Klaus; Durante, Marco; Bert, Christoph

2014-01-01

Purpose: Estimation of the actual delivered 4-dimensional (4D) dose in treatments of patients with mobile hepatocellular cancer with scanned carbon ion beam therapy. Methods and Materials: Six patients were treated with 4 fractions to a total relative biological effectiveness (RBE)–weighted dose of 40 Gy (RBE) using a single field. Respiratory motion was addressed by dedicated margins and abdominal compression (5 patients) or gating (1 patient). 4D treatment dose reconstructions based on the treatment records and the measured motion monitoring data were performed for the single-fraction dose and a total of 17 fractions. To assess the impact of uncertainties in the temporal correlation between motion trajectory and beam delivery sequence, 3 dose distributions for varying temporal correlation were calculated per fraction. For 3 patients, the total treatment dose was formed from the fractional distributions using all possible combinations. Clinical target volume (CTV) coverage was analyzed using the volumes receiving at least 95% (V 95 ) and 107% (V 107 ) of the planned doses. Results: 4D dose reconstruction based on daily measured data is possible in a clinical setting. V 95 and V 107 values for the single fractions ranged between 72% and 100%, and 0% and 32%, respectively. The estimated total treatment dose to the CTV exhibited improved and more robust dose coverage (mean V 95 > 87%, SD < 3%) and overdose (mean V 107 < 4%, SD < 3%) with respect to the single-fraction dose for all analyzed patients. Conclusions: A considerable impact of interplay effects on the single-fraction CTV dose was found for most of the analyzed patients. However, due to the fractionated treatment, dose heterogeneities were substantially reduced for the total treatment dose. 4D treatment dose reconstruction for scanned ion beam therapy is technically feasible and may evolve into a valuable tool for dose assessment

The response of mouse skin to multiple small doses of radiation

International Nuclear Information System (INIS)

Denekamp, J.; Harris, S.R.

1975-01-01

The response of mouse skin has been tested by irradiating the foot of albino mice and scoring erythema and desquamation during the following month. Multiple small doses of 150, 250 and 350 rad have been given 'daily', and the test dose necessary to achieve a given reaction has been determined one day after the last small fraction. This test dose has been compared with the single dose necessary to produce the same reaction level in previously untreated mice, in order to determine the ratio of the slopes of the dose-response curve at low and high doses: Slope ratio = (single dose - test dose)/total fractionated priming dose. In three separate experiments the slope ratio decreased as the dose per fraction was reduced from 350 to 150 rad. This conflicts with the data of Dutreix et al, who found a constant slope ratio over this dose range. The present data are compared with those obtained by Denekamp using 4, 9 and 14 fractions of 300 rad and by Douglas et al, using the same experimental technique, over the dose range 45 to 200 rad/fraction. In addition, the results from multifraction experiments in which equal dose increments were administered until the requisite skin reaction was achieved are also analysed in terms of their slope ratio (Fowler et al. Douglas et al). When all these results are plotted it is impossible to be sure whether the slope ratio is decreasing over the range 300 to 45 rad per fraction, although it seems likely. Most of the values at low doses lie in the range 0.15 to 0.25, indicating that at low doses the radiation is only 15 to 25% as effective per rad in causing cell death as at higher doses. (author)

Treating locally advanced lung cancer with a 1.5T MR-Linac - Effects of the magnetic field and irradiation geometry on conventionally fractionated and isotoxic dose-escalated radiotherapy.

Science.gov (United States)

Bainbridge, Hannah E; Menten, Martin J; Fast, Martin F; Nill, Simeon; Oelfke, Uwe; McDonald, Fiona

2017-11-01

This study investigates the feasibility and potential benefits of radiotherapy with a 1.5T MR-Linac for locally advanced non-small cell lung cancer (LA NSCLC) patients. Ten patients with LA NSCLC were retrospectively re-planned six times: three treatment plans were created according to a protocol for conventionally fractionated radiotherapy and three treatment plans following guidelines for isotoxic target dose escalation. In each case, two plans were designed for the MR-Linac, either with standard (∼7mm) or reduced (∼3mm) planning target volume (PTV) margins, while one conventional linac plan was created with standard margins. Treatment plan quality was evaluated using dose-volume metrics or by quantifying dose escalation potential. All generated treatment plans fulfilled their respective planning constraints. For conventionally fractionated treatments, MR-Linac plans with standard margins had slightly increased skin dose when compared to conventional linac plans. Using reduced margins alleviated this issue and decreased exposure of several other organs-at-risk (OAR). Reduced margins also enabled increased isotoxic target dose escalation. It is feasible to generate treatment plans for LA NSCLC patients on a 1.5T MR-Linac. Margin reduction, facilitated by an envisioned MRI-guided workflow, enables increased OAR sparing and isotoxic target dose escalation for the respective treatment approaches. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Gamma dose rates to body organs from immersion in a semi-infinite radioactive cloud; an alternate approach using absorbed fraction data for internal radionuclides

International Nuclear Information System (INIS)

Gillespie, F.C.

1982-01-01

This note shows that reasonable estimates of absorbed γ-dose rates for specific organs arising from whole body immersion in semi-infinite radioactive clouds may be obtained very simply from well known data on absorbed fractions for mono-energetic γ-sources uniformly distributed in the whole body. (author)

Comparison of single, fractionated and hyperfractionated irradiation on the development of normal tissue damage in rat lung

International Nuclear Information System (INIS)

Giri, P.G.S.; Kimler, B.F.; Giri, U.P.; Cox, G.G.; Reddy, E.K.

1985-01-01

The effect of fractionated thoracic irradiation on the development of normal tissue damage in rats was compared to that produced by single doses. Animals received a single dose of 15 Gy, 30 Gy in 10 daily fractions of 3 Gy each (fractionation), or 30 Gy in 30 fractions of 1 Gy each 3 times a day (hyperfractionation). The treatments produced minimal lethality since a total of only 6 animals died between days 273 and 475 after the initiation of treatment, with no difference in survival observed between the control and any of the 3 treated groups. Despite the lack of lethality, evidence of lung damage was obtained by histological examination. Animals that had received either single doses or fractionated doses had more of the pulmonary parenchyma involved than did animals that had received hyperfractionated doses. The authors conclude that, in the rat lung model, a total radiation dose of 30 Gy fractionated over 14 days produces no more lethality nor damage to lung tissue than does 15 Gy delivered as a single dose. However, long-term effects as evidenced by deposits of collagen and development of fibrosis are significantly reduced by hyperfractionation when compared to single doses and daily fractionation

Dose and Fractionation in Radiation Therapy of Curative Intent for Non-Small Cell Lung Cancer: Meta-Analysis of Randomized Trials

Energy Technology Data Exchange (ETDEWEB)

Ramroth, Johanna; Cutter, David J.; Darby, Sarah C. [Nuffield Department of Population Health, University of Oxford, Oxford, Oxfordshire (United Kingdom); Higgins, Geoff S. [Department of Oncology, University of Oxford, Oxford, Oxfordshire (United Kingdom); McGale, Paul [Nuffield Department of Population Health, University of Oxford, Oxford, Oxfordshire (United Kingdom); Partridge, Mike [CRUK/MRC Oxford Institute for Radiation Oncology, Oxford, Oxfordshire (United Kingdom); Taylor, Carolyn W., E-mail: carolyn.taylor@ndph.ox.ac.uk [Nuffield Department of Population Health, University of Oxford, Oxford, Oxfordshire (United Kingdom)

2016-11-15

Purpose: The optimum dose and fractionation in radiation therapy of curative intent for non-small cell lung cancer remains uncertain. We undertook a published data meta-analysis of randomized trials to examine whether radiation therapy regimens with higher time-corrected biologically equivalent doses resulted in longer survival, either when given alone or when given with chemotherapy. Methods and Materials: Eligible studies were randomized comparisons of 2 or more radiation therapy regimens, with other treatments identical. Median survival ratios were calculated for each comparison and pooled. Results: 3795 patients in 25 randomized comparisons of radiation therapy dose were studied. The median survival ratio, higher versus lower corrected dose, was 1.13 (95% confidence interval [CI] 1.04-1.22) when radiation therapy was given alone and 0.83 (95% CI 0.71-0.97) when it was given with concurrent chemotherapy (P for difference=.001). In comparisons of radiation therapy given alone, the survival benefit increased with increasing dose difference between randomized treatment arms (P for trend=.004). The benefit increased with increasing dose in the lower-dose arm (P for trend=.01) without reaching a level beyond which no further survival benefit was achieved. The survival benefit did not differ significantly between randomized comparisons where the higher-dose arm was hyperfractionated and those where it was not. There was heterogeneity in the median survival ratio by geographic region (P<.001), average age at randomization (P<.001), and year trial started (P for trend=.004), but not for proportion of patients with squamous cell carcinoma (P=.2). Conclusions: In trials with concurrent chemotherapy, higher radiation therapy doses resulted in poorer survival, possibly caused, at least in part, by high levels of toxicity. Where radiation therapy was given without chemotherapy, progressively higher radiation therapy doses resulted in progressively longer survival, and no

Dose and Fractionation in Radiation Therapy of Curative Intent for Non-Small Cell Lung Cancer: Meta-Analysis of Randomized Trials

International Nuclear Information System (INIS)

Ramroth, Johanna; Cutter, David J.; Darby, Sarah C.; Higgins, Geoff S.; McGale, Paul; Partridge, Mike; Taylor, Carolyn W.

