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J V Lebesque

Publications and source records attributed to J V Lebesque.

68 records · Page 4Linked to original sources
PubMed1993

Lack of correlation of human fibroblast radiosensitivity in vitro with early skin reactions in patients undergoing radiotherapy.

Fibroblasts from breast cancer patients were obtained as outgrowths in vitro from punch biopsies and their radiosensitivity tested in early passages. Skin erythema reactions in the same patients were also measured, as degree of redness using reflectance spectrophotometry. Measurements were taken before and during a 4-week radiotherapy treatment with electrons to the thoracic wall. Of 59 biopsies studied, radiosensitivity and erythema were concurrently studied in 32. In 24, evaluable data from both clinic and laboratory were obtained. A population growth assay in 96-well plates, using absorption of sulphur rhodamine B as the stain for cell numbers, showed good agreement with the colony-formation assay. Plating efficiencies and growth rates in the colony assay were higher using human serum in place of foetal calf serum. Cell survival curves with human serum were mostly exponential with little shoulder. The parameters of survival at 2 Gy (SF2) and the dose required to give 10% survival (D10) were used in the correlations with clinical data; these were 0.25 +/- 0.09 and 3.03 +/- 0.50 Gy, respectively. There was a strong correlation between these two survival curve parameters (r = 0.98). Skin redness was found to linearly increase with time during radiotherapy. The slope of the increase differed markedly from patient to patient, with a range of a factor approx. 10. No correlation was found between SF2 and erythema response in the 24 evaluable patients (r = 0.13, p > 0.5). A similar lack of correlation was found using D10 as the radiosensitivity parameter (r = 0.12, p > 0.5). These data indicate that fibroblast radiosensitivity measured in vitro cannot be used to predict erythema reactions to radiotherapy in breast cancer patients.

Breast Neoplasms↗
PubMed1992

Maximizing setup accuracy using portal images as applied to a conformal boost technique for prostatic cancer.

A design procedure of a patient setup verification protocol based upon frequent digital acquisition of portal images is demonstrated with an application for conformal prostatic boost fields. The protocol aims at the elimination of large systematic deviations in the patient setup and includes decision rules which indicate when correction of the patient setup is needed. The decision rules were derived from the results of a theoretical and quantitative analysis of patient setup variations measured in three pelvic fields (one anterior-posterior and two lateral fields) of 105 fractions for nine patients. Deviations in the patient positioning, derived from one field, were quantified as two-dimensional (2-D) displacement vectors in the plane perpendicular to the beam axis by alignment of anatomical features in the portal and the simulator image. The magnitude of the overall setup variations along the anterior-posterior, superior-inferior and lateral directions varied between 2.6 and 3 mm (1 S.D.). Inter- and intra-treatment variations could be separated, both having equal magnitudes of 1.7 to 2.2 mm (1 S.D.). In addition, intra-treatment variations appeared to be predictable which was a prerequisite for the development of the decision rules. The 2-D setup deviations, measured in the three fields of one fraction were strongly correlated and a 3-D displacement vector was calculated. Utilization of this 3-D vector in a setup verification protocol may lead to an early detection of systematic setup deviations.

Analysis of Variance↗
PubMed1992

Postoperative radiotherapy for rectal and rectosigmoid cancer: the impact of total dose on local control.

Between 1984 and 1988, 206 patients were treated with pelvic radiotherapy after macroscopically complete surgery for rectal or (recto)sigmoid cancer. Depending on an estimation of the amount of small bowel in the intended treatment volume a total dose was, in general, 45 or 50 Gy. An additional boost of 10 Gy was given to 6 patients because of microscopically involved surgical margins. For tumor stage B a statistically significant trend (p = 0.017) for higher local control with higher total dose was observed comparing patients treated with a total dose of 45 Gy or less, with more than 45 Gy but less than 50 Gy or with a total dose of 50 Gy or more. This finding illustrates the impact of total dose on local control for postoperative radiotherapy for rectal carcinoma.

