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Results for “Dose Fractionation, Radiation”

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PubMedDate not supplied

An effective dose computation model for fractionated radiation dose.

A mathematical model of sensitivity change and cell proliferation for fractionated radiation effect is presented here in which cell proliferation is regarded as part of the virtual recovery of radiated tissues. The obtained values of parameters in this model were applied to reported fractionated radiation data. The values in normal and malignant tissues were not identical. The difference of the values accounts for the increased therapeutic ratio in fractionated radiation. A procedure to optimize fractionated radiation schemes is also presented.

Cell Division↗

PubMed1994

Effect of in utero radiation dose fractionation on rat postnatal development, behavior and brain structure: 3-hour interval.

Effect of In Utero Radiation Dose Fractionation on Rat Postnatal Development, Behavior and Brain Structure: 3-Hour Interval. Neurotoxicology 15(1): 183-190, 1994. We have previously shown that exposure of the rat fetus to ionizing radiation produces dose-dependent (0.25-1.25 Gy) changes in postnatal growth and behavior, and decreases in cerebral cortex thickness. Pregnant rats were exposed to single doses of 0.5 or 1.0 Gy, or to two doses of 0.5 Gy (separated by a 3 h interval) on gestational day 15. Pups were weighed and subjected to behavioral tests (righting reflex; reflex suspension; negative geotaxis; continuous corridor; and length, width, and sine of gait) over postnatal days 7-28. The rats were then sacrificed and brains removed for histology. The fractionated doses produced responses that were generally intermediate between those produced by the single doses and which, by interpolation, could be expressed as equivalent to a single dose between 0.5 and 1.0 Gy. Overall, exposure of the fetal rat to two doses of 0.5 Gy separated by 3 h produced effects equivalent to a single dose of 0.85 Gy. We conclude that fractionation of radiation dose results in less damage to the developing rat cerebral cortex, as measured by postnatal growth, behavioral tests, and morphological assessment.

Animals↗

PubMed1981

High-dose fractionated radiation therapy for select patients with brain metastases.

Four patients with metastases to the brain were treated by high-dose fractionated radiation therapy. In all four cases, a complete response and prolonged disease-free survival could be documented. Unlike the standard therapy for such patients (i.e., craniotomy and postoperative irradiation), high-dose fractionated radiation therapy carries no operative risk and can encompass multiple brain metastases and metastases in deep or critical intracranial sites.

Adult↗

PubMed2000

How do waiting times affect radiation dose fractionation schedules?

The purpose of the present paper was to evaluate the changing patterns of dose prescription at the Queensland Radium Institute from 1995 to 1998 inclusive. Data were analysed from the treatment files collected on each patient and these were compared with data on delay time. There has been an increased use of shorter fractionation schedules in the period studied. Paradoxically, radical treatments have become longer. The average number of fractions for all patients was 17.4 and for palliative treatments it was 7.4. The monthly delay varied from 0 to 22 working days and the average was 7 working days. When fraction number was compared to treatment delay, there was a negative linear correlation (R = -0.25). The correlation was stronger (R = -0.467) when palliative treatments were compared, indicating that clinicians were more prepared to alter palliative treatments in the presence of a treatment delay than curative ones.

Dose Fractionation, Radiation↗

PubMed1982

High-dose fraction radiation therapy for intracranial metastases of malignant melanoma: a comparison with low-dose fraction therapy.