2016-01-01

Purpose: The optimum dose and fractionation in radiation therapy of curative intent for non-small cell lung cancer remains uncertain. We undertook a published data meta-analysis of randomized trials to examine whether radiation therapy regimens with higher time-corrected biologically equivalent doses resulted in longer survival, either when given alone or when given with chemotherapy. Methods and Materials: Eligible studies were randomized comparisons of 2 or more radiation therapy regimens, with other treatments identical. Median survival ratios were calculated for each comparison and pooled. Results: 3795 patients in 25 randomized comparisons of radiation therapy dose were studied. The median survival ratio, higher versus lower corrected dose, was 1.13 (95% confidence interval [CI] 1.04-1.22) when radiation therapy was given alone and 0.83 (95% CI 0.71-0.97) when it was given with concurrent chemotherapy (P for difference=.001). In comparisons of radiation therapy given alone, the survival benefit increased with increasing dose difference between randomized treatment arms (P for trend=.004). The benefit increased with increasing dose in the lower-dose arm (P for trend=.01) without reaching a level beyond which no further survival benefit was achieved. The survival benefit did not differ significantly between randomized comparisons where the higher-dose arm was hyperfractionated and those where it was not. There was heterogeneity in the median survival ratio by geographic region (P<.001), average age at randomization (P<.001), and year trial started (P for trend=.004), but not for proportion of patients with squamous cell carcinoma (P=.2). Conclusions: In trials with concurrent chemotherapy, higher radiation therapy doses resulted in poorer survival, possibly caused, at least in part, by high levels of toxicity. Where radiation therapy was given without chemotherapy, progressively higher radiation therapy doses resulted in progressively longer survival, and no

Apoptotic potential and cell sensitivity to fractionated radiotherapy

International Nuclear Information System (INIS)

Rupnow, Brent A.; Murtha, Albert D.; Alarcon, Rodolfo M.; Giaccia, Amato J.; Knox, Susan J.

1997-01-01

Purpose/Objective: At present, the relationship between sensitivity to radiation-induced apoptosis and overall cellular radiosensitivity remains unclear. In particular, the relationship of apoptotic sensitivity to the survival of cells following fractionated irradiation has not been well studied. The purpose of the present study was to determine if increasing cell sensitivity to radiation-induced apoptosis would result in decreased clonogenic survival following single dose and fractionated irradiation in vitro. Materials and Methods: To address this, we chose a cell line (Rat-1MycER) in which the sensitivity to radiation-induced apoptosis could be altered by switching on or off the activity of a conditional c-Myc allele (c-MycER). The c-MycER construct expresses a full length c-Myc protein fused to a modified hormone binding domain of the estrogen receptor. Only in the presence of the estrogen analog 4-hydroxytamoxifen (4HT), does the conditional c-MycER become active. Apoptosis following irradiation in these cells (with and without c-MycER activation) was analyzed by flow cytometry to determine the percentage of cells undergoing apoptosis following various radiation doses and at different times after irradiation. Additionally, clonogenic survival analysis was performed following single radiation doses from 0 to 10 Gy and following five fractions of 2 or 4 Gy each. Survival of cells with and without c-MycER activation was compared. Furthermore, the effect of overexpressing the anti-apoptotic Bcl-2 gene on apoptosis induction and clonogenic survival of these cells was examined. Results: Rat-1MycER cells were strongly sensitized to radiation-induced apoptosis in a dose and time dependent manner when MycER was activated relative to cells treated without c-MycER activation. This c-Myc-mediated sensitivity to radiation-induced apoptosis was suppressed by overexpression of the anti-apoptotic protein Bcl-2. In addition to increasing apoptosis, activating c-MycER prior to

Comparison of Radiation-Induced Bystander Effect in QU-DB Cells after Acute and Fractionated Irradiation: An In Vitro Study.

Science.gov (United States)

Soleymanifard, Shokouhozaman; Bahreyni Toossi, Mohammad Taghi; Kamran Samani, Roghayeh; Mohebbi, Shokoufeh

2016-01-01

Radiation effects induced in non-irradiated cells are termed radiation-induced bystander effects (RIBE). The present study intends to examine the RIBE response of QU-DB bystander cells to first, second and third radiation fractions and compare their cumulative outcome with an equal, single acute dose. This experimental study irradiated three groups of target cells for one, two and three times with(60)Co gamma rays. One hour after irradiation, we transferred their culture media to non-irradiated (bystander) cells. We used the cytokinesis block micronucleus assay to evaluate RIBE response in the bystander cells. The numbers of micronuclei generated in bystander cells were determined. RIBE response to single acute doses increased up to 4 Gy, then decreased, and finally at the 8 Gy dose disappeared. The second and third fractions induced RIBE in bystander cells, except when RIBE reached to the maximum level at the first fraction. We split the 4 Gy acute dose into two fractions, which decreased the RIBE response. However, fractionation of 6 Gy (into two fractions of 3 Gy or three fractions of 2 Gy) had no effect on RIBE response. When we split the 8 Gy acute dose into two fractions we observed RIBE, which had disappeared following the single 8 Gy dose. The impact of dose fractionation on RIBE induced in QU-DB cells de- pended on the RIBE dose-response relationship. Where RIBE increased proportion- ally with the dose, fractionation reduced the RIBE response. In contrast, at high dos- es where RIBE decreased proportionally with the dose, fractionation either did not change RIBE (at 6 Gy) or increased it (at 8 Gy).

Radiation-induced hypopituitarism is dose-dependent

International Nuclear Information System (INIS)

Littley, M.D.; Shalet, S.M.; Beardwell, C.G.; Robinson, E.L.; Sutton, M.L.

1989-01-01

Radiation-induced hypopituitarism has been studies prospectively for up to 12 years in 251 adult patients treated for pituitary disease with external radiotherapy, ranging in dose from 20 Gy in eight fractions over 11 days to 45 Gy in 15 fractions over 21 days. Ten further patients were studied 2-4 years after whole-body irradiation for haematological malignancies using 12 Gy in six fractions over 3 days and seven patients were studied 3-11 years after whole-brain radiotherapy for a primary brain tumour (30 Gy, eight fractions, 11 days). Five years after treatment, patients who received 20 Gy had an incidence of TSH deficiency of 9% and in patients treated with 35-37 Gy, 40 Gy and 42-45 Gy, the incidence of TSH deficiency increased significantly with increasing dose. A similar relationship was observed for both ACTH and gonadotrophin deficiencies when the 20 Gy group was compared to patients treated with 35-45 Gy. Growth hormone deficiency was universal by 5 years over the dose range 35-45 Gy. In seven patients who were treated with 30 Gy in eight fractions over 11 days, deficiencies were observed at a similar frequency to the 40 Gy group (15 fractions, 21 days). No evidence of pituitary dysfunction was detected in the ten patients who received 12 Gy (six fractions, 3 days). (author)

Fractionated irradiation and haematopiesis. Pt. 2

International Nuclear Information System (INIS)

Ninkov, V.; Piletic, O.; Karanovic, D.; Belgrade Univ.

1980-01-01

Haemoregeneration after the irradiation with 600 R was studied using two different fractions given before and after the transplantation of bone-marrow cells. The dose of 600 R was divided in two uneven fractions: 500 + 100 R, 400 + 200 R and 300 + 300 R. During the free interval between the two doses (5 min) transplantation of bone-marrow cells was performed. Recolonization of bone-marrow and spleen was analysed on the 10th day after treatment. For analysis, samples of blood, bone-marrow and spleen were used. Maximal effect was found in the experimental group of animals irradiated with 500 R before and with 100 R after marrow-cell transplantation. Minimal haematopoietic response was in the group irradiated with 300 R before and after transplantation. This points at the importance of the primary dose for acceptance of the transplants and their activation. (orig.) [de

Studies of murine tumor control using x-ray fractionation schedules alone or in combination with hyperthermia

International Nuclear Information System (INIS)

Imbra, R.J.

