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L Voigtmann

Publications and source records attributed to L Voigtmann.

At least 19 recordsLinked to original sources
PubMed2000

Lack of effect of small high-dose volumes on the dose-response relationship for the development of fibrosis in distant parts of the ipsilateral lung in mini-pigs.

PURPOSE: Multi-field radiation therapy for intrathoracic tumours results in a heterogeneous dose distribution in lung tissue. This study investigated whether irradiation of small lung volumes with high fibrogenic doses affects the dose-response relationship for development of fibrosis in distant parts of the ipsilateral lung of mini-pigs. MATERIALS AND METHODS: The whole right lung of 26 'Mini-Lewe' pigs was irradiated with homogeneous doses of between 25 Gy and 40 Gy given in five equal fractions using opposing anterior-posterior portals and a linear accelerator. Another 32 animals were irradiated with a constant dose of 35 Gy to a small house-shaped high-dose field (base 3.0 cm, height 4 cm) located 3 cm caudolateral to the right hilus, while the surrounding right lung received either no irradiation or homogeneous doses of between 20 Gy and 30 Gy. The radiation fields were simulated and port films were obtained for each of the 10 fields in all pigs. Fibrosis was quantified 9 months after irradiation by determination of the hydroxyproline (HP) content of the 32 high-dose volumes and in the lung apex and the basolateral lung of all 58 pigs. Based on the reference value for the HP-ratio, i.e. the HP-concentration of the right lung over the left lung, obtained in 12 unirradiated control animals, the experimental results were converted into quantal data for probit analysis, a responder being an animal with an HP-ratio > 1.33. RESULTS: A dose-response relationship for the HP-ratio was obtained in the different lung sites and irradiation groups. For a given dose level the mean HP-ratios and response rates did not differ systematically between the lung apex and the basolateral lung. Probit analysis of the pooled data produced ED50 values of 21.8 Gy (95% CI 12-37) for irradiation without a high-dose volume and 25.9 Gy (24-28) for irradiation with a high-dose volume. These values are not significantly different. The results from both irradiation groups could be well fitted by a common dose-response curve with an ED50 value of 26.1 Gy. Unexpectedly, the response rates in the high-dose volume increased with increasing dose to the surrounding right lung. Analysis of the port films provided an explanation for this finding: inaccuracies in daily field positioning. When this error was corrected for by use of the mean dose to the high-dose volume, a dose-response curve with an ED50 of 25.2 Gy (22-29) was determined for the high-dose volume. CONCLUSIONS: The results of the study indicate that the irradiation of a small lung volume with high fibrogenic doses does not affect the dose-response relationship for development of fibrosis in distant parts of the ipsilateral lung.

Animals↗
PubMed1999

Response of pig lung to irradiation with accelerated 12C-ions.

The response of pig lungs to irradiation with 12C-ions was assessed in two experiments to validate the procedures for heavy ion therapy planning at the Gesellschaft für Schwerionenforschung (GSI) and to explore their range of applicability. In both experiments, the target volume (spread-out Bragg peak, SOBP) was planned to be a 4 cm long cylinder with a diameter of 4 cm. Doses in the SOBP were prescribed to be equivalent to 5x4 Gy, 5x5.5 Gy and 5x7 Gy of x-rays in the first experiment, and to 5 fractions of 7 Gy and 9 Gy in the second experiment. The lung response in the first experiment was less than expected on the basis of earlier experiments with photons. Pneumonitis reaction and chronic fibrotic changes were observed outside the prescribed high-dose region. In the second experiment, the effects were more pronounced than had been expected on the basis of the first experiment. Changes were most intense in the high-dose region, but were also seen throughout the lung along the beam channel. Moreover, significant skin reactions were observed at the beam entrance site in all animals and - less pronounced - at the beam exit site in 3 of the 6 animals. In conclusion, the complex irradiation geometry of the pig lung, the changes of body weight between the two experiments, and insufficient accounting for a change in the relative biological effectiveness (RBE) computation led to substantial deviations of the observed reactions from expectations, the reasons for which could be identified in a subsequent analysis. The less pronounced lung reaction in the first experiment was due to an overestimation of RBE in a preliminary version of the algorithm for its determination. The extension of the fibrotic reaction resulted from the smear-out of the high-dose region due to density variations in tissue structures, respiratory movement, and limited positioning accuracy. The skin reactions at the entrance port reflect the different treatment geometry in the two experiments. The one unexplained observation is the mild skin reaction that was observed in the second experiment at the beam exit site.

Animals↗
PubMed1997

Effect of irradiated volume on lung damage in pigs.