Malignant melanoma is considered unresponsive to conventional radiation therapy when it is delivered at a daily dose rate of 130--300 rad/fraction. Previous studies have suggested that this is in part due to a large shoulder on the radiation survival curve and that higher dose fractions might be beneficial. High-dose fraction therapy is effective for local control of cutaneous, lymph node, and soft-tissue metastases. Results in 46 patients treated with high- or low-dose fractions for intracranial metastases over the last decade in the Melanoma Unit and Department of Radiotherapy at Yale have been examined. Twenty-six patients received high-dose fraction therapy, generally 600 rad/fraction/week to 2400--3600 rad; 20 patients received low-dose fraction radiotherapy with 125--400 rad/fraction daily. All patients were given steroids, and most received chemotherapy. Results in both groups were similar. Comparison of high- and low-dose fraction patients revealed: improvement in 38 and 35%, respectively, stability in 23 and 25%, and deterioration in 38 and 40%. Median survival was three months in the high-dose fraction group and 2 1/2 months in the low-dose fraction group. Presence of hepatic metastases had no significant influence upon median survival in patients who received high-dose fraction radiotherapy. In patients receiving low-dose fraction, survival was 2 1/4 months with and three months without hepatic metastases. Death in most patients resulted from progression of central nervous system disease. Side effects, especially headache, were more prominent in the high-dose fraction group. However, in no instance did side effects require discontinuation of therapy. The greater ease of delivery for weekly high-dose fraction radiotherapy outweighed any other difference between the regimens.

Adult↗

PubMed1986

Sensitizers and radiation dose fractionation: results and interpretations.

Misonidazole is generally regarded as having been a clinical failure as a radiation sensitizer. It is hoped that the newer sensitizers SR-2508 and Ro 03-8799 will give better results because single dose studies with animal tumors have indicated that these two drugs give higher enhancement ratios than misonidazole at clinically tolerated doses. Other factors may also have influenced the clinical efficacy of misonidazole, however, particularly reoxygenation during the course of the fractionated treatments. In this paper reoxygenation in animal tumors and experimental studies in which fractionated radiation doses have been combined with sensitizers are reviewed. It is concluded that, even for dose fractions of 2 Gy, reoxygenation may not completely eliminate the influence of hypoxic cells on tumor response, when large total doses are given. Problems associated with tumor heterogeneity are also discussed to highlight the desirability of selecting the most suitable patients for clinical studies. Poorly reoxygenating tumors, rapidly growing tumors and tumors in patients in whom oxygen delivery to tissue is compromised are those whose control is most likely to be improved by combining radiation sensitizers with conventional treatment. However effective sensitizers should also allow fractionation schedules to be modified, to achieve a therapeutic gain, by taking advantage of differences in repair or repopulation between the tumor and critical normal tissue, without having to consider possible detrimental effects on reoxygenation.

Animals↗

PubMed1991

In vivo radiosensitizing activity of a new fluorinated hypoxic cell radiosensitizer, KU-2285, in combination with radiation dose fractionation.

Since most clinical radiotherapy is given as multiple small irradiation fractions, the present study was undertaken to test the in vivo radiosensitizing activity of a new hypoxic cell radiosensitizer, KU-2285, in combination with radiation dose fractionation. Radiosensitizing activity was measured by a growth delay assay using a transplanted mammary tumor in C3H/He mice, and by an in vivo-in vitro assay using the SCC VII tumor. KU-2285 was injected intraperitoneally 30 min before irradiation in all experiments. The in vivo-in vitro assay using SCC VII tumors showed that 12.5 micrograms/g of KU-2285 sensitized the tumors to irradiation (5 Gy/fr x 5 fr/48 hr or 6 Gy/fr x 3 fr/48 hr). KU-2285 also sensitized the transplanted mammary tumors to fractionated irradiation. We concluded that KU-2285 was able to sensitize two different murine tumors when given in combination with radiation dose fractionation.

Animals↗

PubMed1997

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

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 psychomotor 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.

Adult↗

PubMed1989

Cosmetic evaluation of breast conserving treatment for mammary cancer. 2. A quantitative analysis of the influence of radiation dose, fractionation schedules and surgical treatment techniques on cosmetic results.