1981-01-01

The effectiveness of an experimental radiation fractionation schedule of decreasing-sized dose fractions administered at optimal time intervals was compared with a conventional fractionation schedule of constant-sized dose fractions administered five times per week. Also, the effect of the addition of hyperthermia (42.5 0 C) to radiation therapy was investigated. For some experiments, Ehrlich mammary tumors were growth in the right thighs of Swiss mice. The tumor response was determined by measuring the tumor-bearing leg diameter and converting this value to volume. The time for the treated tumor to regrow to its pre-tratment volume was used as an endpoint in Swiss mice. The maximum total treatment dose is limited by the amount of normal tissue damage. A total treatment dose of six thousand rads was most suitable for the further investigations. Definitive investigations were performed using the RIF-1 tumor grown in the right thigh of C3H mice. The length of mitotic delay of RIF-1 cells, in vivo, was determined after various single doses of x radiation. A direct (exponential) relationship betwen x-ray dose and mitotic delay time was observed. Times of release of the RIF-1 cells from radiation-induced mitotic delay were used to determine the optimum time intervals to deliver the decreasing-sized dose fractions. Six thousand rads administered as decreasing-sized dose fractions resulted in significantly greater RIF-1 tumor control, as compared to conventional radiation therapy. The best treatment schedule, overall, was decreasing-sized dose fractions plus hyperthermia

High-Dose-Rate Brachytherapy of a Single Implant With Two Fractions Combined With External Beam Radiotherapy for Hormone-Naive Prostate Cancer

International Nuclear Information System (INIS)

Sato, Morio; Mori, Takashi; Shirai, Shintaro; Kishi, Kazushi; Inagaki, Takeshi; Hara, Isao

2008-01-01

Purpose: To evaluate the preliminary outcomes of high-dose-rate (HDR) brachytherapy of a single implant with two fractions and external beam radiotherapy (EBRT) for hormone-naive prostate cancer. Methods and Materials: Between March 2000 and Sept 2003, a total of 53 patients with tumor Stage T1c-T3b N0 M0 prostate cancer were treated with HDR brachytherapy boost doses (7.5 Gy/fraction) and 50-Gy EBRT during a 5.5-week period. Median follow-up was 61 months. Patients were divided into groups with localized (T1c-T2b) and advanced disease (T3a-T3b). We used the American Society for Therapeutic Radiology and Oncology (ASTRO) definition for biochemical failure. According to recommendations of the Radiation Therapy Oncology Group-ASTRO Phoenix Consensus Conference, biochemical failure-free control rates (BF-FCRs) at 3 years were investigated as 2 years short of the median follow-up. Results: Between April 2000 and Sept 2007, Common Terminology Criteria for Adverse Events Version 2.0 late Grade 2 genitourinary and gastrointestinal toxicity rates were 0% and 3.8%, respectively. Erectile preservation was 25% at 5 years. Overall survival was 88.1% and cause-specific survival was 100%. At 3 years, ASTRO BF-FCRs of the localized and advanced groups were 100% and 42%, respectively (p = 0.001). Conclusions: The HDR brachytherapy of a single implant with two fractions plus EBRT is effective in treating patients with localized hormone-naive prostate cancer, with the least genitourinary and gastrointestinal toxicities; however, longer median BF-FCR follow-up is required to assess these findings

Commercial SNF Accident Release Fractions

Energy Technology Data Exchange (ETDEWEB)

J. Schulz

2004-11-05

The purpose of this analysis is to specify and document the total and respirable fractions for radioactive materials that could be potentially released from an accident at the repository involving commercial spent nuclear fuel (SNF) in a dry environment. The total and respirable release fractions are used to support the preclosure licensing basis for the repository. The total release fraction is defined as the fraction of total commercial SNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. Radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses; this subset of the total release fraction is referred to as the respirable release fraction. Accidents may involve waste forms characterized as: (1) bare unconfined intact fuel assemblies, (2) confined intact fuel assemblies, or (3) canistered failed commercial SNF. Confined intact commercial SNF assemblies at the repository are contained in shipping casks, canisters, or waste packages. Four categories of failed commercial SNF are identified: (1) mechanically and cladding-penetration damaged commercial SNF, (2) consolidated/reconstituted assemblies, (3) fuel rods, pieces, and debris, and (4) nonfuel components. It is assumed that failed commercial SNF is placed into waste packages with a mesh screen at each end (CRWMS M&O 1999). In contrast to bare unconfined fuel assemblies, the

Commercial SNF Accident Release Fractions

International Nuclear Information System (INIS)

Schulz, J.

2004-01-01

The purpose of this analysis is to specify and document the total and respirable fractions for radioactive materials that could be potentially released from an accident at the repository involving commercial spent nuclear fuel (SNF) in a dry environment. The total and respirable release fractions are used to support the preclosure licensing basis for the repository. The total release fraction is defined as the fraction of total commercial SNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. Radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses; this subset of the total release fraction is referred to as the respirable release fraction. Accidents may involve waste forms characterized as: (1) bare unconfined intact fuel assemblies, (2) confined intact fuel assemblies, or (3) canistered failed commercial SNF. Confined intact commercial SNF assemblies at the repository are contained in shipping casks, canisters, or waste packages. Four categories of failed commercial SNF are identified: (1) mechanically and cladding-penetration damaged commercial SNF, (2) consolidated/reconstituted assemblies, (3) fuel rods, pieces, and debris, and (4) nonfuel components. It is assumed that failed commercial SNF is placed into waste packages with a mesh screen at each end (CRWMS M andO 1999). In contrast to bare unconfined fuel assemblies, the

Biochemical and immunological responses to low doses of ionizing radiation

International Nuclear Information System (INIS)

Shabon, M.H.; Sayed, Z.S.; Mahdy, E.M.; El-Gawish, M.A.; Shosha, W.

2006-01-01

Malondialdehyde, lactate dehydrogenase, iron concentration, IL-6 and IL-1b concentration, hemoglobin content, red cells, white cells and platelet counts were determined in seventy-two male albino rats divided into two main groups. The first one was subdivided into 7 subgroups; control and 6 irradiated subgroups with 0.1, 0.2, 0.3, 0.5, 0.7 and 1 Gy single dose of gamma radiation. The other was subdivided into 4 subgroups irradiated with fractionated doses of gamma radiation; three groups were irradiated with 0.3, 0.7 and 1 Gy (0.1 Gy/day) and the last subgroup with 1 Gy (0.2 Gy/day). All animals were sacrificed after three days of the last irradiation dose. The results revealed that all biochemical parameters were increased in rats exposed to fractionated doses more than the single doses. Hematological parameters were decreased in rats exposed to single doses more than the fractionated ones. In conclusion, the data of this study highlights the stimulatory effect of low ionizing radiation doses (= 1 Gy), whether single or fractionated, on some biochemical and immunological parameters

45 Gy - tolerance dose spinal cord - dogma or the facts?

International Nuclear Information System (INIS)

Maciejewski, B.; Hliniak, A.; Danczak-Ginalska, Z.; Meder, M.; Skolyszewski, J.; Reinfuss, M.; Korzeniowski, S.; Peszynski, J.; Jassem, J.

1993-01-01

Dose of 45 Gy as a tolerance dose for spinal cord was questioned based on review of clinical data. Some data show that for conventional fractionation with the dose per fraction of less than 2.0 Gy spinal cord tolerance dose may arise up to 50-55 Gy. This was the base for round-table discussion and the importance of clinical and physical risk factors of postirradiation spinal cord injury was discussed and previous diseases of spinal cord, size of dose per fraction and length of irradiated spinal cord were pointed out as high risk factors. It was concluded that from clinical point of view there is no reason and on need to verify and to increase tolerance dose for spinal cord. (author)

The effect of small radiation doses on the rat spinal cord: the concept of partial tolerance

International Nuclear Information System (INIS)

Ang, K.K.; Van Der Kogel, A.J.; Van Der Schueren, E.