BACKGROUND AND PURPOSE: The volume dependence of radiation induced lung damage is of important clinical concern. The aim of the present study was to investigate the effect of irradiated volume on radiation pneumonitis and lung fibrosis in pigs after fractionated irradiation. MATERIALS AND METHODS: Twenty-five animals were irradiated with 10 x 14 cm2 fields to the whole right lung (about 530 cm3), while 19 animals received irradiation only to the lower part of the right lung (10 x 8 cm2 fields, about 260 cm3). The irradiations were given in five fractions over 5 days with total doses ranging from 14.3-38.0 Gy (whole lung) or 21.3-31.2 Gy (half lung) using a 60cobalt unit and an isocentric technique. Early lung damage was assessed during the first 8 weeks after the start of treatment by weekly chest radiographs and by twice weekly determinations of the breathing rate in resting animals. Fibrosis was quantified at autopsy (after 8 weeks or after 5-8 months) by histological evaluation and by determination of the hydroxyproline content of the lung tissue. Based on reference values obtained in 17 untreated control animals the experimental data were converted to quantals for probit analysis. RESULTS: The data did not indicate any significant differences for the incidence of lung damage after half lung and whole lung irradiation when injury was assessed by radiography, histology, or hydroxyproline content. However, using an increase in breathing rate as experimental endpoint, significant differences of radiation induced morbidity were observed. While none of the animals after half lung irradiation showed pathological breathing rates even after doses of 29 Gy and 31 Gy, a clear if shallow dose-response relationship with an ED50-value of 27 +/- 11 Gy (SD) was obtained after whole lung irradiation (P < 0.01). CONCLUSIONS: A volume effect can only be demonstrated for functional lung morbidity whereas induction of structural lung damage is independent of the volume irradiated.

Animals↗
PubMed1991

The hydroxyproline content in the lung tissue of young pigs after fractionated irradiation with photons or neutrons.

The radiation response of normal lung tissue was studied in 99 young pigs. Five fractions of Co-60-photons and of neutrons with an average energy of 6.2 MeV were applied during overall treatment times of five and 35 days respectively. The irradiation field comprised the whole of the right lung. At eight to ten weeks and at eight to 13 months animals were sacrificed and the removed lungs were investigated histopathologically and biochemically. Radiation induced fibrosis was evaluated by determining the ratio of hydroxyproline concentration of irradiated and non-irradiated lung in the same animal. Above a threshold there was a significant increase of the hydroxyproline ratio with increasing doses. Histopathological findings and hydroxyproline ratio were in close agreement. RBE values between 3.8 and 4.5 were calculated in accordance with the results using the other criteria of lung damage in our studies on pigs.

Animals↗
PubMed1990

[A universal verification and protocol system for teletherapy].

To increase the quality of radiotherapy a verify and record system (VPS) was developed for teletherapy equipments, that takes control of manually adjusted irradiation parameters and of recording all relevant data of radiotherapy. The VPS can be adapted to special wishes of the user and it lends itself to application on different irradiation equipments. In the represented paper especially the extent of efficiency of the system is shown which is characterized by high operating comfort, flexible reacting to exceptional cases and by high date and operating security. The testing phase on an accelerator model has been brought to a close, actually the system is installed to an electron linear accelerator "Neptun 10p" and led to clinical trial.

Humans↗
PubMed1990

[The determination of the RBE of neutrons based on the hydroxyproline concentration in the lung tissue of irradiated piglets].

To test the radiogenic reaction of normal lung tissue experiments were done in 99 young pigs altogether. The radiation field included the total right lobe of the lung, 5 fractions of photons or neutrons (mean energy 6.2 MeV) were applied in a total treatment of 5 or 35 days. After killing the animals and taking the lungs the examination of tissue samples and others has been done for contents of hydroxyproline (HP) that has been used to register radiogenic injuries where the relation of irradiated and non-irradiated half of the same animal was estimated as measuring value. Above a limit of 1.13 for the HP-quotient (estimated in non-irradiated controls) there was a significant correlation with dose. Between the results of HP-quotients and histopathological findings a very good correlation was found. Calculation of RBE was done from relation of the dose values of photons and neutrons on base of the same level of injuries. In the tested total dose limit (photons: 14.25-38 Gy, neutrons 3.0-8.5 Gy) RBE-values of 3.8-4.5 were reached that correlates well with other tested criteria of the study in young pigs.

Animals↗
PubMed1990

Application of a semi-phenomenological model to experimental data of radiation induced pneumopathy in pigs.

A semi-phenomenological model has been derived, which describes the inactivation effect on individual cells by survival curves. This model is applied to experimental data of pneumopathy in pigs. The corresponding survival curves as well as the relations between cell survival and complication probability are calculated and discussed. Furthermore, dose-response curves for single dose irradiation and different fractionation schemes are derived. The comparison between the response curve for single dose irradiation and similar curves from the literature shows a good agreement.

Animals↗
PubMed1988

[Children of parents irradiated prior to conception--a longitudinal study (results, 1986)].