Adult↗
PubMed1991

The simultaneous boost technique: the concept of relative normalized total dose.

The simultaneous boost technique in radiotherapy consists of delivering the boost treatment (additional doses to reduced volumes) simultaneously with the basic (large-field) treatment for all treatment sessions. Both the dose per fraction delivered by the basic-treatment fields and by the boost-treatment fields have to be reduced to end up with the same total dose in the boost volume as in the original schedule, where the basic treatment preceded the boost treatment. These dose reductions and corresponding weighting factors have been calculated using the linear-quadratic (LQ) model and the concept of Normalized Total Dose (NTD). Relative Normalized Total Dose (RNTD) distributions were computed to evaluate the dose distributions resulting for the simultaneous boost technique with respect to acute and late normal tissue damage and tumor control. For the example of the treatment of prostatic cancer the weighting factors were calculated on the basis of the NTD for late normal tissue damage. For the treatment of oropharyngeal cancer the NTD for acute normal tissue damage was used to determine the weighting factors. In this last example a theoretical sparing of late normal tissue damage can be demonstrated. A second advantage of the simultaneous boost technique is that the megavoltage images of the large basic-treatment fields facilitates the determination of the position of the patient with respect to the small boost-treatment fields.

Dose-Response Relationship, Radiation↗
PubMed1991

Fast evaluation of patient set-up during radiotherapy by aligning features in portal and simulator images.

A new fast method is presented for the quantification of patient set-up errors during radiotherapy with external photon beams. The set-up errors are described as deviations in relative position and orientation of specified anatomical structures relative to specified field shaping devices. These deviations are determined from parameters of the image transformations that make their features in a portal image align with the corresponding features in a simulator image. Knowledge of some set-up parameters during treatment simulation is required. The method does not require accurate knowledge about the position of the portal imaging device as long as the positions of some of the field shaping devices are verified independently during treatment. By applying this method, deviations in a pelvic phantom set-up can be measured with a precision of 2 mm within 1 minute. Theoretical considerations and experiments have shown that the method is not applicable when there are out-of-plane rotations larger than 2 degrees or translations larger than 1 cm. Inter-observer variability proved to be a source of large systematic errors, which could be reduced by offering a precise protocol for the feature alignment.

Computer Simulation↗
PubMed1990

Dose-volume correlation in radiation-related late small-bowel complications: a clinical study.

The effects of the volume of irradiated small bowel on late small-bowel tolerance was studied, taking into account the equivalent total dose and type of pre-irradiation surgical procedure. A method was developed to estimate small-bowel volumes in the high-dose region of the radiation treatment using CT-scans in the treatment position. Using this method small-bowel volumes were measured for three-field and AP-PA pelvic treatments (165 cm3 and 400 cm3, respectively), extended AP-PA pelvic treatment (790 cm3), AP-PA treatment of para-aortic nodes (550 cm3) and AP-PA treatment of para-aortic and iliac nodes (1000 cm3). In a retrospective study of 111 patients irradiated after surgery for rectal or recto-sigmoid cancer to a dose of 45-50 Gy in 5 weeks, extended AP-PA pelvic treatment (n = 27) resulted in a high incidence of severe small-bowel complications (37%), whereas for limited (three-field) pelvic treatment (n = 84) the complication rate was 6%. These complication data together with data from the literature on postoperative radiation-related small-bowel complications were analysed using the maximum likelihood method to fit the data to the logistic form of the dose-response relation, taking the volume effect into account by a power law. The analysis indicated that the incidence of radiation-related small-bowel complications was higher after rectal surgery than after other types of surgery, which might be explained by the development of more adhesions. For both types of surgery a volume exponent of the power-law of 0.26 +/- 0.05 was established. This means that if the small-bowel volume is increased by a factor of 2, the total dose has to be reduced by 17% for the same incidence of small-bowel complications.