1983-01-01

To evaluate the tolerance of the rat spinal cord to small radiation doses per fraction, an increasing number of fractions is required for induction of paralysis. The assessment of doses of 1-2 Gy, as used in the clinic, would require that over 100 fractions be given. The validity of replacing part of a fractionated irradiation of the spinal cord by a single large dose has been tested. Fractionated irradiation doses with 18 MeV X rays were followed by a ''top-up'' dose of 15 Gy as a single treatment. This is the fraction size of a treatment with two irradiation doses leading to paralysis in 50% of the animals (ED 50). Fractionated treatments were carried out with 2, 5, 10 and 20 fractions followed by the top-up dose of 15 Gy. the isoeffect curve, as a function of the number of fractions, has the same slope as experiments performed without top-up dose. The results show that the quality and quantity of cellular repair is not modified when part of a multifractionated exposure is replaced by a larger top-dose. An important consequence of this finding is, that in treatments with unequal fraction sizes, the partial tolerances can simply be added. Since a top-up dose can replace a sizable number of irradiation treatments, its application will allow investigations of the extent of sublethal damage repair for fraction sizes as low as 1 Gy

Evaluation of the 'dose of the day' for IMRT prostate cancer patients derived from portal dose measurements and cone-beam CT

International Nuclear Information System (INIS)

Zijtveld, Mathilda van; Dirkx, Maarten; Breuers, Marcel; Kuipers, Ruud; Heijmen, Ben

2010-01-01

Purpose: High geometrical and dosimetrical accuracies are required for radiotherapy treatments where IMRT is applied in combination with narrow treatment margins in order to minimize dose delivery to normal tissues. As an overall check, we implemented a method for reconstruction of the actually delivered 3D dose distribution to the patient during a treatment fraction, i.e., the 'dose of the day'. In this article results on the clinical evaluation of this concept for a group of IMRT prostate cancer patients are presented. Materials and methods: The actual IMRT fluence maps delivered to a patient were derived from measured EPID-images acquired during treatment using a previously described iterative method. In addition, the patient geometry was obtained from in-room acquired cone-beam CT images. For dose calculation, a mapping of the Hounsfield Units from the planning CT was applied. With the fluence maps and the modified cone-beam CT the 'dose of the day' was calculated. The method was validated using phantom measurements and evaluated clinically for 10 prostate cancer patients in 4 or 5 fractions. Results: The phantom measurements showed that the delivered dose could be reconstructed within 3%/3 mm accuracy. For prostate cancer patients, the isocenter dose agreed within -0.4 ± 1.0% (1 SD) with the planned value, while for on average 98.1% of the pixels within the 50% isodose surface the actually delivered dose agreed within 3% or 3 mm with the planned dose. For most fractions, the dose coverage of the prostate volume was slightly deteriorated which was caused by small prostate rotations and small inaccuracies in fluence delivery. The dose that was delivered to the rectum remained within the constraints used during planning. However, for two patients a large degrading of the dose delivery was observed in two fractions. For one patient this was related to changes in rectum filling with respect to the planning CT and for the other to large intra-fraction motion during

Effect of temporal distribution of dose on oncogenic transformation

International Nuclear Information System (INIS)

Miller, R.C.; Brenner, D.J.; Geard, C.R.; Marino, S.A.; Hall, E.J.

1988-01-01

Risk estimates for neutron hazards are of considerable social and economic importance. Effectiveness per unit dose of X or γ rays (low-LET radiations) has been consistently observed to be dependent on the temporal distribution of dose. In a series of comparisons, 0.5 Gy of single or fractionated (five fractions in 8 h), neutrons of 0.23, 0.35, 0.45, 5.9, or 13.7 MeV were delivered to a synchronous C3H 10T1/2 cells. Transformation frequencies per surviving cell are shown. Cells exposed to one energy (5.9 MeV) show a significant enhancement at the 95% level due to fractionated exposures, and at the 85% confidence level the 0.35- and 0.45-MeV fractionated exposures additionally result in significantly greater transformation frequencies. The frequencies of surviving cells per dish between a single or fractionated exposure vary by less than 10%. In three of five pairwise comparisons, fractionated exposures result in statistically greater frequencies of transformants per dish, and are in complete agreement with the results when induction is expressed as transformants per surviving cell. However, after 0.23-MeV neutron irradiation, the single dose resulted in a greater incidence of transformed foci than the fractionated dose

Effects of fractionated stereotactic radiotherapy for primary hepatocellular carcinoma

International Nuclear Information System (INIS)

Choi, Byeong Ock; Jang, Hong Seok; Kang, Young Nam; Choi, Ihl Bhong; Kang, Ki Mun; Chai, Gyu Young; Lee, Sang Wook

2005-01-01

Reports on the outcome of curative radiotherapy for the primary hepatocellular carcinoma (HCC) are rarely encountered in the literature. In this study, we report our experience of a clinical trial where fractionated stereotactic radiotherapy (SRT) was used in treating a primary HCC. A retrospective analysis was performed on 20 patients who had been histologically diagnosed as HCC and treated by fractionated SRT. The long diameter of tumor measured by CT was 2 ∼ 6.5 cm (average: 3.8 cm). A single dose of radiation used in fractionated SRT was 5 or 10 Gy; each dose was prescribed based on the planning target volume and normalized to 85 ∼ 99% isocenter dose. Patients were treated 3 ∼ 5 times per week for 2 weeks, with each receiving a total dose of 50 Gy (the median dose: 50 Gy). The follow up period was 3 ∼ 55 months (the median follow up period: 23 months). The response rate was 60% (12 patients), with 4 patients showing complete response (20%), 8 patients showing partial response (40%), and 8 patients showing stable disease (40%). The 1-year and 2-year survival rates were 70.0% and 43.1%, respectively,and the median survival time was 20 months. The 1-year and 2-year disease free survival rates were 65% and 32.5%, respectively, and the median disease-free survival rate was 19 months. Some acute complications of the treatment were noted as follows: dyspepsia in 12 patients (60%), nausea/emesis in 8 patients (40%), and transient liver function impairment in 6 patients (30%). However, there was no treatment related death. The study indicates that fractionated SRT is a relatively safe and effective method for treating primary HCC. Thus, fractionated SRT may be suggested as a local treatment for HCC of small lesion and containing a single lesion, when the patients are inoperable or operation is refused by the patients. We thought that fractionated SRT is a challenging treatment modality for the HCC

SU-D-204-02: BED Consistent Extrapolation of Mean Dose Tolerances

Energy Technology Data Exchange (ETDEWEB)

Perko, Z; Bortfeld, T; Hong, T; Wolfgang, J; Unkelbach, J [Massachusetts General Hospital, Boston, MA (United States)

2016-06-15

Purpose: The safe use of radiotherapy requires the knowledge of tolerable organ doses. For experimental fractionation schemes (e.g. hypofractionation) these are typically extrapolated from traditional fractionation schedules using the Biologically Effective Dose (BED) model. This work demonstrates that using the mean dose in the standard BED equation may overestimate tolerances, potentially leading to unsafe treatments. Instead, extrapolation of mean dose tolerances should take the spatial dose distribution into account. Methods: A formula has been derived to extrapolate mean physical dose constraints such that they are mean BED equivalent. This formula constitutes a modified BED equation where the influence of the spatial dose distribution is summarized in a single parameter, the dose shape factor. To quantify effects we analyzed 14 liver cancer patients previously treated with proton therapy in 5 or 15 fractions, for whom also photon IMRT plans were available. Results: Our work has two main implications. First, in typical clinical plans the dose distribution can have significant effects. When mean dose tolerances are extrapolated from standard fractionation towards hypofractionation they can be overestimated by 10–15%. Second, the shape difference between photon and proton dose distributions can cause 30–40% differences in mean physical dose for plans having the same mean BED. The combined effect when extrapolating proton doses to mean BED equivalent photon doses in traditional 35 fraction regimens resulted in up to 7–8 Gy higher doses than when applying the standard BED formula. This can potentially lead to unsafe treatments (in 1 of the 14 analyzed plans the liver mean dose was above its 32 Gy tolerance). Conclusion: The shape effect should be accounted for to avoid unsafe overestimation of mean dose tolerances, particularly when estimating constraints for hypofractionated regimens. In addition, tolerances established for a given treatment modality cannot

Motion-encoded dose calculation through fluence/sinogram modification

International Nuclear Information System (INIS)

Lu, Weiguo; Olivera, Gustavo H.; Mackie, Thomas R.