The results of a longterm study on 55 children are presented whose parents were treated by radiotherapy. Five or ten years after a first examination, these children were submitted to a check-up investigation of their physical and intellectual development. The group of twenty irradiated fathers received an average dose to the gonads of 0.55 Gy (0.01 to 6.4 Gy), the group of twenty irradiated mothers 0.72 Gy (0.01 to 8.0 Gy). In all parents the most frequent finding was Hodgkin's disease, which was diagnosed as a neoplasm in 23 cases. Chemotherapy was applied in two out of 40 patients. The proof of paternity was made with a 86% accuracy for ten out of twenty fathers by determination of HLA types. A conception was demonstrated beyond all doubt after a dose to the testicles of 1.2 Gy in the irradiated fathers and after a dose to the ovaries of 3.0 Gy in the irradiated mothers. The offspring of the F1 generation showed no modification in the sex ratio. In the primary examination, a rate of 5.5% of severe malformations was found (trisomy E, bradyacousia of the inner ear, cleft hands and feet). 24% of the children had malformations which needed a treatment (hernias, torticollis, hip dysplasia). 18 out of 55 children (33%) presented abnormalities in the widest sense of the word. Three children (5.5%) were premature infants, and there is a general tendency towards shortened pregnancy (-3.6 days). Hernias (7/55) are a frequent finding. In children of both sexes, carporadiography shows a delayed development which is not compensated in the check-up examinations at five or ten years, but does not cause an underdevelopment in body height as compared to great normal collectives. The results suggest a slightly increased malformation rate among children whose parents were treated by radiotherapy. Above all the connective and supporting tissue seems involved. Some proposals are made how to give a radiogenetic advice to tumor patients who want to have children.

Abnormalities, Radiation-Induced↗
PubMed1987

[Repair mechanisms of the lung--experimental and clinical results].

The effect of dose and time and of the RBE on the pulmonary reaction to radiation has been studied by means of trials with young pigs. 70 animals received a fractionated (five and 15 fractions) telecobalt irradiation of the right lung over total treatment periods T of five, 23, and 35 days. The influence of dose and time on the pulmonary reaction to radiation is defined at the ED50 level (effective dose, after which 50% of animals will suffer from radiopathy) by a proportionality of D approximately N0.32 X T0.05. An alpha/beta value of 3.7 Gy is calculated according to the LQ model. An RBE value of 4.0 to 4.1 was determined in 38 animals treated over five and 35 days with the 6.2 MeV neutrons of the cyclotron Rossendorf. The experimentations on animals allow to classify the lung reaction as late effect. The clinical results found in literature show that this classification is also valid for human lung reaction to fractionated radiotherapy. So it is not possible to achieve a considerable increase of the pulmonary tolerance dose by increasing the total treatment period. The best sparing of the respiratory organ is obtained by an application of small single doses which allows to profit from the large repair capacity of pulmonary tissue. These results, as well as our considerations regarding the latent time between therapy and lung reaction, and some trials on laboratory rodents allow to speak of a radiogenic pneumopathy with the proprieties of a late reaction characterized by a pneumonitis appearing previously and changing into pulmonary fibrosis.

Animals↗
PubMed1986

Fractionated lung irradiation in young pigs with 6.2 MeV neutrons and cobalt-60.

Irradiations of the right lung with 6.2 MeV neutrons (38 test animals) and 60Co photons (34 test animals) were made using young pigs. Twenty animals were used as controls. Five fractions were administered in an overall treatment time of 5 or 35 days. The radiogenic pneumopathy was monitored with clinical, radiological and histological investigations, and by determining the hydroxyproline content in the lung tissue. The pneumopathy in pigs given neutrons developed after a shorter latency period and followed a more rapid and serious course than that in animals given gamma rays. While after photons the extension of the overall treatment time from 5 to 35 days led to a measurable but low increase of the ED50 this was not true for neutrons. The relative biological effectiveness (RBE) for the 6.2 MeV neutrons compared with 60Co photons was 4.0 for an overall treatment time of 5 days and 4.1 for 35 days.

Animals↗
PubMed1986

The time-dose relationship for radiation-induced lung damage in pigs.

The dose-time relationship of radiogenic pneumopathy was studied in 68 young pigs. The right lungs of the animals were irradiated by means of a telecobalt unit. Dose distribution calculations and the preparation and execution of irradiation were chosen to largely parallel the treatment of patients. The radiation response of the lungs was quantified by chest-X-rays, functional studies and histological and biochemical investigations of the autopsy specimens. The dose which produced unambiguous signs of radiation pneumopathy in at least 50% of the individuals (ED50), was used to draw an iso-effect plot. A steep slope of the iso-effect line was found when the number of fractions was increased from 5 to 15. In contrast, the iso-effect line showed only a small slope when the influence of overall time was investigated. Significant differences between doses for early and late reactions of the lungs could not be detected. The radiogenic lung reaction in pigs is adequately described by the relation D approximately N0.32 X T0.05 and an alpha/beta value of 3.7 Gy. These results are in a good agreement with those derived for mice by other investigators. The good comparability of the biological findings obtained with pigs to man points to the application of this dose-time relation in radiotherapeutical practice.

Animals↗