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Biomedical subjects

I Turesson

Publications and source records attributed to I Turesson.

At least 73 records · Page 4Linked to original sources
PubMed1990

Optimization of uncomplicated control for head and neck tumors.

Almost 200 patients have been treated for head and neck tumors at two different dose levels. Based on the clinically observed probabilities for tumor control and fatal normal tissue complications at the two dose levels, the dose giving maximum uncomplicated control has retrospectively been calculated and compared with the clinical data. A Poisson statistical model for control and complications has been used including a correlation parameter, delta, to describe the fraction of patients where control and complications are statistically independent. The clinically observed probability of uncomplicated tumor control, P+, is consistent with only a small fraction of the patients treated being statistically independent (delta = 0.2 or 20%). Customarily, 100% of the patients are assumed to be statistically independent with regard to tumor control and normal tissue complications. More precisely, the clinical data are consistent, with almost 20% of the patients being significantly more sensitive to radiation since they gain local tumor control but simultaneously suffer fatal complications. An even larger fraction of the patients (almost 30%) seemed to be more resistant to radiation, showing neither serious treatment complications nor control of the local tumor growth. It is suggested that if these patient groups could be identified by a predictive assay for the radiation sensitivity of their normal tissues and preferably also for their tumors, the uncomplicated tumor control could be increased by about 20%. This figure is based on the actuarial survival of the patients and has been corrected for the inevitable uncertainty in dose delivery. It is also pointed out that about 20% of the patients can never be saved by a predictive assay because of the considerable statistical variance associated with the Poisson process and the eradication of the last clonogenic tumor cell. Finally, note that the possible existence of radiation sensitive and resistant patient groups is consistent with known genetic deficiencies such as ataxia telangiectasia for the sensitive patients and the existence of repair efficient head and neck tumors that are unusually efficient in repairing double strand breaks. If such sensitive and resistant patient groups do exist, it should be sufficient to perform a predictive assay on normal tissues alone avoiding the often impossible task of sampling the most radiation resistant tumor cell line.

Carcinoma, Squamous Cell↗
PubMed1990

Individual variation and dose dependency in the progression rate of skin telangiectasia.

The progression rate of late skin telangiectasia after radiotherapy has been studied prospectively in patients for various fractionation schedules and dose levels. The degree of telangiectasia was scored on an arbitrary scale ranging from no detectable to totally confluent telangiectasia. Skin telangiectasia showed a progressive development at least up to 10 years. The rate of progression was strongly dose dependent. This finding has two important implications: the dose-latency relationship is steep, and the steepness of the dose-response relationship increases with the follow-up time. The most striking finding in this study was that the individual variation in progression rate was very large for the same treatment with a documented small variation in dose. For example, the latency for telangiectasia score 2 ranged between 17 and 90 months after 35 fractions of 1.8 Gy. The reasons for the large individual variation in progression rate are unclear and will be investigated further.

Breast Neoplasms↗
PubMed1990

Glottic laryngeal carcinoma with fixed vocal cord treated with full-dose radiation, total laryngectomy or combined treatment.

The results of the therapy of 46 patients with glottic squamous cell cancer with a fixed vocal cord and without regional lymph nodes (glottic T3N0) are reported. Primary surgery (total laryngectomy) in combination with preoperative irradiation gave significantly higher loco-regional control rate and survival rate than surgery alone. Primary radiotherapy with doses of 70 Gy or more and adequate follow-up was found to be an alternative to preoperative radiation and laryngectomy. The result of different treatment modalities speaks in favour of primary irradiation allowing preservation of the larynx and a good voice function. In case of recurrence salvage surgery with total laryngectomy is preferred.

Carcinoma, Squamous Cell↗
PubMed1990

Trisomy 14 in atypical chronic myeloid leukemia.

Trisomy 14 was the sole karyotypic anomaly in three patients with Ph1-negative chronic myeloid leukemia, and the only abnormality in one of three clones in a fourth case. The hematologic features were partly myeloproliferative, partly myelodysplastic, and included myeloid hyperplasia, neutrophilia without basophilia, a relatively high number of immature granulocyte precursors in the peripheral blood, and monocytosis in three and dysgranulopoiesis in two of the patients. These data, in combination with the patients' high age at diagnosis, their short survival, and the lack of rearrangements of the major breakpoint cluster region (M-bcr) in the two cases where cells were available for molecular analysis, indicate that all four patients suffered from atypical chronic myeloid leukemia (aCML). We suggest that trisomy 14 may be a characteristic karyotypic abnormality in this hematologic disorder.

Aged↗
PubMed1989

Analysis of late effects data using dose-response models: application to human skin telangiectasia data.

