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At least 37 records · Page 2Linked to original sources
PubMed1986

Dose volume histogram analysis of liver radiation tolerance.

Eleven patients with carcinoma of the pancreas or biliary system received heavy charged particle radiation treatments and whole liver heavy charged particle radiation at Lawrence Berkeley Laboratory. Doses to the whole liver ranged from 10 to 24 Gray-equivalent (the biological equivalent of 10 to 24 Gray of low-LET photon radiation), whereas the dose to the primary lesion ranged from 53.5 to 70 Gray-equivalent (GyE). The fraction size was 2 to 3 GyE. The liver received partial as well as whole organ irradiation. Integral dose volume histograms for the liver were obtained in all 11 patients. An integral dose volume histogram displays on the ordinate the percentage of liver that was irradiated in excess of the dose specified on the abcissa. In this study, the clinical liver radiation tolerance of these patients is correlated with the information contained in an integral dose volume histogram. One patient developed radiation hepatitis. The integral dose volume histogram of this patient differed from the dose volume histograms of the other 10 patients. This difference was greatest in the range of doses between 30 and 40 GyE. Our results suggest that liver doses in excess of 30 to 35 GyE should be limited to 30% of the liver or less when 18 GyE of whole liver radiation is delivered at 2 GyE per fraction in addition to primary radiation of the pancreas or biliary system.

Helium↗
PubMed2000

Biological basis of radiation sensitivity. Part 1: Factors governing radiation tolerance.

Local tumor recurrence after radiation therapy is due primarily to the failure to eradicate all of the tumor cells within the treatment fields. Theoretically, all cancers could be controlled locally if a sufficiently high radiation dose could be delivered to a treatment volume that encompassed all of the tumor cells. In practice, however, the administration of a radiation dose high enough to sterilize all of the tumor cells would pose an unacceptably high risk of severe damage to normal tissues. Technologic improvements in the delivery of therapeutic radiation have led to some improvements in the therapeutic ratio (i.e., the ratio of the dose required to eradicate every tumor cell to the dose that produces unacceptable normal tissue toxicity). Further significant improvements in the therapeutic ratio will drive from an understanding of the mechanisms governing the sensitivity of malignant and normal cells to radiation. Part 1 of this two-part article reviews the clinical and tissue kinetic factors that govern the sensitivity of normal tissues and organs to ionizing radiation. Part 2, which will appear in next month's issue, describes recent insights into the cellular and molecular pathways that determine the sensitivity of normal cells and tumor cells to radiation.

Antineoplastic Agents↗
PubMed2004

Radiation tolerance of healthy tissues, high-LET beam particularities.

The sensitivity of healthy tissue is the limit of radiation therapy. Most of the technological progress of radiotherapy along its history have been devoted to improve the sparing of healthy tissues while increasing the tumor dose. The use of hadrons has been justified first for neutrons by radiobiological considerations (high RBE and no oxygen effect), then for protons by ballistic considerations (Bragg peak). Neutron ballistic is so unfavourable and side effects are so important when large and deep tumors are irradiated that their indications have been dramatically reduced and no recent studies on late effect after high RBE irradiation have been carried out. Therefore, the renewal use, hopefully on a large scale, of high RBE beam such as carbon ions, demands a new appraisal of the radiation tolerance of healthy tissues. From the photon and the neutron experience should be drawn: (i) the typology of late effect; (ii) the time schedule of the observation, (iii) the equivalent dose associated with observable late effects; (iv) dose limitations according to the type of tissues, the acceptable adverse effects, the security required and the RBE of the part of the beam irradiating the healthy tissues. Commune scale and description of the late effects will have to be decided. The biological mechanisms of late effects associating slow cellular lost, micro vascular failure and active fibrosis will need further investigation in the frame of high RBE irradiation.

Carbon↗
PubMed1994

[Radiation tolerance of the human spinal cord].

PURPOSE: Chronic myelopathy is among the most serious sequelae of high dose radiation treatment. Therefore medical and forensic reasons warrant detailed knowledge of the radiation tolerance of the human spinal cord. PATIENTS AND METHODS: This paper reviews published data on the incidence of radiation myelopathy in patients treated with megavoltage radiation. RESULTS AND CONCLUSIONS: Two years after completion of radiation treatment with daily fractions of approximately 2 Gy development of radiation myelopathy is expected in 1% of the patients at 50 to 55 Gy. An incidence of 5% is estimated to occur at approximately 55 to 60 Gy. At higher doses the risk of spinal cord damage increases steeply. Interpretation of these data has to consider that the incidence of radiation myelopathy increases with increasing time of follow-up. Even after two years no clearcut plateau is observed. High doses per fraction are poorly tolerated by the spinal cord, the alpha/beta-ratio appears to be approximately 1 Gy. Accelerated schedules with < or = 2 Gy per fraction but daily doses greatly exceeding 2 Gy may result in a higher risk of radiation myelopathy than conventionally fractionated treatments. This observation seems, at least in part, to be due to a slow component of repair of sublethal radiation damage in the spinal cord.