2005-01-01

Conventional radiotherapy treatment planning systems rely on a static computed tomography (CT) image for planning and evaluation. Intra/inter-fraction patient motions may result in significant differences between the planned and the delivered dose. In this paper, we develop a method to incorporate the knowledge of intra/inter-fraction patient motion directly into the dose calculation. By decomposing the motion into a parallel (to beam direction) component and perpendicular (to beam direction) component, we show that the motion effects can be accounted for by simply modifying the fluence distribution (sinogram). After such modification, dose calculation is the same as those based on a static planning image. This method is superior to the 'dose-convolution' method because it is not based on 'shift invariant' assumption. Therefore, it deals with material heterogeneity and surface curvature very well. We test our method using extensive simulations, which include four phantoms, four motion patterns, and three plan beams. We compare our method with the 'dose-convolution' and the 'stochastic simulation' methods (gold standard). As for the homogeneous flat surface phantom, our method has similar accuracy as the 'dose-convolution' method. As for all other phantoms, our method outperforms the 'dose-convolution'. The maximum motion encoded dose calculation error using our method is within 4% of the gold standard. It is shown that a treatment planning system that is based on 'motion-encoded dose calculation' can incorporate random and systematic motion errors in a very simple fashion. Under this approximation, in principle, a planning target volume definition is not required, since it already accounts for the intra/inter-fraction motion variations and it automatically optimizes the cumulative dose rather than the single fraction dose

Favorable Preliminary Outcomes for Men With Low- and Intermediate-risk Prostate Cancer Treated With 19-Gy Single-fraction High-dose-rate Brachytherapy

Energy Technology Data Exchange (ETDEWEB)

Krauss, Daniel J., E-mail: dkrauss@beaumont.edu [Oakland University William Beaumont School of Medicine, Royal Oak, Michigan (United States); Ye, Hong [Oakland University William Beaumont School of Medicine, Royal Oak, Michigan (United States); Martinez, Alvaro A. [21st Century Oncology, Farmington Hills, Michigan (United States); Mitchell, Beth; Sebastian, Evelyn; Limbacher, Amy; Gustafson, Gary S. [Oakland University William Beaumont School of Medicine, Royal Oak, Michigan (United States)

2017-01-01

Purpose: To report the toxicity and preliminary clinical outcomes of a prospective trial evaluating 19-Gy, single-fraction high-dose-rate (HDR) brachytherapy for men with low- and intermediate-risk prostate cancer. Methods and Materials: A total of 63 patients were treated according to an institutional review board-approved prospective study of single-fraction HDR brachytherapy. Eligible patients had tumor stage ≤T2a, prostate-specific antigen level ≤15 ng/mL, and Gleason score ≤7. Patients with a prostate gland volume >50 cm{sup 3} and baseline American Urologic Association symptom score >12 were ineligible. Patients underwent transrectal ultrasound-guided transperineal implantation of the prostate, followed by single-fraction HDR brachytherapy. Treatment was delivered using {sup 192}Ir to a dose of 19 Gy prescribed to the prostate, with no additional margin applied. Results: Of the 63 patients, 58 had data available for analysis. Five patients had withdrawn consent during the follow-up period. The median follow-up period was 2.9 years (range 0.3-5.2). The median age was 61.4 years. The median gland volume at treatment was 34.8 cm{sup 3}. Of the 58 patients, 91% had T1 disease, 71% had Gleason score ≤6 (29% with Gleason score 7), and the median pretreatment prostate-specific antigen level was 5.1 ng/mL. The acute and chronic grade 2 genitourinary toxicity incidence was 12.1% and 10.3%, respectively. No grade 3 urinary toxicity occurred. No patients experienced acute rectal toxicity grade ≥2, and 2 experienced grade ≥2 chronic gastrointestinal toxicity. Three patients experienced biochemical failure, yielding a 3-year cumulative incidence estimate of 6.8%. Conclusions: Single-fraction HDR brachytherapy is well-tolerated, with favorable preliminary biochemical and clinical disease control rates.

Released fraction of polychlorinated biphenyls from soil-biosolid system using a leaching procedure and its comparison with bioavailable fraction determined by wheat plant uptake.

Science.gov (United States)

Jachero, Lourdes; Leiva, Claudio; Ahumada, Inés; Richter, Pablo

2017-11-01

The bioavailability of polychlorinated biphenyls (PCBs) in soils amended with biosolids was estimated using an aqueous leaching process of the compounds combined with rotating disk sorptive extraction (RDSE), and compared with bioavailability determined through of PCB absorption in wheat plants growing in the same soil-biosolid matrix. The matrices consisted of soil amended with biosolids at doses of 30, 90, and 200 Mg/ha, which increase concomitantly the organic matter content of the matrix. Considering that PCBs were natively absent in both the biosolids and soil used, the compounds were spiked in the biosolids and aged for 10 days. For each biosolid dose, the aqueous leaching profile was studied and equilibrium time was calculated to be 33 h. The leaching fractions determined by RDSE, considering total PCBs studied, were 12, 7, and 6% and the bioavailable fractions absorbed by the wheat root were found to be 0.5, 0.3, and 0.2% for 30, 90, and 200 Mg/ha doses, respectively. Both fractions leachable and bioavailable decrease with both increasing hydrophobicity of the compound (Kow) and increasing in the biosolid dose. It was found that both fractions (leaching and bioavailable) correlated according to the bivariate least squares regression, represented by a coefficient of correlation of 0.86. Therefore, the application of the chemical method involving a leaching procedure is an alternative to estimate the bioavailable fraction of PCBs in wheat plants in a simpler and in a shorter time.

Essential oil composition of different fractions of Piper guineense ...

African Journals Online (AJOL)

The oil fractions also showed variable contact toxicity on impregnated filter paper. All doses of the n-hexane fraction were very toxic to the test insect than the control, causing 100% mortality after five days of exposure. All the fractions produced a strong repellent activity against the test insect. These results suggest that P.

Equivalent uniform dose concept evaluated by theoretical dose volume histograms for thoracic irradiation.

Science.gov (United States)

Dumas, J L; Lorchel, F; Perrot, Y; Aletti, P; Noel, A; Wolf, D; Courvoisier, P; Bosset, J F

2007-03-01

The goal of our study was to quantify the limits of the EUD models for use in score functions in inverse planning software, and for clinical application. We focused on oesophagus cancer irradiation. Our evaluation was based on theoretical dose volume histograms (DVH), and we analyzed them using volumetric and linear quadratic EUD models, average and maximum dose concepts, the linear quadratic model and the differential area between each DVH. We evaluated our models using theoretical and more complex DVHs for the above regions of interest. We studied three types of DVH for the target volume: the first followed the ICRU dose homogeneity recommendations; the second was built out of the first requirements and the same average dose was built in for all cases; the third was truncated by a small dose hole. We also built theoretical DVHs for the organs at risk, in order to evaluate the limits of, and the ways to use both EUD(1) and EUD/LQ models, comparing them to the traditional ways of scoring a treatment plan. For each volume of interest we built theoretical treatment plans with differences in the fractionation. We concluded that both volumetric and linear quadratic EUDs should be used. Volumetric EUD(1) takes into account neither hot-cold spot compensation nor the differences in fractionation, but it is more sensitive to the increase of the irradiated volume. With linear quadratic EUD/LQ, a volumetric analysis of fractionation variation effort can be performed.

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

[Immune regulation activity and mechanism of Tibetan Kefir exopolysaccharide fractions].

Science.gov (United States)

Meng, Li; Zhang, Lanwei

2009-12-01

To investigate the effects and mechanism on immune regulation activity in mice of two Tibetan Kefir exoploysaccharides (EPS) with different molecular weight of 0.1 x 10(5) - 3 x 10(5) (fraction 1) and 1.8 x 10(3) (fraction 2). The immune regulation activity experiment was carried out in vitro based on the Functional Assessment Procedure and Test Methods of Health Food, which was issued by Ministry of Health of China. First, we treated mice subjects with EPS at doses of 40 mg/kg, 80 mg/kg, 120 mg/kg through ig. Then we detected the index of immune organs, the ability of antibody production (tested by HC50), activity of NK cell, delayed type hypersensitivity (DTH) and phagocytosis of macrophage in mice. Finally, we examined the expression of Erk protein in Macrophages by Western Blot assay. Fraction 1 could promote HC50, activity of NK cell and DTH in mice which low dose showed better. Fraction 2 could promote DTH, phagocytosis of macrophage which high dose showed better. The expression of Erk and COX-2 had the same trend with Phagocytic index. We verified the two fractions of Tibetan Kefir EPS could enhance immune functions in mice. Fraction 1 regulated immune function through NK cell and B cell while fraction 2 through macrophage cell and T cell. The effects to macrophage of Tibetan Kefir EPS in mice may realize through extra cellular signal-regulated kinase Erk pathway.

Dose to the stomach wall from injected /sup 99m/Tc pertechnetate

International Nuclear Information System (INIS)

Ford, M.R.; Deus, S.F.; Snyder, W.S.

1976-01-01

In estimating the radiation dose to the gastrointestinal tract (GIT) it has been assumed generally that the measured activity in the tract, i.e., in the walls, is present in the contents. This assumption has been necessary because absorbed fractions for photons were available only for the source in the contents. During the past year and a half, however, absorbed fractions, or specific absorbed fractions, have been estimated for photon emitters in the walls. In the work presented here new values are applied to estimate dose to the walls of the GIT from administration of /sup 99m/Tc pertechnetate. The dose to the stomach wall from photons is found to be less than the dose from nonpenetrating radiation, assuming complete absorption of energy. Thus, a correct estimation of average dose to the wall requires use of absorbed fractions of energy for electrons as well as for photons. The problem is discussed and values of absorbed fractions for electrons are given which are based on a uniform distribution of the activity. However, a final resolution of the problem will require further biological data on the fraction of activity in the wall and the fraction in the contents

Review of time-dose effects in radiation therapy

International Nuclear Information System (INIS)

Peschel, R.E.; Fischer, J.J.