The clinical data for skin telangiectasia from previous prospective studies at the Radiotherapy Department in Gothenborg are reanalyzed using two dose-response models - the general formulations of the well known linear-quadratic (LQ) and NSD isoeffect models. Assuming that essentially no repopulation appears in the vessel endothelium for overall treatment times up to 68 days, the alpha/beta-value of 2.75 Gy is obtained for the LQ-model. The time factor is found not to be significant by the NSD-model for the treatment times used (less than or equal to 68 days) at the 95% level of confidence. The estimated value of the exponent of the number of fractions, A, is 0.321. The obtained values of the alpha/beta-ratio and of A show high sensitivity of the vessel endothelium to changes in the dose per fraction. Our results show that within the interval of the number of fractions used, 10-35 fractions, the NSD-model gives predictions comparable to those of the LQ-model. For number of fractions smaller than 5, a high discrepancy occurs between the two models, the NSD-model predicting higher values of the isoeffective total dose. The maximal deviation between the models appears for N = 1; 25% and 27% at the 5 and 50% level of effect, respectively. For large N and especially at low effect probabilities the NSD-model again predicts higher isoeffective doses: the dose predicted by the NSD-model for a regimen with 40 fractions and for 5% probability of telangiectasia is 7.5%, higher than that predicted by the LQ-model. Based on the estimated dose-response curves, considering the telangiectasia as the decisive late tissue effect, the requirement for the combined uncertainty in the dose delivery is estimated between 3 and 4.5%.

Dose-Response Relationship, Radiation↗
PubMed1989

The progression rate of late radiation effects in normal tissue and its impact on dose-response relationships.

The progression of late skin telangiectasia after radiotherapy has been studied prospectively in patients for 1, 2 and 5 fractions per week and various dose levels. The degree of telangiectasia was scored on an arbitrary scale. Skin telangiectasia was found to be a continuously progressing endpoint both in the individual patient and in terms of the number of patients who achieved a certain degree of damage. The rate of progression was dose-dependent. Dose-response analysis were performed at 3, 5 and 9 years follow-up for various endpoints: telangiectasia score greater than or equal to 1, score greater than or equal to 2 and score greater than or equal to 3. Iso-effective doses (ED50S) for score greater than or equal to 1 at 3 years, score greater than or equal to 2 at 5 years and score greater than or equal to 3 at 9 years were very similar. In an iso-effect analysis it is therefore worthwhile and time-saving to include the minimal detectable damage in the endpoint (e.g. using score greater than or equal to 1), even if this mild damage is of no clinical significance, and the dose in the endpoint (e.g. using score greater than or equal to 1), even if this mild damage is of no clinical significance, and the dose response become somewhat less steep than for more severe damage. The fact that the progression rate is dose-dependent has impact on dose-response analysis. Dose-response analysis for score greater than or equal to 3 at various follow-up times showed a very flat curve at 3 years compared to 5 and 9 years. The steepness of the dose-response curves was similar at 5 and 9 years. A minimum follow-up of 5 years is therefore necessary for reliable estimation of the late complication rates in a comparison of two dosage schedules using this endpoint. The implication of the continuous progression of telangiectasia is that the dose-response curves are shifted to the left with follow-up. The ED50 is dramatically reduced between 3 and 5 years. The ED50 is also significantly reduced between 5 and 9 years' follow-up, in spite of no change in the steepness of the dose-response curve during this period. Consequently, the time of response is the most fundamental parameter in any iso-effect analysis with progressive endpoints and the late complication rates always have to be specified at a fixed time of follow-up.

Dose-Response Relationship, Radiation↗
PubMed1989

Repair capacity and kinetics of human skin during fractionated radiotherapy: erythema, desquamation, and telangiectasia after 3 and 5 year's follow-up.