Humans↗
PubMed1992

Radiation tolerance and fractionation sensitivity of the developing rat cervical spinal cord.

To investigate the influence of age at irradiation on single dose radiation tolerance and fractionation sensitivity, the cervical spinal cord of rats was irradiated at the age of 1 week and at 15-18 weeks (adult). While the main histological lesions seem to be comparable after irradiation at the two ages, differences were found in single dose tolerance, latency to paresis due to white matter lesions, and fractionation sensitivity. The 50% effect dose (ED50) for single dose irradiation at one week was 19.5 Gy, which is only 10%, but significantly (p < 0.05), lower than the ED50 of about 21.5 Gy at 3 weeks and above. The latency to paresis was clearly influenced by the age at irradiation. The latency in the rats irradiated at 1 week was about 2 weeks, while for adult rats a latency of about 8 months was observed. The fractionation sensitivity for irradiation at 1 week was lower than the fractionation sensitivity of the adult rats; the alpha/beta value at 1 week was estimated to be 4.5 Gy, while for the adult rats an alpha/beta value of 1.8 Gy was found. As a consequence, the observed small difference in tolerance to single doses between 1 week-old and adult rats is further enhanced after fractionated irradiation. During prolonged irradiation treatments this decreased tolerance may be compensated by a higher proliferation rate in the immature central nervous system. The results of the present experiments indicate that, for a single tissue and endpoint, paresis due to white matter lesions in the rat cervical spinal cord, the latency to expression of damage and the fractionation sensitivity clearly change with age at irradiation.

Animals↗
PubMed1989

Treatment of CNS tumours with conventional radiotherapy: the importance of dose & volume factors in tumour control & CNS radiation tolerance.

Improved localisation of central nervous system (CNS) tumours resulting from newer diagnostic imaging techniques may allow the therapeutic irradiation of smaller volumes than currently practiced with the possibility of less normal tissue injury and/or the use of higher radiation doses. The influence of radiation dose and volume on the control rates for various types of CNS tumour and on the radiation tolerance of CNS tissue is imperfectly understood. Available data on these fundamental issues in the radiation treatment of CNS tumours is reviewed.

Brain↗
PubMed1987

[Radiation tolerance dose of the spinal cord following conventionally fractionated irradiation].

409 patients whose spinal cord were irradiated over 30 Gy with conventionally fractionated method were surveyed to study the relation between the dose of spinal cord and the incidence of radiation myelitis. Radiation myelitis was observed in 26 cases including 3 transverse myelitis ones. 5 year incidences of transverse myelitis calculated with life table method were approximately 0% at 40 Gy, 5% at 50 Gy, 10% at 60 Gy and 20% at 70 Gy. The radiation tolerance dose of the spinal cord was considered to be 50 Gy.

Adult↗
PubMed1995

Effect of intraperitoneal ATP on tumor growth and bone marrow radiation tolerance.

Transplants of a spontaneous murine fibrosarcoma (FSaII) treated with intraperitoneal ATP were studied in vitro, and in both C3H and nu/nu mice. Daily ATP treatment prolonged tumor volume doubling time in vivo and in vitro. Daily ATP treatments at the maximally tolerated dose (2 mmol/kg i.p.) did not significantly affect the pH or the PCr/Pi, or beta ATP/Pi ratios (measured by MRS). In contrast to the reduced tumor growth rate, there was no change in bone marrow recovery after whole body irradiation. ATP is minimally toxic to animals at active dose levels. It slows tumor growth rate without adversely affecting bone marrow radiation tolerance. ATP might therefore be useful as a biological modifier of chemotherapy or radiation therapy.

Adenosine Triphosphate↗
PubMed2003

Radiation tolerance of normal temporal bone structures: implications for gamma knife stereotactic radiosurgery.