The effects of surgical treatment techniques, radiation doses and fraction sizes on cosmetic outcome were analysed in a population of 161 patients with stage I and II breast cancer treated with breast conserving surgery and a wide range of radiotherapy doses. In 142 patients also quantitative measurements of nipple position asymmetries and breast contour retraction were carried out. The scoring and measurement results were analysed using a multivariate model to assess the relative importance of the various factors involved. In this material radiation dose to the breast was the most significant parameter correlated with cosmetic outcome (p = 0.0001). Radiation doses higher than 75 Gy in 37 fractions led to very poor results in more than 30% of patients. For the quantitative measurements of radiation fibrosis, a dose-response curve could be demonstrated over a dose range of 40 to 86 Gy in fraction sizes of 2 Gy. Above 50 Gy, increases in dose of 1 Gy correlated with an average displacement of nipple and breast contour of 1 mm, in upward direction and of 0.75 mm to the median. An increased amount of fibrosis was observed when part of the treatment was given in larger fraction sizes (4-6 Gy). Plotting the data against dose equivalent TE values, an alpha/beta value of 2.5 Gy could be estimated for the development of late fibrosis. Other treatment factors whose influence on cosmetic outcome could be identified and quantified were the differences in surgical techniques for the removal of the primary tumor (tumorectomy vs. segmentectomy, p = 0.05) and for the axillary clearance ("en bloc" dissection vs. separate incisions, p = 0.018). Also technical aspects of the radiotherapy on the regional lymph nodes, sometimes leading to matchline fibrosis, proved to be important (p = 0.0075). Finally, a number of tumor-related factors were assessed in order to take their relative importance into account, if necessary, when studying therapy factors. While tumor stage had only a limited impact in the range of tumors included in this study, the localisation of the tumor significantly influenced cosmetic outcome with worse results for inferior and medial localisations. While quantitative measurements were not correlated with all the factors identified for poor cosmesis, their great value is to quantify the radiation-induced fibrosis as well as the effects of different surgical techniques on nipple retraction.

Breast↗

PubMed1982

Randomized trial of conventional versus high fractional dose radiation therapy in the treatment of advanced head and neck cancer.

A prospectively randomized clinical trial was undertaken to compare conventionally fractionated radiation therapy and high fractional dose irradiation in the treatment of advanced, surgically unresectable head and neck squamous cell carcinoma. Sixty-four patients were entered into the study between 1973 and 1979 and were randomized to receive either 200 rad daily to total tumor doses of 6000-7000 rad in 6-7 weeks, or 400 rad daily to a total of approximately 4400 rad in 2-3 weeks. The distribution of patients between the two fractionation schedules was comparable regarding site of the primary tumor, extent of disease, degree of histologic differentiation and performance status. Twenty-nine of 31 (94%) patients in the 200 rad group and 29 of 33 (88%) in the 400 rad group has Stage IV disease. Twenty-six in the former group and 30 in the latter completed radiation therapy as planned. Acute skin and mucosal reactions occurred earlier in patients treated with 400 rad daily, but were of equivalent intensity and well within acceptable levels in both groups. No increase in late adverse effects was seen with high daily doses. Palliation of tumor-related symptoms and extent of tumor control were comparable in the two groups. Actuarial five year disease-free survival rates were approximately 10% in both treatment groups with a mean follow-up period of 5 1/2 years. We conclude that high fractional dose irradiation is equivalent to conventionally fractionated radiation therapy in the treatment of advanced head and neck cancer.

Aged↗

PubMed1989

[Autopsy cases of glioblastoma multiforme: treatment results of high-dose fractionated radiation therapy and CT scan findings].

Six autopsy cases of glioblastoma multiforme in cerebral hemisphere were examined by large histological preparations. They were treated by surgery and high-dose fractionated radiation therapy (5 Gy twice weekly). Their morphological changes were compared to the last CT and radiation field and total doses. Four out of six cases showed small residual tumor. One case showed extensive necrosis of the tumor and brain. The other case exhibited no tumor tissue at all. Spongy degeneration of the white matter associated with astrocytosis and macrophage infiltration extended sometimes beyond the local irradiation field. These white matter changes were easily occurred in the previous peritumoral edema where tumor cell infiltration was frequently observed. Residual tumor cells consisted of small anaplastic cells, which might be radioresistant and recur. Enhancement effect of CT scan showed tumor tissue and radiation necrosis with vascular proliferation.