Prospective clinical fractionation studies on acute and late reactions in skin have been going on since 1972 at the Radiotherapy Department in Gothenburg. The clinical assay consisted of breast cancer patients irradiated postoperatively to the internal mammary nodes from unilateral or bilateral fields exposed to various dose schedules. 750 fields in 450 patients have been analysed. Schedules with 1, 2 or 5 fractions per week and 2 or 3 fractions per day were evaluated with erythema, desquamation and telangiectasia as endpoints. For some schedules a dose-response relationship was established in a limited dose range, but often there was only one dose group per schedule. These data are suited to analysis by the method of direct analysis of quantal response. This was used in the present analysis, along with the linear quadratic (LQ) model and its generalization, the incomplete repair (IR) model. The repair capacity was similar for erythema and desquamation, with alpha/beta ratios between 7.5 and 11.2 Gy. Unexpectedly, there was more significant time factor during radiotherapy courses up to 6 weeks for erythema and desquamation, but the repair capacity was changed after 4 weeks for both endpoints, and alpha/beta increased to between 18.3 and 34.5 Gy. The repair capacity for late telangiectasia differed significantly from that for erythema and desquamation, with alpha/beta values between 2.8 and 4.3 Gy. There was a significant time factor for telangiectasia with characteristic doubling time of about 16 days, when an exponential function for time was used. Concerning the repair kinetics in skin, there were insufficient data to obtain precise estimates, but there was a suggestion of two components of repair. This was inferred from higher-than-predicted recovery with 15-min intervals, when the data were fitted with the monoexponential model. The monoexponential fit gave t1/2 between 1.1 and 1.3 h for acute effects and 3.5 h for late effects. Recovery after 15-min fractionation intervals, if it resulted from a fast repair component, would be consistent with a half-time of 0.3-0.4 h. The time factor and the relative long half-time for repair for late effects have important implications for multiple-fraction-per-day treatment, and imply that interfraction intervals of 4 h or less, as commonly used, will be insufficient. Instead, intervals of 6 h or longer are recommended. Using accelerated fractionation with a significant reduction in overall treatment time a dose reduction is still necessary to take into account the time factor for late effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Breast Neoplasms↗
PubMed1989

Fractionation parameters for human tissues and tumors.

Time-dose factors such as fractionation sensitivity (alpha/beta) 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, alpha/beta is higher for acutely responding than for late-responding normal tissues. While many human tumors seem to be characterized by high alpha/beta 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.

DNA Repair↗
PubMed1988

Accelerated versus conventional fractionation. The degree of incomplete repair in human skin with a four-hour-fraction interval studied after postmastectomy irradiation.

A previously presented clinical assay with postoperative irradiation to bilateral parasternal fields in patients with breast cancer was used for a comparison of acute and late reactions in human skin after accelerated and conventional fractionation. Two and 3 fractions per day at 4-hour intervals were compared with one fraction per day. Dose fractions of about 2 Gy were used. Twenty-five fractions were given in 2.5, 1.5 and 5 weeks respectively. The acute reactions were similar regardless if 1, 2 or 3 fractions per day were given, i.e. equal total doses were isoeffective. The repair of intracellular damage was apparently completed within 4 hours. However, this might not be true due to a differential influence of proliferation and redistribution on the effect of different types of fractionation, which makes it difficult to interpret the result and estimate the degree of intracellular repair. The time to the acute peak reaction was shortened by 6 to 7 days with accelerated compared to conventional fractionation, explained by the differences in the dose delivery rates. Consequently, the onset of a compensatory proliferation is earlier after accelerated fractionation. Late reactions were more pronounced after accelerated than after conventional fractionation and 1 X 2.0 Gy/day was found to be equivalent to 2 X 1.80 Gy/day and 3 X 1.65 Gy/day at 4-hour intervals with an equal fraction number for all 3 schedules. Assuming that proliferation is negligible for late responding tissues, we interpret this finding as an expression of the degree of reduced intracellular repair. Finally, we would like to point out that the iso-effect dose relationships between acute and late reactions for accelerated versus conventional fractionation might vary, above all with the cell proliferation kinetics of acutely reacting tissue.

Breast Neoplasms↗
PubMed1987

Bone cell viability after irradiation. An enzyme histochemical study.

Adult rabbits were irradiated to one proximal tibial metaphysis while the contralateral tibia served as a control. Each animal was thus its own control. Single doses of 15, 25 and 40 Gy 60Co were used. The follow-up time was 11 to 22 weeks after irradiation. A histochemical method, recording diaphorase (NADH2 and NADPH2) activity in osteocytes, was employed. This method is regarded as superior to conventional histology. No evidence of osteocyte death was found even after 22 weeks following 40 Gy irradiation. This is interpreted as an indication that the osteocytes, which are end stage cells, are relatively radioresistant.

Animals↗
PubMed1987

A sulfhydryl-rich IgM protein with multiple serological specificities.

A monoclonal IgM lambda protein from a patient (E.T.) suffering from a lymphocytic lymphoma agglutinated Salmonella typhi bacteria and uncoated acryl particles. The antigenic determinant on Salmonella typhi bacteria was found to be 0-12 (alpha-D-Galp-(1-2)-alpha-D-Manp) while the structure on acryl particles recognized by IgM ET has not been defined. Both binding sites for bacteria and acryl particle determinants are localized on the same IgM molecule. The uncommon affinity of this IgM protein for some divalent heavy metal ions led to the finding of an unusually high content of sulfhydryl groups in the Fab portion of the molecule.

Acrylates↗
PubMed1986

The predictive value of skin telangiectasia for late radiation effects in different normal tissues.