Popular current thought states that hearing loss and facial weakness after radiosurgery of vestibular schwannomas is a function of cranial nerve damage. Although this may be true in some cases, the middle and inner ear contain rich networks of other sensitive structures that are at risk after radiotherapy and that may contribute to toxicity afterward. We reviewed the limited reported data regarding radiation tolerance of external, middle, and inner ear structures, and perspectives for therapy with gamma knife stereotactic radiosurgery are addressed.

Dose-Response Relationship, Radiation↗
PubMed1997

Radiation tolerance of the cochlear nerve at the gamma-knife in rabbits.

Since the first treatment of acoustic neurinoma using the gamma-knife by Leksell, a series of cases have been reported with good control rates. However, the most frequent complication is delayed hearing loss which occurs in more than 50% of patients. The purpose of this study was to define a safe dose by analyzing the radiosurgical dose-response relationship and histological effects on the normal cochlear nerve in rabbit. The rabbits had computed tomography (CT)-guided stereotactic radiosurgery on their cochlear nerves in the internal auditory canal with a 4 mm collimator focusing of a gamma-unit. Maximum doses of 10, 20, 30, 40, 60, 80, 100, 200 and 500 Gy were administered. After the radiosurgery, auditory brain stem responses (ABR) and the behavior of the rabbits were evaluated periodically. At the conclusion, histological investigations were performed. No physiological or histological findings were observed from doses of 30 Gy or below during the 12 month period after the radiosurgery. A dose of 100 Gy caused a severe ABR threshold elevation, vestibular dysfunction and facial palsy. Necrosis and demyelination of nerves were observed pathologically. In this study, we determined that the safe dose to the normal cochlear nerve during radiosurgery was under 40 Gy in rabbits, and complications seemed to vary due to individual differences in radiation tolerance.

Animals↗
PubMed2000

Radiation tolerance of rat spinal cord to pulsed dose rate (PDR-) brachytherapy: the impact of differences in temporal dose distribution.

PURPOSE: To investigate the impact of a time-variable dose rate during a high dose rate (HDR-) or pulsed dose rate (PDR-) brachytherapy fraction with the HDR-microSelectron and to compare this with the biological effect of a constant dose rate treatment with the same average dose rate (as in the case of (192)Ir-wires). Moreover, the kinetics of repair in rat spinal cord are investigated using a wide spectrum of temporal dose distributions. MATERIALS AND METHODS: Two parallel catheters are inserted on each side of the vertebral bodies of the rat spinal column (Th(10)-L(4)) and connected to the HDR-microSelectron. Interstitial irradiation (IRT) is performed with a stepping (192)Ir-point source, varying the activity of the point source between 0.3 and 6.5 Ci. Three different groups of experiments are defined, varying the overall treatment time and average dose rates in the range of 3-8, 28-53 and 82-182 min and 312-489 Gy/h, 32-56 Gy/h and 13-15 Gy/h, respectively. Difference in temporal dose distribution (dose rate variation) during almost the same overall treatment time is obtained by varying the number of pulses per dwell position in either one or ten runs through the implant. For reasons of comparison, previously reported results of continuous irradiation at a constant dose rate obtained with two (192)Ir-wires in a fixed position are reanalyzed. Paralysis of the hindlegs after 5-6 months and histopathological examination of the spinal cord of each animal are used as experimental endpoints. RESULTS: During one run of the (192)Ir-point source, the peak dose rate is at least 25 times higher as compared with the minimum local dose rate and almost four times higher as compared with the average dose rate. For the three different groups of varying overall treatment times and average dose rates there is a significant difference in biological effect, with an ED(50)-value of 23.1-23.6 Gy (average dose rate 312-489 Gy/h), 25.4-27.9 Gy (average dose rate 312-489 Gy/h) and 29.3-33 Gy (average dose rate 13-15 Gy/h). For these range of single doses, difference in temporal dose distribution with either one or ten runs is only significant for treatment times less then 1 h. For the prolonged treatment times at lower average dose rates, the difference between one or ten run is no longer significant. However, the results with the (192)Ir-point source at an average dose rate/run of 13-15 Gy/h are significantly different from the ED(50)-value of 33 Gy using (192)Ir-wires at the same but constant dose rate. Using different types of analysis to estimate the repair parameters, the best fit of the data is obtained assuming biphasic repair kinetics and a variable dose rate (geometrically dependent) for the (192)Ir-point source. On the basis of the incomplete repair LQ model, two repair processes with an alpha/beta ratio=2.47 Gy and repair halftimes of 0.19 and 2.16 h are detected. The partition coefficient for the longer repair process is 0.98. This results in the proportion of total damage associated with the longer repair halftime being 0.495 for short sharp fractions with complete repair in between. CONCLUSIONS: Even in the range of high dose rates of 15-500 Gy/h, spinal cord radiation tolerance is significantly increased by a reduction in dose rate. For larger doses per fraction in PDR-brachytherapy dose rate variation is important, especially for tissues with very short repair half times (components). In rat spinal cord the repair of sublethal damage (SLD) is governed by a biphasic repair process with repair halftimes of 0.19 and 2.16 h.