1980-01-01

A historical review of conventional fractionation offers little confidence that such treatment is optimal for all tumors. Thus manipulation of time-dose schedules may provide a relatively inexpensive yet potentially useful technique for improving therapeutic results in radiation therapy. Consideration of basic radiobiological principles and animal model data illustrates the complex and heterogeneous nature of normal tissue and tumor response to time-dose effects and supports the hypothesis that better time-dose prescriptions can be found in clinical practice. The number of possible time-dose prescriptions is very large, and a review of the clinical trials using nonconventional fractionation demonstrates that the sampled portion of the total three-dimensional space of time, fraction number, and dose has been very small. Only carefully designed clinical trials can establish the therapeutic advantage of a new treatment schedule, and methods for selecting the most promising schedules are discussed. The use of simple data reduction formulas for time-dose effects should be discarded since they ignore the very complexity and heterogeneity of tissues and tumors which may form the basis of improved clinical results

Radiobiological restrictions and tolerance doses of repeated single-fraction hdr-irradiation of intersecting small liver volumes for recurrent hepatic metastases

Directory of Open Access Journals (Sweden)

Wust Peter

2010-05-01

Full Text Available Abstract Background To assess radiobiological restrictions and tolerance doses as well as other toxic effects derived from repeated applications of single-fraction high dose rate irradiation of small liver volumes in clinical practice. Methods Twenty patients with liver metastases were treated repeatedly (2 - 4 times at identical or intersecting locations by CT-guided interstitial brachytherapy with varying time intervals. Magnetic resonance imaging using the hepatocyte selective contrast media Gd-BOPTA was performed before and after treatment to determine the volume of hepatocyte function loss (called pseudolesion, and the last acquired MRI data set was merged with the dose distributions of all administered brachytherapies. We calculated the BED (biologically equivalent dose for a single dose d = 2 Gy for different α/β values (2, 3, 10, 20, 100 based on the linear-quadratic model and estimated the tolerance dose for liver parenchyma D90 as the BED exposing 90% of the pseudolesion in MRI. Results The tolerance doses D90 after repeated brachytherapy sessions were found between 22 - 24 Gy and proved only slightly dependent on α/β in the clinically relevant range of α/β = 2 - 10 Gy. Variance analysis showed a significant dependency of D90 with respect to the intervals between the first irradiation and the MRI control (p 90 and the pseudolesion's volume. No symptoms of liver dysfunction or other toxic effects such as abscess formation occurred during the follow-up time, neither acute nor on the long-term. Conclusions Inactivation of liver parenchyma occurs at a BED of approx. 22 - 24 Gy corresponding to a single dose of ~10 Gy (α/β ~ 5 Gy. This tolerance dose is consistent with the large potential to treat oligotopic and/or recurrent liver metastases by CT-guided HDR brachytherapy without radiation-induced liver disease (RILD. Repeated small volume irradiation may be applied safely within the limits of this study.

Alternatives to dose, quality factor and dose equivalent for low level irradiation

International Nuclear Information System (INIS)

Sondhaus, C.A.; Bond, V.P.; Feinendegen, L.E.

1988-01-01

Randomly occurring energy deposition events produced by low levels of ionizing radiation interacting with tissue deliver variable amounts of energy to the sensitive target volumes within a small fraction of the cell population. A model is described in which an experimentally derived function relating event size to cell response probability operates mathematically on the microdosimetric event size distribution characterizing a given irradiation and thus determines the total fractional number of responding cells; this fraction measures the effectiveness of the given radiation. Normalizing to equal numbers of events produced by different radiations and applying this cell response or hit size effectiveness function (HSEF) should define radiation quality, or relative effectiveness, on a more nearly absolute basis than do the absorbed dose and dose evaluation, which are confounded when applied to low level irradiations. Examples using both calculation and experimental data are presented. 15 refs., 18 figs

Simulation of respiratory motion during IMRT dose delivery

International Nuclear Information System (INIS)

Mohn, Silje; Wasboe, Ellen

2011-01-01

Background. When intensity modulated radiation therapy (IMRT) is realised with dynamic multi-leaf collimators (MLC) and given under respiratory motion, dosimetric errors may occur. These errors are a consequence of the dose blurring and the interplay between the organ motion and the leaf motion. In the present study, a model for evaluating these dosimetric effects for patient-specific cases has been developed and tested. Material and methods. In the purpose written software, three dimensional (3D) dose distributions can be calculated both with and without a generated breathing cycle. To validate the presented model and illustrate its application, periodic breathing cycles were generated, where the starting phase was set randomly for each field during the calculations. Respiration in the anterior-posterior (AP), superior-inferior (SI) and left-right (LR) direction was tested and verified. To illustrate the application of the presented model, two 5-fields IMRT plans with different complexity were calculated with a 2 cm peak-to-peak motion in the AP direction for one fraction and for 25 fractions. Results. The results showed that the calculation method is of good accuracy, in particular for IMRT plans consisting of several fields, where 97% of the pixels within the body fulfilled a tolerance set to 4% dose difference and 4 mm distance to agreement (DTA). For the two IMRT plans with different complexity, pronounced respiratory induced dose errors, which increased with increasing complexity, were found for both one fraction and 25 fractions, but due to the random stating phase the interplay effect was considerably reduced for the plans consisting of 25 fractions. This illustrates how the dosimetric effects will vary depending on the dose plan and on the number of fractions investigated. Conclusion. For patient specific cases, the model can with good accuracy calculate 3D dose distributions both with and without respiratory motion, and evaluate the dosimetric effects

Adapting IMRT delivery fraction-by-fraction to cater for variable intrafraction motion

International Nuclear Information System (INIS)

Webb, S

2008-01-01

This paper presents a technique for coping with variable intrafraction organ motion when delivering intensity-modulated radiation therapy (IMRT). The strategy is an adaptive delivery in which the fluence delivered up to a particular fraction is subtracted from the required total-course planned fluence to create an adapted residual fluence for the next fraction. This requires that the fluence already delivered can be computed, knowing the intrafraction motion during each fraction. If the adaptation is unconstrained, as would be required for perfect delivery of the planned fluence, then the individual fractional fluences would become unphysical, with both negative components and spikes. Hence it is argued that constraints must be applied; first, positivity constraints and second, constraints to limit fluence spikes. Additionally, it is shown to be helpful to constrain other quantities which are explained. The power of the strategy is that it adapts to the (potentially variable) moving geometry during each fraction. It is not a perfect delivery but it is always better than making no adaptation. The fractionated nature of radiation therapy is thus exploited to advantage. The fluence adaptation method does not require re-planning at each fraction but this imposes limitations which are stated. The fuller theory of dose adaptation is also developed for intrafraction motion. The method is complementary to other adaptive strategies recently discussed with respect to interfraction motion

Evaluation of uneven fractionation radiotherapy of cervical lymph node-metastases by linear quadratic model

International Nuclear Information System (INIS)

Sasaki, Takehito; Kamata, Rikisaburo; Urahashi, Shingo; Yamaguchi, Tetsuji.

1993-01-01

One hundred and sixty-nine cervical lymph node-metastases from head and neck squamous cell carcinomas treated with either even fractionation or uneven fractionation regimens were analyzed in the present investigation. Logistic multivariate regression analysis indicated that: type of fractionation (even vs uneven), size of metastases, T value of primary tumors, and total dose are independent variables out of 18 variables that significantly influenced the rate of tumor clearance. The data, with statistical bias corrected by the regression equation, indicated that the uneven fractionation scheme significantly improved the rate of tumor clearance for the same size of metastases, total dose, and overall time compared to the even fractionation scheme. Further analysis by a linear-quadratic cell survival model indicated that the clinical improvement by uneven fractionation might not be explained entirely by a larger dose per fraction. It is suggested that tumor cells irradiated with an uneven fractionation regimen might repopulate more slowly, or they might be either less hypoxic or redistributed in a more radiosensitive phase in the cell cycle than those irradiated with even fractionation. This conclusion is clearly not definite, but it is suitable, pending the results of further investigation. (author)

Estimation of dependence between mean of fractionation of photons and neutrons dose and intensity of post-irradiation reaction of mouse large intestine; Ocena zaleznosci pomiedzy sposobem frakcjonowania dawki fotonow i neutronow a nasileniem popromiennego odczynu jelita grubego myszy

Energy Technology Data Exchange (ETDEWEB)

Gasinska, A. [Oncology Center, Cracow (Poland)