Carcinoma↗
PubMed1989

The lack of long-term recovery and reirradiation tolerance in the mouse kidney.

Mouse kidneys were bilaterally irradiated with X-ray doses of either 6 or 10 Gy (equivalent to approximately 30 and 70 per cent of full tolerance respectively). After an interval of 2 or 26 weeks the mice were retreated with a range of test doses given as single or fractionated irradiation schedules. Functional kidney damage was measured (using clearance of [51Cr]EDTA) before retreatment and at monthly intervals up to 1 year after retreatment. Reirradiation tolerance was assessed from dose-response curves for renal damage in retreated mice compared with that in age matched controls which received only the second treatment. Damage from the initial radiation doses progressed, leading to a decreased reirradiation tolerance with time. There was no evidence for any recovery from functional damage in the interval between 2 and 26 weeks. These studies would strongly suggest that reirradiation of a previously irradiated kidney (even after low initial doses below tolerance) is likely to lead to severe renal damage. Despite the poor reirradiation tolerance at 26 weeks, there was no reduction in the capacity for repair of sublethal injury when fractionated irradiation was given to previously irradiated mice compared with controls.

Animals↗
PubMed1988

Progressive development of radiation damage in mouse kidneys and the consequences for reirradiation tolerance.

The aim of this study was to investigate the influence of protracted overall treatment times on the development and repair of renal irradiation injury in mice. Functional kidney damage was measured, from the proportion of 51CrEDTA remaining in the plasma at 30 min after injection of the tracer. Damage was assessed at monthly intervals for up to 14 months after two equal doses of X-rays given in 1 day, 1 month or 6 months. There was no difference between the time of onset or rate of development of damage after two fractions in 1 day or 1 month, but there was a time lag of 7-15 weeks (depending on dose) before the development of damage after 2F given in 6 months. After this time lag the rate of progression of damage was the same for 2F/6 months as for 2F in the shorter intervals. There was therefore no indication of any increase in total tolerated dose for the kidney when the treatment time was protracted, although the time scales for onset of this damage differed. Tolerance of mouse kidneys to reirradiation at 6 months after single doses of 6-12 Gy was also assessed. All of the previously irradiated animals developed a more severe renal impairment after reirradiation than did the age-matched control mice. The most severe damage occurred in mice which received the highest initial radiation doses, but doses of only 6 Gy were sufficient to markedly reduce the tolerance to reirradiation. It was concluded from these studies that no additional dose-sparing (tissue recovery) took place in the kidneys during a 6-month interval. This was true even when the initial radiation dose alone was insufficient to cause measurable renal dysfunction.

Animals↗
PubMed1988

Reirradiation at long time intervals in mouse kidney: a comparison between experimental results and the predictions of the F-type tissue model.

The tolerance of a late-responding tissue to reirradiation after long time intervals has been analysed using the F-type tissue model. In this model the tissue is composed of identical cells, each of which is capable of extensive proliferation and of tissue-specific function. The model was adapted to calculate the response to two fractions of radiation given in a variable overall time. For two equal doses of radiation the repair of tissue damage after the first fraction could be detected theoretically by a change in the rate of cell depletion after retreatment and by an increase in the minimum cell number attained. For an 'experimental set-up', in which a constant first dose was followed by a range of retreatment doses in a variable overall time, the repair of tissue damage theoretically could be detected most sensitively by a shift of the dose-response curves to higher retreatment doses as the time interval between the two doses was increased. A prerequisite for a proper comparison of these dose-response curves was that the responses were evaluated at times after the first dose determined by the minimal latency times after high retreatment doses. From a comparison of these theoretical results with experimental findings for mouse kidneys it was concluded that no recovery of tissue function took place over a 6-month period. Instead it appeared that the kidneys had become more sensitive to irradiation over this period.

Animals↗
PubMed1986

Field matching in breast irradiation: An exact solution to a geometrical problem.