Adult↗

PubMed1987

Low level X-radiation effects on carcinogenesis by 7,12-dimethylbenz(a)anthracene in Syrian hamster cheek pouch epithelium: acute vs fractionated radiation dose studies.

Studies examined the effects of acute and fractionated low to moderate level X-ray exposures on hamster cheek pouch carcinogenesis in vivo by 7,12-dimethylbenz(a)anthracene (DMBA). Animals were grouped by treatment as follows: acute doses of 0.85-3.40 Gy X rays; 17 once weekly doses of 0.01-0.20 Gy X rays (fractionated radiation); topical DMBA for 10 weeks; DMBA plus fractionated radiation starting together; DMBA plus acute radiation in Week 1 or 10 of DMBA treatments; and sham irradiation, DMBA vehicle, or anesthesia controls. After 44 weeks, hamsters were sacrificed, and their cheek pouches were excised, serially sectioned, and examined by light microscopy for histopathology. No histologic changes were observed in radiation-only hamsters. Carcinoma incidences in DMBA-only groups ranged from 45 to 60%. Carcinoma incidences were greater in groups receiving DMBA plus fractionated radiation than in groups receiving either acute radiation + DMBA or DMBA alone. Carcinoma incidences in acute radiation plus DMBA groups were lower than those in DMBA-only groups. These results suggest complex interactions between radiation and DMBA, perhaps with radiogenic cell killing being a principal factor in acute radiation + DMBA groups, and reciprocal additive or synergistic effects of radiation and DMBA on cancer induction and manifestation in fractionated radiation + DMBA groups.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1995

Single-dose compared with fractionated-dose radiation of the OM431 choroidal melanoma cell line.

PURPOSE: To compare single-dose and fractionated-dose radiotherapeutic effects on choroidal melanoma cells. METHODS: We determined the effects of gamma radiation on OM431 cell survival by exposing cells to either a single 9-Gy dose or two 4.5-Gy fractionated doses at intervals of 20 minutes to eight hours. The effects of single dosing and fractionated dosing at six hours were compared at doses of 2 to 12 Gy. RESULTS: Tumor cell repair was most rapid during the first two hours. Maximum repair had occurred by six hours after radiation. Cell survival curves showed doses greater than 3 Gy of single-dose gamma radiation resulted in a greater number of cells killed than did equivalent fractionated doses. CONCLUSIONS: Ocular melanoma in vitro is relatively radioresistant to low-dose fractionated radiotherapy. High single-dose radiotherapy would be more effective but would also result in more damage to normal tissue unless more focused modalities of radiotherapy are used.

Cell Survival↗

PubMed2000

Low dose fractionated radiation enhances the radiosensitization effect of paclitaxel in colorectal tumor cells with mutant p53.