1995-12-31

The aim of the work was verification of mouse large intestine tolerance on fractionated 250 kV X-rays and 2.3 MeV neutrons doses. Two cm of large intestine of mouse CBA/HT strain were irradiated with various fraction doses: from 0.25 to 35 Gy of X-rays and 0.05-12 Gy of neutrons. The measure of injury was handicap of intestine function. Early post-irradiation reaction was measured by loss of body weight (2-3 weeks after irradiation) and mouse mortality (till 2 months after irradiation, LD50/2). The late reaction was measured on the base of maximal body weight in 1 year period after irradiation, deformation of excrements (after 10 months) and death of animals (till 12. month after irradiation, LD50/12). Fractionation of X-ray dose influenced on decrease of intensification of late irradiation effects. After fractionation of neutrons this effect has not been observed. {alpha}/{beta} coefficient for X-rays was 19.9 Gy [15.2; 27.0] for body weight nadir, 13.4 Gy [9.3; 19.5] for early mortality (LD50/2), 6.4 Gy [3.6;11.0] for maximal body weight and 6.9 [4.2; 10.8] for late mortality (LD50/12). Analysis of influence of low doses of photons 90.25-4 Gy) and neutrons (0.05-0.8 Gy) showed trend to reduction {alpha}/{beta} for photons only (LD50/2=5.4 Gy; LD50/12=4.6 Gy). {alpha}/{beta} coefficient for neutrons was defined by LQ model only for maximal body weight and was 19.9 Gy [9.5; 61.0]. In application of graphic method {alpha}/{beta} for neutrons was 230 Gy for early and 48 Gy for late effects. Lower values of {alpha}/{beta} coefficient for late irradiation effects for photon radiation demonstrate the big influence of fractionation of photons dose on large intestine tolerance (decrease intensity in all biological effects). Author did not observe increase of intestine tolerance in fractionation of neutrons dose. Effect of irradiation damages repair in interfraction pauses, measured by percent of regenerated dose (F{sub r}) was much bigger for photons. For X-rays it was 50

SU-E-J-105: Stromal-Epithelial Responses to Fractionated Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Qayyum, M [Little Company of Mary Hospital, Ever Green Park, IL (United States)

2014-06-01

Purpose: The stromal-epithelial-cell interactions that are responsible for directing normal breast-tissue development and maintenance play a central role in the progression of breast cancer. In the present study, we developed three-dimensional (3-D) cell co-cultures used to study cancerous mammary cell responses to fractionated radiotherapy. In particular, we focused on the role of the reactive stroma in determining the therapeutic ratio for postsurgical treatment. Methods: Cancerous human mammary epithelial cells were cultured in a 3-D collagen matrix with human fibroblasts stimulated by various concentrations of transforming growth factor beta 1 (TGF-β1). These culture samples were designed to model the post-lumpectomy mammary stroma in the presence of residual cancer cells. We tracked over time the changes in medium stiffness, fibroblast-cell activation (conversion to cancer activated fibroblasts (CAF)), and proliferation of both cell types under a variety of fractionated radiotherapy protocols. Samples were exposed to 6 MV X-rays from a linear accelerator in daily fraction sizes of 90, 180 and 360 cGy over five days in a manner consistent with irradiation exposure during radiotherapy. Results: We found in fractionation studies with fibroblasts and CAF that higher doses per fraction may be more effective early on in deactivating cancer-harboring cellular environments. Higher-dose fraction schemes inhibit contractility in CAF and prevent differentiation of fibroblasts, thereby metabolically uncoupling tumor cells from their surrounding stroma. Yet, over a longer time period, the higher dose fractions may slow wound healing and increase ECM stiffening that could stimulate proliferation of surviving cancer cells. Conclusion: The findings suggest that dose escalation to the region with residual disease can deactivate the reactive stroma, thus minimizing the cancer promoting features of the cellular environment. Large-fraction irradiation may be used to sterilize

SU-E-J-105: Stromal-Epithelial Responses to Fractionated Radiotherapy

International Nuclear Information System (INIS)

Qayyum, M

2014-01-01

Purpose: The stromal-epithelial-cell interactions that are responsible for directing normal breast-tissue development and maintenance play a central role in the progression of breast cancer. In the present study, we developed three-dimensional (3-D) cell co-cultures used to study cancerous mammary cell responses to fractionated radiotherapy. In particular, we focused on the role of the reactive stroma in determining the therapeutic ratio for postsurgical treatment. Methods: Cancerous human mammary epithelial cells were cultured in a 3-D collagen matrix with human fibroblasts stimulated by various concentrations of transforming growth factor beta 1 (TGF-β1). These culture samples were designed to model the post-lumpectomy mammary stroma in the presence of residual cancer cells. We tracked over time the changes in medium stiffness, fibroblast-cell activation (conversion to cancer activated fibroblasts (CAF)), and proliferation of both cell types under a variety of fractionated radiotherapy protocols. Samples were exposed to 6 MV X-rays from a linear accelerator in daily fraction sizes of 90, 180 and 360 cGy over five days in a manner consistent with irradiation exposure during radiotherapy. Results: We found in fractionation studies with fibroblasts and CAF that higher doses per fraction may be more effective early on in deactivating cancer-harboring cellular environments. Higher-dose fraction schemes inhibit contractility in CAF and prevent differentiation of fibroblasts, thereby metabolically uncoupling tumor cells from their surrounding stroma. Yet, over a longer time period, the higher dose fractions may slow wound healing and increase ECM stiffening that could stimulate proliferation of surviving cancer cells. Conclusion: The findings suggest that dose escalation to the region with residual disease can deactivate the reactive stroma, thus minimizing the cancer promoting features of the cellular environment. Large-fraction irradiation may be used to sterilize

On the effect of small radiation doses: Desoxyribonucleic acid (DNA) synthesis and DNA repair of thymus, spleen, and bone marrow cells in the rat after fractionated total body X-ray irradiation. Zur Wirkung kleiner Strahlendosen: Desoxyribonukleinsaeure-(DNA-)Synthese und DNA-Reparatur von Thymus-, Milz- und Knochenmarkszellen der Ratte nach fraktionierter Ganzkoerperroentgenbestrahlung

Energy Technology Data Exchange (ETDEWEB)

Tempel, K.; Ehling, G. (Muenchen Univ. (Germany, F.R.). Inst. fuer Pharmakologie, Toxikologie und Pharmazie)

1989-09-01

After three to seven days following to fractionated total body X-ray irradiation (TBI) (four expositions with doses of 0.3 to 5.0 cGy per fraction at intervals of 24 hours), a maximum 50 percent stimulation of the semiconservative DNA synthesis (SDS) of spleen cells was measured in vitro. This was not dependent of the fact if an acute high-dose (400 and/or 800 cGy) unique irradiation was applied after the fractionated TBI at the moment of stimulation. A significant increase of {sup 3}H-thymidine incorporation into the DNA of bone marrow and thymus cells was only found when doses of 1.25 cGy per fraction had been used. After fractionated TBI with doses of {ge}5 cGy per fraction, an increase of DNA synthesis resistant to hydroxyurea ('unprogrammed' DNA synthesis, UDS) was demonstrated in spleen cells. The UV-simulated UDS decreased proportionately. The sedimentation of thymus, spleen, and bone marrow nucleoids in a neutral saccharose gradient gave no evidence of an increased DNA repair capacity after fractionated TBI. Whereas the SDS stimulation by fractionated TBI with small doses can be explained by a modified proliferation behavior of exposed cells, the UDS behavior of spleen cells after considerably higher radiation doses suggests regenerative processes correlated with an increased number of cells resistant to hydroxyurea and cells presenting an UV repair deficiency. These findings can be considered to be a further proof of the assumed immune-stimulating effect of small radiation doses. (orig.).

Intradermal Inactivated Poliovirus Vaccine: A Preclinical Dose-Finding Study

OpenAIRE

Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin

2014-01-01

Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial...

Damage to the surface of the small intestinal villus: an objective scale of assessment of the effects of single and fractionated radiation doses

Energy Technology Data Exchange (ETDEWEB)

Carr, K.E.; Watt, C. (Glasgow Univ. (UK). Dept. of Anatomy); Hamlet, R.; Nias, A.H.W. (Glasgow Inst. of Radiotherapeutics and Oncology (UK))

1983-07-01

Scanning electron microscopy has been used to compare damage to mouse small intestinal mucosa after irradiation with different doses of photons and neutrons. Various stages of the collapse of villous structure seen after radiation include the production of conical and rudimentary villi and a flattened mucosa. A scale is proposed to relate radiation to villous damage. Points from this scale are taken to produce comparative ratios for equivalent damage produced by different radiation conditions. RBE values are quoted for neutron, X and gamma radiation given as single or fractionated irradiation doses and as whole or partial body irradiation. The relationship between the stroma in intravillous pegs and that of the pericryptal compartment is explored.