Alterations in the microcirculation and parenchymal cell loss are common phenomena after irradiation of different organs. Whether parenchymal cell loss is a process well dissociated from vasculoconnective damage, or a consequence of this, is much debated. However, comprehensive radiopathological studies have shown that vasculoconnective tissue is an important common target for late effects in various organs. Scoring of skin telangiectasia was used by us as a clinical assay of late tissue effects after different dose schedules. All studies were done prospectively with standardized skin area, field size and radiation quality. The patients were scored regularly up to 10 years. The number of patients at risk for a prescribed score versus time was calculated with the life-table method. The late effects after 5 X 2.0 Gy/wk, in the dose range 40 to 70 Gy and after 2 X 4.0 Gy/wk, in the dose range 40 to 56 Gy have been established. The skin dose is 90% of the referred dose. Dose-response curves, relating the proportion of patients with a certain score at a fixed time and radiation dose and dose-latency curves, relating the latent period for a fixed proportion of patients with a certain score and radiation dose, were constructed. The analysis shows that: ED10/5 yr and ED50/5 yr for 5 X 2.0 Gy/wk is 50 Gy and 65 Gy, respectively, for distinct telangiectasia; The latent period, concerning both a certain frequency and degree of reaction, varies exponentially with dose level; The latent period for 50% of the patients, to obtain a certain score, LP50, is correlated to that for 10%, LP10, with LP50/LP10 = 2.2 +/- 0.2 (S.D.). This correlation is independent of score, total dose, and fractionation; Isoeffective doses for 5 X 2.0 Gy/wk and 2 X 4.0 Gy/wk, determined from the dose-response curves, resulted in the repair exp N between 0.31 and 0.32 and alpha/beta ratio between 2.9 and 3.1 Gy and determined from the dose-latency curves in exp N between 0.30 and 0.32 and alpha/beta ratio between 3.4 and 2.9 Gy. In conclusion, frequent and careful follow-up with registration of normal tissue reactions, until at least 10% of the patients have obtained the prescribed effect, is predictive for the further progression of the late effects. The fractionation characteristics for telangiectasia agree well with those for animal experimental morphological and functional endpoints for late effects in different organs and support the relevance of telangiectasia as a model for predicting late effects.

Breast Neoplasms↗
PubMed1985

Dose-response for bone regeneration after single doses of 60Co irradiation.

The Bone Growth Chamber (BGC) methodology was used to establish a dose-response relationship for regeneration of mature bone tissue after irradiation of 5, 8, 11, 15 and 25 Gy single dose 60Co. The BGC, which is a titanium implant, was inserted in the proximal tibial metaphyses, bilaterally, of a rabbit immediately following local irradiation to one tibia. Each animal thus served as its own control. During a healing period of 4 weeks, the two canals penetrating the implant became filled with more or less newly formed bone. At the end of the healing period, the implants were removed and taken apart and the newly formed bone was collected and its volume measured by microradiography and microdensitometry. It was found that in the dose range of 5 to 8 Gy bone regeneration was reduced by about 20% as compared to non-irradiated controls. Between 8 and 11 Gy, there was a critical range in that a small increase in dose resulted in a greatly reduced bone formation. At 11 Gy and above, the depression in bone formation, as compared to non-irradiated controls, was about 65 to 75%.

Animals↗
PubMed1985

Alterations in bone regenerative capacity after low level gamma irradiation. A quantitative study.

In the present study the influence of single 2.5 and 5 Gy doses of irradiation on the regenerative capacity of mature bone tissue has been investigated. To the knowledge of the present authors, no quantitative analysis of bone repair after low doses of irradiation has been presented previously. The experimental model used was the Bone Growth Chamber (BGC), which is a porous implant made of titanium. Each one of twenty animals was irradiated with 2.5 or 5 Gy to one tibial metaphysis. Directly after irradiation each animal had BGC:s inserted bilaterally into the tibial metaphyses. Thus, each animal served as its own control. Four weeks after irradiation the BGC:s were removed and the newly formed bone was collected from the implant pores and was analyzed by microradiography and quantified by microdensitometry and histology. It was found that 2.5 Gy irradiation led to no statistically significant alteration in bone formation as compared to non-irradiated controls. At the 5 Gy dose level, however, there was a significant reduction of bone formation as compared to non-irradiated controls.

Animals↗
PubMed1985

Normal tissue reactions to high dose-rate intracavitary irradiation of the vagina with different fractionation schedules and dose levels.

The radiation reactions in the normal tissues of the vagina, rectum and bladder were studied in 166 patients receiving prophylactic vaginal high dose-rate intracavitary irradiation. Most reactions were observed in the vaginal mucosa included in the intracavitary target and only a few in the rectum and bladder in close proximity to the same target. The influence of the total dose, the dose per fraction and the overall treatment time, summarized as the Cumulative Radiation Effect (CRE), correlated well to the rate of reactions after a correction of the formula for late effects.

Brachytherapy↗