Animals↗
PubMed1997

[Radiation tolerance of patients after pneumonectomy for bronchial cancer: role of pulmonary function tests].

Radiation is often necessary after pneumonectomy, either immediately or due to local cancer recurrence. High radiation doses represent a challenge due to the limited tolerance of the lung and the necessity of preserving and protecting the remaining lung parenchyma. The use of CT scan based-treatment planning allows delivery of high radiation doses. To evaluate the radiation tolerance of the lung after high radiation dose, we compared pulmonary function tests performed before surgery and after radiation therapy. Ten male patients (mean age, 56 years old; age range, 45-73) were irradiated after pneumonectomy for lung cancer. All patients had a CT scan-based treatment planning. The mean radiation dose was 56 Gy (45-66 Gy) delivered with a linear accelerator and multiple complex fields. Two or more sets of pulmonary function tests were available (before surgery and 2 to 6 months after radiation). No patient developed clinical radiation pneumonitis and most of the patients had a minimal paramediastinal fibrosis at CT scan. Postirradiation pulmonary lung tests were compared to the theoretical values of the estimated defect observed after pneumonectomy. No significant decrease in forced expiratory volume in 1 s/inspiratory vital capacity (FEV1/IVC) was observed in ten evaluable patients; the observed values were comparable to those expected after pneumonectomy without irradiation (FEV1/IVC: 61 to 100%), showing that irradiation did not alter pulmonary function. Computerized tomography-based treatment planning and the use of complex beam positioning allowed optimal lung parenchymal preservation. Through this procedure, high doses of radiation can be delivered to the mediastinum and bed tumor. Comparison of pulmonary function tests performed before surgery and after radiation showed no alteration of lung function, even after high doses. Optimal tools required for the evaluation of radiation on lung parenchyma are still to be defined.

Aged↗
PubMed2003

Radiation tolerance of functioning pituitary tissue in gamma knife surgery for pituitary adenomas.

OBJECTIVE: This study is intended to contribute to a determination of the sensitivity of preserved hypophyseal function to focal radiation in pituitary adenomas. METHODS: We compared two subgroups of patients followed up for a median of 5 years after gamma knife surgery (GKS). Subgroup 1 (n = 30) showed postirradiation hypopituitarism. Subgroup 2 (n = 33) was continually eupituitary. These subgroups were taken from a previously published study relating to a larger group of 163 patients with pituitary adenomas treated by GKS and evaluated after a median follow-up period of 2 years. A relatively high treatment dose was used in this larger group (median, 20 Gy to the tumor margin for growth control in nonfunctioning adenomas; median, 35 Gy for hypersecreting adenomas). Early results approached those of microsurgery, and there were only a few side effects. In the present study, we compared 16 different variables in the same two subgroups to discover the relationships that caused a delayed appearance of postirradiation hypopituitarism. The main pretreatment and treatment parameters were measured on reconstructed treatment plans. This database was used for statistical evaluation. RESULTS: The relationship between the mean dose and the volume of functioning hypophysis was stronger in terms of worsening of pituitary function than that of the spot dose to different intrasellar structures. We found that for our group of patients, the safe mean dose of radiation to the hypophysis was 15 Gy for gonadotropic and thyrotropic functions and 18 Gy for adrenocorticotropic function. The worsening of pituitary function was also significantly dependent on the dose to different anatomic levels of the infundibulum, but we did not succeed in fully characterizing this relationship. In addition, we discovered significant levels of dependency of postirradiation pituitary damage to different pretreatment and treatment variables. CONCLUSION: Knowledge of the radiation tolerance of functioning pituitary structures subjected to GKS can ensure better preservation of pituitary function after irradiation. This is valid for the group of patients we studied. Our study's findings can be used as a guideline for GKS treatment of new patients with pituitary adenomas, and it can serve for comparison with the experience of other gamma knife centers.

Adenoma↗