BACKGROUND: The current study was undertaken to investigate the influence of wild-type or mutant p53 status on the radiosensitizing effect of paclitaxel in colorectal tumor cell lines. METHODS: HCT-116 (contains wild-type p53) and HT-29 (contains mutant p53) established from moderately differentiated colorectal carcinomas were used in this study. Colony-forming assay was performed after exposure to either different radiation doses (0.5-6 gray [Gy]) or paclitaxel (1-10 nM) or in combination. Induction of p53 and p21(waf1/cip1) by these treatments were determined by immunocytochemistry and Western blot analysis. RESULTS: Radiation caused an increase in nuclear p53 and p21(waf1/cip1) proteins in HCT-116 cells, indicating that p53 functionally induced p21(waf1/cip1). However, induction of nuclear p53 and p21(waf1/cip1) protein was not evident in HT-29 cells, suggesting that p53 was not functional in these cells. Survival data showed that the HCT-116 cells (survival fraction of exponentially growing cells that were irradiated at the clinically relevant dose of 2 Gy [SF(2)] = 0.383; dose required to reduce the fraction of cells to 37% [D(0)] = 223 centigray [cGy]) were significantly sensitive to ionizing radiation (P < 0.008) when compared with the HT-29 cells (SF(2) = 0.614; D(0) = 351 cGy). Paclitaxel caused a higher degree of clonogenic inhibition in HCT-116 (D(0) = 0.7 nM) than HT-29 (D(0) = 1.11 nM) cells (P < 0.06). When paclitaxel and radiation were combined, an enhanced radiosensitizing effect (P < 0.05) was observed in HCT-116 cells (SF(2) = 0.138; D(0) = 103 cGy), whereas in HT-29 cells no significant radiosensitization of paclitaxel was observed (SF(2) = 0.608; D(0) = 306 cGy). However, pretreatment with paclitaxel followed by multifractionated low dose radiation (0.5- or 1-Gy fractions for a total dose of 2 Gy) significantly enhanced the radiosensitizing effect in both HCT-116 and HT-29 cells. CONCLUSIONS: The results of the current study suggested that multifractionated radiation given at very low doses after exposure of cells to paclitaxel conferred a potent radiation sensitizing effect irrespective of p53 status.

Antineoplastic Agents, Phytogenic↗

PubMed1984

Treatment of advanced head and neck cancer: multiple daily dose fractionated radiation therapy and sequential multimodal treatment approach.

Fifty-eight patients with advanced head and neck cancer were entered into a randomised trial comparing chemotherapy (DDP + bleomycin) alone, multiple daily fractionated radiation therapy, and multimodality therapy consisting of chemotherapy plus multiple fractionated radiation therapy. Multimodal therapy gave a significantly higher response rate (69%) than either single-treatment modality. The use of a multiple daily dose fractionation allowed radiation therapy to be completed over 10 treatment days, and the addition of chemotherapy to the radiation treatment did not significantly increase toxicity. Patients receiving multimodal therapy also survived significantly longer (median 50 weeks) than those receiving single-modality therapy (median 24 weeks).

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1983

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

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.

Animals↗

PubMed1978

The effect of misonidazole in combination with radiation dose fractionation.

Single doses or multiple fractions of 2, 3, 5 or 10 Gy were given daily to KHT Sarcomas, growing in C3H mice, in combination with a misonidazole dose of 0.5 mg/g body weight administered 30--40 min before each radiation dose. Cell survival assays were performed on groups of tumours after different total doses to determine tumour cell survival curves for each fractionation schedule. The results indicate that misonidazole is effective in sensitizing the tumours to single doses and to large dose fractions, but that the degree of sensitization declines with fraction size such that there is no difference between the survival curves obtained for 2 Gy fractions given with or without prior drug treatment. Comparison of iso-effect curves, derived from the data, with those for normal skin suggests that, even though misonidazole increases the effect of the radiation on the tumour when large dose fractions are used, the small dose fractions probably still give a better "therapeutic ratio".

Animals↗

PubMed1995

Differential sensitivity of two predominant stromal progenitor cell subpopulations in bone marrow to single and fractionated radiation doses.

The sensitivity of fibroblastoid precursor cells in rat bone marrow to single and fractionated doses of gamma rays delivered in vivo was measured. In vitro colonies were classified as being compact or diffuse, and the progenitor cells for both types were slowly cycling in vivo (survival levels after exposure to hydroxyurea were 90 +/- 6% and 93 +/- 11%, respectively). The progenitor cells forming diffuse colonies were more resistant (D0 = 1.39 Gy) than those forming compact colonies (D0 = 0.76 Gy). The fractionation sensitivities were characterized by an alpha/beta ratio of 12.7 +/- 5.5 Gy for diffuse colonies and 4.5 +/- 3.0 Gy for compact colonies, respectively. The progenitor cells forming diffuse colonies may contribute more to long-term regeneration after high doses in vivo.

Animals↗