In radiation therapy of breast cancer several photon fields are used. Proper matching of the fields and minimizing the irradiated lung volume can be obtained by suitable beam blocking and appropriate angulation of the gantry, collimator and turntable. To facilitate the simulation procedure a new general method has been developed to calculate these angles, the position of the beam blocks and the field dimensions exactly.

Breast Neoplasms↗
PubMed1986

Analysis of the rate of expression of radiation-induced renal damage and the effects of hyperfractionation.

The response of mouse kidneys to multifractionation irradiation using the [51Cr]EDTA clearance method was re-analysed. As previously published, a series of schedules was investigated giving 1,2,4,8,16,32 and 64 equal X-ray doses in an overall treatment time of 3 weeks, using doses per fraction in the range of 0.9 to 17 Gy. The kidney function was assessed from 19 to 55 weeks after irradiation. The decrease of the clearance with time could be characterized by a new, relevant parameter: the relative rate constant for the development of late damage. These rate constants showed well defined dose-response relationships for each fractionation schedule with an estimated maximum rate constant of 0.15 wk-1. Making use of the logistic transformation of the relative rate constant data, the validity of the linear-quadratic (LQ) model was tested directly using proper statistical methods. We showed that only the higher fraction number data (16,32 and 64) could be described by the LQ-model (alpha/beta = 5.0 +/- 0.5 Gy). The deviations from the LQ-model could not be explained by incomplete or slow repair and we concluded that the expression of the clonogenic survival of target cells in the kidney is not sufficiently described by a linear and a quadratic term.

Animals↗
PubMedDate not supplied

Effects of 434 MHz microwave hyperthermia applied to the rat in the region of the cervical spinal cord.

Hyperthermia was applied in the region of the vertebral column between the cervical vertebrae 5 and thoracic 2, using a ring-shaped applicator operating at a microwave frequency of 434 MHz. This region was focally heated, including spinal cord, vertebrae, intervertebral discs and nerve roots. In all experiments temperature was measured at a 'reference' thermocouple probe which was placed against one of the cervical vertebrae 6, 7 or thoracic 1. Temperatures inside the vertebral canal were measured separately and proved to be below the 'reference' temperature: at 42 degrees, 43 degrees, 44 degrees and 45 degrees C (+/- 0.1 degree C) respectively the temperature in the canal was 41.2 degrees, 42.3 degrees, 42.9 degrees and 43.2 degrees C (+/- 0.4 degree C). Temperatures in tissues close to the vertebrae (e.g. within 2 mm lateral to the vertebrae, in the region of the brachial plexus) did not differ significantly from the temperature inside the canal. The temperature inside the intervertebral disc was as high as the 'reference' temperature. Temperatures measured at other sites, e.g. in the oesophagus, rectally and in the cervical muscles 5 or 10 mm lateral from the vertebral column showed that these sites were only slightly heated. The effects of hyperthermia at temperatures inside the spinal canal ranging from 41.2-43.2 degrees C for 30-120 min were investigated. One day after treatment at 41.2 degrees C for 120 min or 42.3 degrees C for 60 min neither neurological symptoms nor deaths were observed. Minor neurological symptoms were observed one day after 75 min at 42.3 degrees C. The incidence and severity of the neurological symptoms (ranging from unco-ordinated use of the forelegs to paralysis) increased with increasing temperature and duration of the hyperthermic treatment. Thermal damage even resulted in lethality: 74 per cent of the rats that died did so between 2 and 42 h after treatment. The LD50 value at 60 days at 43.2 degrees C was 30 min, at 42.9 degrees C, 41 min, and at 42.3 degrees C, 92 min. In most rats with neurological symptoms after treatment, recovery from motor dysfunctions took place within about two weeks. Even severe neurological symptoms which did not lead to lethality recovered completely. At day 60 no neurological symptoms were observed.

Animals↗