Damage to the surface of the small intestinal villus: an objective scale of assessment of the effects of single and fractionated radiation doses

International Nuclear Information System (INIS)

Carr, K.E.; Watt, C.

1983-01-01

Scanning electron microscopy has been used to compare damage to mouse small intestinal mucosa after irradiation with different doses of photons and neutrons. Various stages of the collapse of villous structure seen after radiation include the production of conical and rudimentary villi and a flattened mucosa. A scale is proposed to relate radiation to villous damage. Points from this scale are taken to produce comparative ratios for equivalent damage produced by different radiation conditions. RBE values are quoted for neutron, X and gamma radiation given as single or fractionated irradiation doses and as whole or partial body irradiation. The relationship between the stroma in intravillous pegs and that of the pericryptal compartment is explored. (author)

The determination of the inhalable fraction of 40K activity in marijuana (Cannabis sativa L. buds by instrumental neutron activation analysis and the effective dose to the body

Directory of Open Access Journals (Sweden)

Johann M.R. Antoine

2017-07-01

Full Text Available Total potassium in marijuana (Cannabis sativa L. buds was determined using instrumental neutron activation analysis. The mass fraction of 40K and its activity were derived using the natural isotopic ratios of potassium. The total potassium in the marijuana buds ranged from 0.84% to 3.15% with a mean mass fraction of 1.93%. The activity concentrations of 40K in the samples of marijuana ranged from 253 to 946 Bq kg−1 with a mean activity concentration of 581 Bq kg−1. The effective dose to the body from smoking marijuana is lower than that for comparable tobacco smoking. Simulated smoking experiments show that over 90% of 40K is retained in the cigarette ash. Accepted methods of determining effective dose to the body from 40K inhalation are likely overestimations for both marijuana and tobacco cigarette smoke.

Effectiveness of perfluorochemical emulsions and carbogen breathing with fractionated irradiation

International Nuclear Information System (INIS)

Moulder, J.E.; Fish, B.L.

1987-01-01

Oxygen-carrying perfluorochemical emulsions have been shown to enhance the response of experimental tumors to large single doses of radiation. Clinically, however, perfluorochemical emulsions will be used with only some fractions of multiple fraction radiation courses. To test the efficacy of a perfluorochemical emulsion (Fluosol-DA 20%, supplied by Alpha Therapeutic Co) under these conditions, BA1112 rat sarcomas were treated with three fractions/week of 6.25 Gy/fraction. Once a week, animals were given Fluosol-DA at 15 ml/kg, and allowed to breathe 95% O/sub 2/:5% CO/sub 2/ (carbogen) for 30 min prior to and during irradiation. The tumor regression rate during treatment was significantly greater in the Fluosol arm than in the control arm. Preliminary data analysis shows a 50% tumor control dose of 86.0 Gy (95% cl:78.0 - 94.3 Gy) in the control arm compared to 69.1 Gy (95% cl:58.3 - 77.3 Gy) in the Fluosol arm. The dose modification factor for intermittent Fluosol and carbogen breathing is 1.26 (95% cl:1.08 - 1.50). In the same fractionated schedule 0.4 mg/kg misonidazole, given once per week, gave a sensitizer enhancement ratio of 1.15 (95% cl:1.03 - 1.33)

Role of Rad52 in fractionated irradiation induced signaling in A549 lung adenocarcinoma cells

International Nuclear Information System (INIS)

Ghosh, Somnath; Krishna, Malini

2012-01-01

The effect of fractionated doses of γ-irradiation (2 Gy per fraction over 5 days), as delivered in cancer radiotherapy, was compared with acute doses of 10 and 2 Gy, in A549 cells. A549 cells were found to be relatively more radioresistant if the 10 Gy dose was delivered as a fractionated regimen. Microarray analysis showed upregulation of DNA repair and cell cycle arrest genes in the cells exposed to fractionated irradiation. There was intense activation of DNA repair pathway-associated genes (DNA-PK, ATM, Rad52, MLH1 and BRCA1), efficient DNA repair and phospho-p53 was found to be translocated to the nucleus of A549 cells exposed to fractionated irradiation. MCF-7 cells responded differently in fractionated regimen. Silencing of the Rad52 gene in fractionated group of A549 cells made the cells radiosensitive. The above result indicated increased radioresistance in A549 cells due to the activation of Rad52 gene.

Immune responses after fractional doses of inactivated poliovirus vaccine using newly developed intradermal jet injectors: a randomized controlled trial in Cuba.

Science.gov (United States)

Resik, Sonia; Tejeda, Alina; Mach, Ondrej; Fonseca, Magile; Diaz, Manuel; Alemany, Nilda; Garcia, Gloria; Hung, Lai Heng; Martinez, Yenisleydis; Sutter, Roland

2015-01-03

The World Health Organization recommends that, as part of the new polio endgame, a dose of inactivated poliovirus vaccine (IPV) be introduced by the end of 2015 in all countries using only oral poliovirus vaccine (OPV). Administration of fractional dose (1/5th of full dose) IPV (fIPV) intradermally may reduce costs, but its administration is cumbersome with BCG needle and syringe. We evaluated performance of two newly developed intradermal-only jet injectors and compared the immune response induced by fIPV with that induced by full-dose IPV. Children between 12 and 20 months of age, who had previously received two doses of OPV, were enrolled in Camaguey, Cuba. Subjects received a single dose of IPV (either full-dose IPV intramuscularly with needle and syringe or fIPV intradermally administered with one of two new injectors or with BCG needle or a conventional needle-free injector). Serum was tested for presence of poliovirus neutralizing antibodies on day 0 (pre-IPV) and on days 3, 7 and 21 (post-vaccination). Complete data were available from 74.2% (728/981) subjects. Baseline median antibody titers were 713, 284, and 113 for poliovirus types 1, 2, and 3, respectively. Seroprevalence at study end were similar across the intervention groups (≥ 94.8%). The immune response induced with one new injector was similar to BCG needle and to the conventional injector; and superior to the other new injector. fIPV induced significantly lower boosting response compared to full-dose IPV. No safety concerns were identified. One of the two new injectors demonstrated its ability to streamline intradermal fIPV administration, however, further investigations are needed to assess the potential contribution of fIPV in the polio endgame plan. Copyright © 2014 Elsevier Ltd. All rights reserved.

High-dose-rate brachytherapy as monotherapy delivered in two fractions within one day for favorable/intermediate-risk prostate cancer: preliminary toxicity data.

Science.gov (United States)

Ghilezan, Michel; Martinez, Alvaro; Gustason, Gary; Krauss, Daniel; Antonucci, J Vito; Chen, Peter; Fontanesi, James; Wallace, Michelle; Ye, Hong; Casey, Alyse; Sebastian, Evelyn; Kim, Leonard; Limbacher, Amy

2012-07-01

To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy × 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy × 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of ≤12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. The median follow-up was 17 months (range, 6-40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. Favorable-risk prostate cancer patients treated with a single implant HDR-BT to 24-27 Gy in two fractions

High-Dose-Rate Brachytherapy as Monotherapy Delivered in Two Fractions Within One Day for Favorable/Intermediate-Risk Prostate Cancer: Preliminary Toxicity Data

Energy Technology Data Exchange (ETDEWEB)

Ghilezan, Michel, E-mail: mghilezan@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital and Rose Cancer Institute, Royal Oak, Michigan (United States); Martinez, Alvaro; Gustason, Gary; Krauss, Daniel; Antonucci, J. Vito; Chen, Peter; Fontanesi, James; Wallace, Michelle; Ye Hong; Casey, Alyse; Sebastian, Evelyn; Kim, Leonard; Limbacher, Amy [Department of Radiation Oncology, William Beaumont Hospital and Rose Cancer Institute, Royal Oak, Michigan (United States)

2012-07-01

Purpose: To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy Multiplication-Sign 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy Multiplication-Sign 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. Methods and Materials: A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of {<=}12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. Results: The median follow-up was 17 months (range, 6-40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. Conclusions: Favorable

High-Dose-Rate Brachytherapy as Monotherapy Delivered in Two Fractions Within One Day for Favorable/Intermediate-Risk Prostate Cancer: Preliminary Toxicity Data

International Nuclear Information System (INIS)

Ghilezan, Michel; Martinez, Alvaro; Gustason, Gary; Krauss, Daniel; Antonucci, J. Vito; Chen, Peter; Fontanesi, James; Wallace, Michelle; Ye Hong; Casey, Alyse; Sebastian, Evelyn; Kim, Leonard; Limbacher, Amy